Essentials of Pediatric Oral Pathology Mayur Chaudhary, Shweta Dixit Chaudhary
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Developmental Disturbances in ChildrenChapter 1

Mayur Chaudhary,
Shweta Dixit Chaudhary,
Prashant Dixit
 
INTRODUCTION
Developmental disturbances comprise a group of disorders that are manifested during the early months of gestation. They may be genetically determined, environmentally determined or may exhibit a role of both genetic and environmental factors. These disorders may resolve after few months or may persist forever. The disorders may be termed congenital when present at birth and hereditary when transmitted from one generation to another. Special attention is to be given to the term anomaly which means irregularity or different from normal.
This chapter focuses on some of the developmental disturbances and anomalies pertaining to children.
 
DEVELOPMENTAL DISTURBANCES OF JAWS
  • Agnathia
  • Micrognathia
  • Macrognathia
  • Facial hemihypertrophy
  • Facial hemiatrophy.
 
AGNATHIA
 
Definition
A lethal anomaly characterized by hypoplasia or absence of the mandible with abnormally positioned ears and any form of holoprosencephaly (Fig. 1.1).
 
Etiology
  • May be due to autosomal recessive inheritance.
  • Sporadic cases without inheritance have also been seen.
 
Pathogenesis
Agnathia probably results due to failure of migration of neural crest mesenchyme into the maxillary prominence at the fourth to fifth week of gestation (post-conception). When it is not associated with central nervous system malformations it is referred to as “agnathia-microstomia-synotia.”
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FIGURE 1.1: Agnathia showing ears fused in the midline, complete absence of the mandible and clefting of both lips
 
MICROGNATHIA
Micrognathia implies a small jaw and may affect either the maxilla or mandible. Lannelongue and Menard first described Pierre Robin syndrome in 1891 in a report on two patients with micrognathia, cleft palate and retroglossoptosis.1 In 1926, Pierre Robin published the case of an infant with the complete syndrome.2 Until 1974, the triad was known as Pierre Robin syndrome; however, the term syndrome is now reserved for those errors of morphogenesis with the simultaneous presence of multiple anomalies caused by a single etiology.
 
Pathogenesis
  • Autosomal recessive inheritance is possible. An X-linked variant has been reported involving cardiac malformations and clubfeet.3
  • Acquired type of micrognathia is of postnatal origin and usually results from a disturbance in the area of the temporomandibular joint. Trauma and infection may lead to ankylosis of the joint which may result in varying degrees of micrognathia.
  • Three pathophysiological theories exist to explain the occurrence of Pierre Robin sequence.
    1. The mechanical theory: This theory is the most accepted. The initial event, mandibular hypoplasia, occurs between the 7th and 11th week of gestation. This keeps the tongue high in the oral cavity, causing a cleft in the palate by preventing the closure of the palatal shelves. This theory explains the classic inverted U-shaped cleft and the absence of an associated cleft lip. Oligohydramnios could play a role in the etiology since the lack of amniotic fluid could cause deformation of the chin and subsequent impaction of the tongue between the palatal shelves.
    2. The neurological maturation theory: A delay in neurological maturation has been noted on electromyography of the tongue musculature, the pharyngeal pillars and the palate, as has a delay in hypoglossal nerve conduction. The spontaneous correction of the majority of cases with age supports this theory.
    3. The rhombencephalic dysneurulation theory: In this theory, the motor and regulatory organization of the rhombencephalus is related to a major problem of ontogenesis.
 
Clinical Features
  • This heterogeneous birth defect has a prevalence of approximately 1 per 8500 live births.
  • The male-to-female ratio is 1:1, except in the X-linked form.
  • Micrognathia is reported in the majority of cases (91.7%). It is characterized by retraction of the inferior dental arch, 10 to 12 mm behind the superior arch (Fig. 1.2).
  • The mandible has a small body, obtuse gonial angle, and a posteriorly located condyle. The growth of the mandible catches up during the first year; however, mandibular hypoplasia resolves and the child attains a normal profile approximately by the age 5 to 6 years.
  • However, due to posterior positioning of the mandible with regard to the skull, retrusion of the jaw may be apparent.
  • Glossoptosis is noted in 70 to 85 percent of reported cases. Macroglossia and ankyloglossia are relatively rare findings.
Since the frequency of diagnosis of macrognathia, facial hemihypertrophy and facial hemiatrophy is less in the pediatric population and are generally diagnosed in adulthood, these have not been explained in detail here.
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FIGURE 1.2: Micrognathia showing an underdeveloped mandible
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FIGURE 1.3: Congenital lip pits on the lower lip
 
DEVELOPMENTAL DISTURBANCES OF LIPS AND PALATE
  • Congenital lip pits and fistula
  • Commissural lip pits
  • van der Woude syndrome
  • Cleft lip and cleft palate
  • Cheilitis glandularis
  • Cheilitis granulomatosa
  • Peutz-Jeghers syndrome
  • Labial and oral melanotic macule
 
CONGENITAL LIP PITS AND FISTULA
Congenital lip pits and fistula may occur due to notching of the lip at an early stage of development with fixation of tissue at the base of the notch.
 
Clinical Features
  • They may be unilateral or bilateral.
  • Most commonly occur on the lower lip (Fig. 1.3).
  • Sometimes, a mucous secretion may exude from the base of the pit which may be due to saliva from minor salivary glands draining into the depth of the invagination.4
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FIGURE 1.4: Bilateral congenital lip pits at the commissural area
 
COMMISSURAL LIP PITS
These are mucosal invaginations occurring at the corners of the mouth on the vermillion border.
 
Pathogenesis
  • They follow a hereditary pattern and may occur alone or in association with other developmental anomalies most possibly following a Mendelian dominant inheritance.
  • They mostly occur due to incomplete/failure of normal fusion of maxillary and mandibular processes.
 
Clinical Features
  • Taylor and Lane, 1966,3 and McConell, 1970,4 reported that 75-80 percent of the cases of lip pits were associated with cleft lip or cleft palate.
  • Commissural lip pits are same as congenital lip pits but occur at the lateral commisures of lip (Fig. 1.4).
  • Prevalence in children ranges from 0.2 to 0.7 percent.5
  • They may be unilateral or bilateral.
  • Most commonly occur at the corners of the mouth.
  • Sometimes, a mucous secretion may exude from the base of the pit which may be due to saliva from minor salivary glands draining into the depth of the invagination.
 
Histopathologic Features
  • Lesional area shows a narrow invagination lined by stratified squamous epithelium.
  • Few areas show ducts of minor salivary glands.
 
VAN DER WOUDE SYNDROME
van der Woude syndrome (VWS) is an autosomal dominant syndrome, single gene disorder showing high penetrance and variable expressivity that typically consists of a cleft lip or cleft palate and/or distinctive pits of the lower lips. It was characterized in 1954.6
 
Etiopathogenesis
  • This is an autosomal dominant syndrome with a penetrance of 75 percent. But penetrance was recorded to be 100 percent when supposedly unaffected carriers were closely examined for minor expressions of the syndrome.
  • Viral infections may result in an interference with the IRF6 gene which is involved in the immune response to viral infections.
  • De novo mutations may lead to single nucleotide polymorphism resulting in a defect leading to the features of van der Woude syndrome.
  • The gene isolated for van der Woude syndrome is 1q32 to q41.
  • A second modifying gene is 17p11.2-p11.1 with a second chromosome locus being 1p34.
  • The Interferon Regulatory Factor-6 (IRF-6) is the specific gene responsible for VWS. This gene has been found to regulate fetal craniofacial development in mice.
 
Clinical Features
  • Lower lip pits
  • Incomplete unilateral cleft lip
  • Cleft lip with or without cleft palate
  • Bilateral cleft lip and palate (Fig. 1.5)
  • Isolated cleft palate
  • Submucosal cleft palate
  • Bifid uvula may occur as an isolated finding
  • Cleft lip and palate
    • Cleft lip and palate may be isolated, unilateral or bilateral.
    • Submucous cleft palate leads to hypernasal voice.
  • Lip pits
    • Lower lip pits are fairly distinctive and usually medial.
    • May be associated with accessory salivary glands.
    • Saliva, either visible or expressible, may be present.
    • Lip pits, at times, could be the only manifestation of the syndrome.5
    zoom view
    FIGURE 1.5: Bilateral cleft lip in van der Woude syndrome
  • Teeth
    Individuals may have hypodontia, most commonly manifested as missing maxillary lateral incisors or maxillary or mandibular second premolars. Again, this may be the only manifestation of the syndrome.
  • Other oral manifestations:
    • Syngnathia (congenital adhesion of the jaws).
    • Narrow, high arched palate.
    • Ankyloglossia (short glossal frenulum or tongue-tie).
  • Extraoral manifestations:
    • Limb anomalies
    • Popliteal webs
    • Brain abnormalities
    • Accessory nipples
    • Congenital heart defects
    • Hirschsprung disease
  • Features of van der Woude syndrome have been seen in individuals with popliteal pterygium syndrome, which has also been linked to mutations in the same gene.
 
CLEFT LIP AND CLEFT PALATE
Millions of children and adults suffer from the social enigma of cleft lip and palate, battling to live a life of dignity. Failure of fusion of palatal shelves, septum and primary palate, which normally takes place between the 8th and 17th week of embryologic development leads to the formation of a cleft.
 
Development of Palate
The organization of the face requires tissues to proliferate, fuse and differentiate. The polarizing signal candidates expressed in craniofacial primordia include sonic hedgehog (shh), its putative receptor patched, fibroblast growth factor 8 (FGF-8) and bone morphogenetic protein 2 (BMP-2).7 Evidence exists that the teratogen, retinoic acid exerts some of its effects on craniofacial development through the disruption of the shh signaling pathway. Transforming growth factor -3 (TGF -3) also has a broad spectrum of biological activities. 6
In humans, palate development begins towards the end of the fifth week of intrauterine life and is complete at about twelve weeks. The critical period is from the end of the sixth week to the beginning of the ninth week. In normal palate development, mesenchymal cells from the neural crest migrate to the primitive oral cavity forming the maxillary processes in association with the craniopharyngeal ectoderm.8
The primary palate arises from the fusion of two medial nasal prominences that form the intermaxillary segment, which develops towards the end of the fifth week of intrauterine life in humans. It consists of two portions: a labial component that forms the philtrum of the upper lip and a triangular palatal component of bone that includes the four maxillary incisor teeth. The primary palate extends posteriorly to the incisive foramen. In humans, the secondary palate comprises at least 90 percent of the hard and soft palates. Development of the intact secondary palate is a dynamic process which has been arbitrarily split into three stages. Stages I to III namely Figs 1.6 and 1.7). Stage I of secondary palate development is characterized by formation of the palatal shelves from the maxillary processes. These shelves are orientated vertically, either side of the developing tongue. It is not known why the shelves attain this vertical orientation. Ferguson, 1981, proposed that the direction of shelf growth be related to the amount of space available in the oronasal cavity during the period of palatogenesis.9
At a precise developmental stage (Stage II), these vertical palatal shelves elevate to a horizontal position above the dorsum of the tongue.10 This event occurs rapidly, possibly in a matter of hours.
Stage III of secondary palate development involves fusion of the medial edge epithelium (MEE) of the approximating palatal shelves with each other via numerous desmosome contacts to form a midline palatal seam. This then separates the oral and nasal cavities. Keratin fibrils and desmosomes are upregulated in the medial edge epithelium seam at this point, presumably to strengthen the bond between the newly adherent medial edge epithelium cells. This seam rapidly degenerates, a process characterized by loss of complex cytokeratins and basement membrane components such as laminin and desmosomes and by an increase of vimentin-rich connective tissue, tenascin, proteoglycan and collagen expression. Medial edge epithelium degeneration allows mesenchymal cells to flow across the now intact horizontal palate. There have been several theories on the mechanism(s) of medial edge epithelium degeneration. Shapiro and Sweney, 1969, suggested that it occurred as a result of programmed cell death.11 Gartner et al, 1978, disputed this on the grounds that there was no evidence of any cellular debris or phagocytic activity at any time during this process.12 Furthermore, some evidence of metabolic activity occurring within so-called apoptotic cells was described. A radical postulate by Fitchett and Hay, 1989, offered the possibility that the medial edge epithelium cells migrate into the body of the mesenchyme and transform into mesenchymal cells.13. This process is known as epithelial-mesenchyme transformation (EMT). An alternative view is that medial edge epithelium cells migrate nasally and orally out of the medial edge epithelium seam and become incorporated into the oral and nasal epithelia on the palatal surface.
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FIGURE 1.6: Schematic diagram of coronal section through a developing face showing three stages of secondary palate development. At stage I, the palatal shelves are vertical, they elevate in stage II and fuse in stage III
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FIGURE 1.7: Hematoxylin and eosin stained section of a developing fetus where the palatal shelves have elevated with the tongue lying inferiorly. Although there has been elevation, the shelves have still to fuse
7
On completion of stage III, the epithelia on the nasal aspect of the palate are pseudostratified ciliated columnar cells whilst those on the oral aspect of the palate are stratified squamous, non-keratinizing cells.
Cleft palate may result from disturbances at any stage of palate development like defective palatal shelf growth, delayed or failed shelf elevation, defective shelf fusion, failure of medial edge epithelium cell death, post-fusion rupture and failure of mesenchymal consolidation and differentiation. Sun et al, 1998a, suggested that lack of intimate palatal shelf contact after elevation is one possible cause and recent research into palate development has concentrated on fusion of the shelves rather than elevation.14 Ferguson, 1981, on the other hand, took the view that failure of palatal shelf elevation may be responsible for 90 percent of palatal clefting.
Palatal shelf elevation: In principle, an intrinsic force generated within the palatal shelves reaches a threshold level which exceeds the force of resistance culminating in shelf elevation. Elevation of the palatal shelves is rapid with a swinging ‘flip-up’ mechanism in the anterior one-third of the palate and an oozing remodeling ‘flow’ mechanism in the posterior two-thirds of the palate.
 
Etiopathogenesis
  • Isolated clefts are those that are associated with no other birth anomaly.
  • Syndromic clefts are those associated with other birth disorders.
  • Clefts are a feature of over 660 syndromes and most are rare.
More common syndromes: Pierre-Robin sequence, Crouzon, Apert, Pfeiffer, van der Woude, Treacher Collins, Velocardiofacial. Syndromal clefts makes up 15 percent of cleft lip +/– palate.
Isolated clefts are caused by an interaction between an individual's genes and certain environmental factors (often impossible to identify). Phenytoin, accutane, alcohol, tobacco, folic acid and pyridoxine deficiencies have also been associated with clefting.15
Increasing parental age, especially an older father, is also associated. About 35 percent of clefts have a positive family history.
 
Incidence of Clefting
There are significant ethnic differences in the prevalence of cleft lip and palate, with the highest rates in Asian populations and Native Americans, intermediate rates in Caucasians and lowest rates in African Americans.16-18
  • Clefting in US 1:750 births
  • Asians 2.1:1000 or 1:500
  • Caucasians 1:1000 to 1:75019
    TABLE 1.1   Percentile familial distribution of cleft lip and palate
    Relationship to index case
    Cleft lip/palate
    Cleft palate15
    Siblings (overall risk)
    4.00%
    1.80%
    Siblings (overall risk)
    4.00%
    1.80%
    Siblings (overall risk)
    4.00%
    1.80%
    Siblings (2 affected siblings)
    10.00%
    8.00%
    Siblings and affected parents
    10.00%
    Children
    4.30%
    6.20%
    Second degree relatives
    0.60%
    Third degree relatives
    0.30%
    General population
    0.10%
    0.04%
  • UK 1: 1000
  • Blacks 0.41:1000 or 1:1200
  • Clefts can occur as cleft lip alone, cleft lip/palate, or cleft palate alone (Table 1.1)
  • Cleft lip alone: 21 percent of clefts
  • Cleft lip/palate together: 46 percent of clefts
  • Cleft palate alone: 33 percent of clefts
  • Bilateral cleft lip is associated with a cleft palate in 86 percent of cases
  • Clefts occur more commonly in boys than in girls
Inheritance: Inheritance is variable depending on whether a syndrome is associated and when it is, depending on the syndrome present. It could be autosomal recessive, autosomal dominant, X-linked recessive, X-linked dominant, non-Mendelian inheritance.
 
Classification
Veau classification of clefts of the lip: The severity of cleft lip can range from microform (very small defect) to complete clefts and be unilateral or bilateral. Cleft lip will usually result in minor deformity of the nose characterized by a flattened nostril on the affected side and flaring of the base on the affected side. Cleft lip can involve the alveolus, in which case it has involved the primary palate.
If there is a bilateral cleft of the lip, there may be extension of the premaxillary segment.
Class I—A unilateral notching of the vermilion not extending into the lip
Class II—A unilateral notching of the vermilion border, with the cleft extending into the lip but not including the floor of the nose
Class III—A unilateral clefting of the vermilion border of the lip extending into the floor of the nose
Class IV—Any bilateral clefting of the lip, whether it be incomplete notching or complete clefting.20
Veau classification of clefts of the palate: Cleft palate can occur with cleft lip or less often by itself. Some patients will 8present with submucous clefts where the mucosal lining of the oral cavity roof is present without appropriate supportive bone and muscle structure. Signs of submucous clefting include a bifid uvula, diastasis of soft palate musculature (division of muscles along midline) and notch in hard palate.
Veau divided palatal clefts into four classes as follows:
Class I—Involves only the soft palate.
Class II—Involves the hard and soft palates but not the alveolar process.
Class III—Involves both the hard and soft palates and the alveolar process on one side of the premaxillary area.
Class IV—Involves the soft palate and continues through the alveolus on both sides of the premaxilla, leaving it free and often mobile.21
Kernahan and Stark, 1958 and Spina, 1974, have classified cleft lip and palate depending on embryological principles.
Kernahan and Stark classification21
Group I: Cleft of the primary palate only
  • Unilateral
  • Bilateral
  • Total
  • Subtotal
Group II: Cleft of the secondary palate only
  • Total
  • Subtotal
  • Submucous
Group III: Cleft of the both primary and secondary palate
  • Unilateral—Total, Subtotal
  • Median —Total, Subtotal
  • Bilateral—Total, Subtotal
 
Spina classification21
Group I: Pre-incisive foramen clefts
  • Unilateral
  • Bilateral
  • Median (cleft of the lip with or without an alveolar cleft)—Total, Partial
Group II: Transincisive foramen clefts (cleft of the lip, alveolus and palate)
  • Unilateral
  • Bilateral
Group III: Post-incisive foramen clefts
  • Total
  • Partial
Group IV: Rare facial clefts.
Kernahan, 1971, has proposed stripped Y classification for rapid graphic presentation of the defect. This was subsequently modified by Ehlsaky, 1972 and Millard, 1976.21
The variation in clefts is considerable. A good way to record a cleft lip is by photography. A better way to record a palatal cleft is to fill in the following figure with stripes and dots.
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FIGURE 1.8A: Diagrammatic representation of Kernahan classification for clefts
1, 5: Nasal floor
2, 6: Lip
3, 7: Alveolus
4, 8: Hard palate anterior to incisive foramen
9, 10: Hard palate posterior to incisive foramen
11: Soft palate
12: Congenital velopharyngeal incompetence without obvious clefts
13: Protrusion of premaxilla
In the stripped Y classification, the involved area is shaded by pen to graphically represent the defect (Figs 1.8A and B).
 
Categories of Clefts
Depending on the elemental characteristics of the embryology, anatomy and physiology of the cleft defect, the varieties of clefts of the lip and palate may be tabulated into four general categories:
  1. Those involving the lip and alveolus
  2. Those involving the lip and palate
  3. Those in which the palate alone is affected
  4. Congenital insufficiency of the palate
    The term ‘palate’ will include both the hard palate and the velum or soft palate.
 
Genetic Basis of Nonsyndromic Cleft Lip and/or Palate
Fogh-Anderson, 1942, provided the first population-based evidence that CL +P has a strong genetic component.22
  • Cleft lip and palate syndromes in humans are associated with polymorphisms in the gene (TGF) encoding transforming growth factor-a (TGF), an epidermal growth factor receptor (EGFR) ligand made by most epithelia.9
    zoom view
    FIGURE 1.8B (A to D): Diagrammatic representation of Kernahan classification for clefts
    A: Cleft palate
    B: Left-sided unilateral complete cleft lip and palate
    C: Bilateral complete cleft lip and palate
    D: Bilateral right incomplete, left complete cleft lip and primary palate
  • Extracellular matrix: during the normal merging process, the disappearance of the midline epithelial seam is accompanied by an increase in both proteoglycans (PG) and collagen expression. Control of ECM metabolism in the embryonic oral facial region, therefore, appears to be essential for normal palatal development. ECM molecules in turn promote the activities of growth factors and cytokines present in the epithelial cell and palatal mesenchyme.
  • Although, the role of B-cell leukemia/lymphoma 3 (BCL3) in the etiology of CLP is unknown, proto-oncogene BCL3 is related to genes involved in cell lineage determination and cell cycle regulation.
  • Retinoic acid receptors (RAR): The region on chromosome 11 associated with CLP in this animal model is homologous to 17q21 - q24 in humans.23 This region, marked by retinoic acid receptor a (RAR) has shown association with CLP in some populations.24 This study has strengthened the case for CLP locus linked to RAR in humans.
  • Chromosome 6: Chromosome 6 has been of interest to investigators because of the association of alleles at the H2 locus with corticosteroid induced clefting in the mouse. HLA (on chromosome 6p) is the human homologue of H2.
    zoom view
  • Environmental factors: Naturally occurring folates are found widely in foodstuffs, especially in liver, legumes and fresh vegetables. Folic acid (pteroylmonoglutamic acid) is a commercially available compound used for supplementation. It does not occur naturally in living tissues, but is readily converted in vivo into the biologically active folates. Folates are essential in the synthesis of purines and pyrimidines, which are components of DNA and RNA required in the regulation of gene expression and cell differentiation. In humans, drugs that interfere with folate metabolism, e.g. phenytoin, are known to have teratogenic effects. Low blood folate levels were associated with spontaneous abortion and developmental abnormalities of the fetus.25 However, studies have found significant protective effects of the role of folic acid in orofacial clefting.
  • There also appears to be an association between maternal smoking and oral clefting.26
  • Deficiency of vitamins B1, B2 and B6 in the NMRI strain led to embryolethality, teratogenicity and growth retardation among the fetuses. The cleft palate rate was eight times higher in the deficient group than in the control group.10
TABLE 1.2   Some syndromes associated with cleft lip and/or palate (+ = present, – = absent)
Syndrome
Cleft Lip
Cleft Palate
Stickler syndrome
+
Treacher-Collins
+
van der Woude syndrome
+
+
Pierre Robin syndrome
+
Ectodermal dysplasia syndrome
+
+
Saethre Chotzen syndrome
+
Pallister Hall syndrome
+
Waardenburg syndrome
+
+
Basal cell nevus syndrome
+
+
Pfeiffer syndrome
+
Holoprosencephaly
+
+
Retinoblastoma –
+
Shprintzen Goldberg syndrome
+
Marfan's syndrome
+ (or bifid uvula)
Velocardiofacial
+
DiGeorge syndrome
+
+
Apert syndrome
+
Crouzon craniofacial dysostosis
+
Cleidocranial
+
Langer Giedion syndrome
+
CHARGE syndrome
+
+
 
Genetic Basis of Syndromic Cleft Lip and/or Palate
Syndromic cleft lip and/or palate is seen associated with variety of syndromes which present myriad genetic pictures (Table 1.2). Discussion of the genetic make-up of a few of the common craniofacial syndromes has been dealt with in the chapter on bone pathologies. Both syndromic and nonsyndromic cleft lip and/or palate may be associated with other birth defects that are elaborated in Table 1.3.
 
Prenatal Diagnosis
Ultrasound scanning: For cleft lip, with or without cleft palate, fetal ultrasound studies are the only commonly used test available for prenatal diagnosis (Figs 1.9 and 1.10).
TABLE 1.3   Other birth defects associated with cleft lip and/or cleft palate
System
Specific findings
Facial malformations
• Hypertelorism
• Facial asymmetry
• Hemangiomas
• Choanal atresia
• Microstomia
• Low-set ears
• Auricular malformations
• Preauricular skin tags
• Ear canal atresia
Cardiac system
• Ventricular septal defects
• Transposition of the great vessels
• Patent ductus arteriosus
• Tetralogy of Fallot
• Total anomalous pulmonary venous return
• Single ventricle
• Peripheral pulmonary artery stenosis
Gastrointestinal system
• Pyloric stenosis
• Esophageal atresia
• Anal fistula
• Inguinal hernia
• Diaphragmatic hernia
Central nervous system
• Visual impairment
• Problems with balance
• Hydrocephalus
• Holoprosencephaly
• Seizures
NOTE: These defects can also occur as isolated abnormalities and do not always indicate that the infant has cleft lip and/or cleft palate. A physical assessment must always involve a thorough examination of facial features, including the lip and palate, to rule out cleft lip and/or palate regardless of other findings on examination.
11
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FIGURES 1.9A and B: Cleft lip and palate at 38 weeks showing the two common ultrasound orientations to detect clefting. Left image is axial through the lip and shows a cleft (arrow). Right image is coronal through the tip of the nose, lips and chin. Note the cleft (arrow) which extends into and deforms the nostril (complete cleft lip)
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FIGURE 1.10: Bilateral complete cleft lip/palate (small arrows) with the premaxilla protruding anteriorly as a mass (open arrow)—Axial view through fetal lip at 25 weeks
12
 
CHEILITIS GLANDULARIS
Von Volkman, 1870,37 coined the term cheilitis glandularis and described it as a chronic inflammatory condition of the lower lip characterized by mucopurulent exudates from the ductal orifices of the labial minor salivary glands. It is a chronic progressive and uncommon inflammatory condition of the minor salivary glands.
 
Etiology
  • May be a manifestation of chronic irritation.
  • Factitial trauma, excessive wetting of lips by frequent licking.
  • May be associated with mouth breathing and asthma.
  • Poor oral hygiene
  • Syphilis
  • Heredity
 
Clinical Features
  • Usually found on the lower lip. May also involve upper lip and palate.
  • Cases have been reported in women and children, but occur most often in middle aged men.
  • Eversion of lower lip, inflamed and dilated minor salivary gland ducts, burning sensation at the vermillion border of the lip.
  • Sometimes, a mucopurulent exudate is seen.
  • According to clinical features seen, it is classified into three types:
    1. Simple type: Multiple painless, papular surface lesions with central umbilication.
    2. Superficial suppurative type (Baelz Disease): Painless indurated swelling of the lip with shallow ulceration and crusting.
    3. Deep suppurative (cheilitis glandularis apostematosa): Deep seated infection with formation of abscesses, sinus tracts and fistulas.
 
Histopathologic Findings
  • Lesional tissue shows inflamed, dilated minor salivary gland ducts (Fig. 1.11).
  • In some cases, dysplastic changes may be seen in the overlying surface epithelium.15
zoom view
FIGURE 1.11: Histopathologic picture of cheilitis glandularis showing ductal ectasia, acinar atrophy, interstitial fibrosis and inflammation of minor salivary glands
 
CHEILITIS GRANULOMATOSA
It is a chronic swelling of lip due to granulomatous inflammation.
 
Etiology
Etiology is unknown; a possibility of genetic predisposition has been implicated. Sometimes contact antigens may play a role.
 
Clinical Features
  • The lesion is seen most commonly in young adults.
  • There is no sex predilection.
  • Diffuse or nodular episodic swellings on lip or the face and mostly involving upper lip, lower lip, eyelids and one side of the face (Fig. 1.12).
  • Initially the lesion is soft but as time progress, it becomes rough, dry, painful and firm in consistency; especially those occurring on the lips.
  • Other features include fissured tongue, unilateral or bilateral facial palsy and lymphadenopathy.
 
Histopathologic Features
  • Lesional areas show a central zone of noncaseating granuloma consisting of epitheloid cells and Langhans giant cells (Fig. 1.13).
    zoom view
    FIGURE 1.12: Cheilitis granulomatosa showing diffuse episodic swelling on lower lip
    zoom view
    FIGURE 1.13: Histopathologic picture of cheilitis granulomatosa showing a central zone of non-caseating granuloma
  • Peri and paravascular aggegrates of chronic inflammatory cell infiltrate mostly lymphocytes, plasma cells and histiocytes are seen.
 
PEUTZ-JEGHER'S SYNDROME
Peutz-Jeghers syndrome is an autosomal dominant inherited disorder characterized by intestinal hamartomatous polyps in 16association with mucocutaneous melanocytic macules.32,33 Also called as hereditary intestinal polyposis syndrome, intestinal hamartomatous polyps in association with mucocutaneous melanocytic macules.
A 15-fold elevated relative risk of developing cancer exists in this syndrome over that of the general population; cancer primarily is of the GI tract, including the pancreas and luminal organs and of the female and male reproductive tracts and the lung.
Jeghers, McKusick and Katz (1949) are credited with rediscovery and establishment of clinical significance of generalized intestinal polyposis. First described by Peutz in 1921,34 this obscure syndrome produced melanin spots on oral mucous membranes, extraoral labial tissues and fingers. Jeghers et al presented ten cases in which they described syndromes consisting of same signs and symptoms.35
 
Etiopathogenesis
Goldberg and Goldhaber (1954) believed that inheritance of Peutz-Jeghers syndrome was simple Mendelian dominant and single pleotrophic gene was believed to be responsible for both melanin spots and polyps. Melanin spots and patches varied from 1 to 5 mm.36
The characteristic pathology of Peutz-Jeghers polyps includes extensive smooth muscle arborization throughout the polyp with the appearance of pseudoinvasion because some of the epithelial cells, usually from benign glands, are surrounded by the smooth muscle.
The cause of Peutz-Jeghers syndrome appears to be a germline mutation of the STK11 (serine threonine kinase 11) gene in most cases, located on band 19p13.3.
 
Clinical Features
  • Peutz-Jeghers syndrome has been described in all races.
  • The occurrence of cases in males and females is about equal.
  • The average age at diagnosis is 23 years in men and 26 years in women.
  • Repeated bouts of abdominal pain in patients younger than 25 years are reported.
  • Unexplained intestinal bleeding in a young patient has also been reported.
  • Prolapse of tissue from the rectum may be seen. Rectal mass or rectal polyp is seen.
  • Menstrual irregularities in females (due to hyperestrogenism from sex cord tumors with annular tubules).
  • Precocious puberty may also occur.
  • Cutaneous pigmentation (1 to 5 mm macules) of the perioral region crossing the vermilion border (94 %), perinasal and perioral areas is seen (Fig. 1.14).
    zoom view
    FIGURE 1.14: Peutz-Jegher's syndrome showing cutaneous pigmentation of the perioral region crossing the vermilion border
  • Mucous membrane pigmentation, primarily the buccal mucosa (66 %) is seen.
  • Pigmentation may be present on the fingers and toes, on the dorsal and velar aspects of the hands and feet, and around the anus and genitalia and may fade after puberty.
  • Gynecomastia and growth acceleration (due to Sertoli cell tumor) may be seen.
  • Testicular mass may also be present.
 
Laboratory Findings
A CBC count should be obtained because the polyps may be a source of blood loss.
 
Histopathologic Findings
Characteristic pathology of Peutz-Jeghers polyps includes extensive smooth muscle arborization throughout the polyp, with the appearance of pseudoinvasion because some of the epithelial cells, usually from benign glands, are surrounded by the smooth muscle.
 
LABIAL AND ORAL MELANOTIC MACULE
Oral melanotic macule represents a focal area of melanin deposition, as a result of increase in number of melanocytes, mostly occurring on the buccal mucosa.
Another term labial melanotic macule is used to represent an entity similar to oral melanotic macule, occurring on the vermillion border of the lip (Fig. 1.15).17
zoom view
FIGURE 1.15: Labial melanotic macule presenting as a black, round shaped lesion
 
Clinical Features
  • The lesion may be seen occurring at any age.
  • Incidence of occurrence is more common in females as compared to males.
  • Lesions most commonly occur on lower lip, buccal mucosa, gingiva and palate.
  • It occurs as a dark brown to black, round to oval shaped lesion in the oral cavity.
 
Histopathologic Features
  1. Lesional area shows abundant melanin deposits within keratinocytes in the basal and parabasal layer.
  2. There is no underlying inflammatory cell infiltrate.
 
DEVELOPMENTAL DISTURBANCES OF THE ORAL MUCOSA
  • Fordyce's granules
  • Focal epithelial hyperplasia
 
FORDYCE'S GRANULES
This is not a disease of oral mucosa but a developmental anomaly characterized by heterotropic collection of sebaceous glands at various sites in the oral cavity.
 
Clinical Features
  • Fordyce's granules appear as small yellow spots, either discretely separated or forming relatively large plaques, often projecting slightly above the surface of tissue (Fig. 1.16).
    zoom view
    FIGURE 1.16: Fordyce's granules appearing as small yellow, discretely separated spots
  • They are most frequently found in a bilaterally symmetrical pattern on the buccal mucosa opposite the molar teeth and also on the inner surfaces of lips, in the retromolar region lateral to the anterior faucial pillar and occasionally on tongue, gingiva, frenum and palate.
  • Ectopic sebaceous glands have been discussed in a review by Guiducci and Hyman and may occur in oesophagus, uterine cervix, male genitalia, nipples, palms and soles, parotid gland, larynx and orbit.38
  • Studies by Halperin and coworkers, confirmed by Miles, have indicated that this oral condition is present in approximately 80 percent of the population.39
  • Miles has reported that a large number of sebaceous glands in cheeks and lips may sometimes be found in children long before the age of puberty.40
 
Histopathologic Features
  • In a microscopic view of a Fordyce's granule, sebaceous glands are clearly seen (Fig. 1.17).
  • Sebaceous glands are found normally in large numbers on the skin where they are associated with hair follicles.
  • These sebaceous glands are similar histologically to those seen in skin.
  • A single hair follicle and hair shaft growing from gingiva is a rare occurrence and has been reported by Baughman, 1980.41
  • Glands are superficial and may consist of few or many lobules all grouped around one or more ducts which open on the surface of mucosa.
  • Ducts may show keratin plugging.
 
FOCAL EPITHELIAL HYPERPLASIA
Refer to chapter on epithelial pathology.18
zoom view
FIGURE 1.17: Histopathologic picture of Fordyce's granules showing superficial sebaceous glands consisting of few or many lobules
 
DEVELOPMENTAL DISTURBANCES OF THE GINGIVA
  • Fibromatosis gingivae
  • Retrocuspid papilla
 
FIBROMATOSIS GINGIVAE
Refer to chapter on gingival and periodontal diseases in the pediatric population.
 
RETROCUSPID PAPILLA
It is a small papule that most frequently appears bilaterally on the lingual mucosa of mandibular bicuspid. It was first described by Hirshfeld in 1933.42
 
Clinical Features
  • It occurs as a small, well-circumscribed, soft, pink colored papule, bilaterally on mandibular lingual mucosa between free gingival margin and mucogingival junction.
  • Incidence of occurrence in children and young adults is between 25 to 99 percent and gradually decreases with increase in age.
  • According to Berman and Fay, 1976, the lesion occurs more commonly in males as compared to females.43
 
Histopathologic Features
  • The lesional area reveals vascularized fibrous connective tissue with presence of numerous large stellate fibroblasts containing numerous nuclei.
  • The overlying epithelium is atrophic and may show hyperortho or parakeratosis.
 
DEVELOPMENTAL DISTURBANCES OF THE TONGUE
  • Aglossia and microglossia
  • Macroglossia
  • Ankyloglossia or tongue tie
  • Cleft tongue
  • Fissured tongue
  • Median rhomboid glossitis
  • Benign migratory glossitis
  • Hairy tongue
  • Lingual varices
  • Lingual thyroid nodule.
 
AGLOSSIA AND MICROGLOSSIA
A very rare anomaly, only 35 cases have been reported in a period spanning 258 years. It is mostly associated with cleft palate and dental agenesia.
 
Pathogenesis
Unknown, but may be due to lack of muscular stimulus between alveolar arches, which results in retardation of growth of the mandible in an anterior direction.
 
Clinical Features
  • Microglossia is characterized by an abnormally small tongue.
  • Even though aglossia indicates the absence of a tongue, there is almost always the presence of a rudimentary small tongue.
  • May be associated with oromandibular-limb hypogenesis syndrome. It is characterized by hypodactylia (absence of one or more digits), hypomelia (hypoplasia of part or all of a limb) and microglossia.
  • Microglossia is frequently associated with hypoplasia of the mandible and lower incisors may be missing.
 
MACROGLOSSIA
The term denotes an enlarged tongue. Macroglossia has been described as far back as the era of EgyptianPapyrus Ebers from around 1550 BC (Fig. 1.18).19
zoom view
FIGURE 1.18: Macroglossia
 
Etiology
 
Clinical Features
  • Commonly occurs in children.
  • Ranges from a mild to severe degree.
  • In infants, it may be manifested by noisy breathing, drooling and difficulty in eating
  • Pressure on tongue against the teeth produce crenated lateral borders to the tongue, open bite and mandibular prognathism
  • Tongue may ulcerate, get infected and finally necrosed
  • Macroglossia is associated with Beckwith-Wiedemann syndrome characterized by omphalocele (protrusion of part of the intestine through a defect in the abdominal wall at the umbilicus), visceromegaly, gigantism and neonatal hypoglycemia. It follows an autosomal dominant mode of inheritance and carries a high risk of childhood visceral tumors including Wilms tumor, adrenal carcinoma and hepatoblastoma.
  • Appearance of the tongue varies with the cause:
    • A diffuse, smooth, generalized enlargement is seen in hypothyroidism
    • A multinodular appearance is seen in amyloidosis, neurofibromatosis and multiple endocrine neoplasia
    • A pebbly surface with multiple vesicle like blebs is seen in lymphangioma
    • A papillary surface is seen in Down syndrome
    • Unilateral enlargement is seen in hemifacial hyperplasia.
 
Pseudomacroglossia
  • Pseudomacroglossia is the term applied to a condition which forces the tongue to sit in an abnormal position.
    These conditions could be:
    • Habitual posturing of the tongue
    • Enlarged tonsils or adenoids
    • Low palate
    • Transverse, vertical, anterior/posterior deficiency in the maxillary or mandibular arches
    • Severe mandibular retrognathism, neoplasm displacing the tongue, hypotonia of the tongue 20
 
Histopathologic Features
  • Depends on the specific cause
    • In case of Down syndrome, no histologic abnormality can be detected.
    • In case of a tumor, neoplastic proliferation of a particular tissue may be seen.
    • In case of Beckwith-Wiedemann syndrome, increased muscle tissue is seen.
    • In case of amyloidosis, an abnormal protein material may be seen deposited.
 
ANKYLOGLOSSIA (Fig. 1.19)
It is commonly known as tongue tie. Ankyloglossia occurs when a short lingual frenum attaches to the bottom of the tongue. Mostly occurs in 2 to 3 of every 10,000 people.
 
Clinical Features
  • Occurs as a mild and severe form
  • Mild form is of little clinical significance as compared to the severe form in which the tongue is fused to the floor of the mouth
  • Occurs in 1.7 to 4.4 percent of neonates
  • Follows a male predilection
  • May contribute to the development of an anterior open bite.
  • Clefting of tongue may be occasionally associated with ankyloglossia
  • High mucogingival attachment leads to periodontal problems
    zoom view
    FIGURE 1.19: Tongue-tie due to high lingual frenal attachment
  • Inability to maintain oral hygiene in the mandibular anteriors
  • May result in speech defects
  • May be associated with dyspnea due to upward and forward displacement of the epiglottis and larynx.
 
CLEFT TONGUE
It is a rare anomaly. Mostly occurs due to lack of emergence of lateral lingual swellings. More commonly seen is a partial cleft of the tongue or a manifestation of a cleft as only a deep groove running along the midline of the dorsal surface.
 
Etiology
Incomplete merging and failure of groove obliteration by underlying mesenchymal proliferation.
 
Clinical Features
  • Associated with oral-facial-digital syndrome with thick, fibrous bands in the lower anterior mucobuccal fold eliminating the sulcus and with clefting of the hypoplastic mandibular alveolar process.
  • Food debris and microorganisms may collect at the base of the cleft and cause irritation.
 
FISSURED TONGUE
It is also called as scrotal tongue and lingual plicata. Fissured tongue is a condition frequently seen in the general population that is characterized by grooves that vary in depth and are noted along the dorsal and lateral aspects of the tongue (Fig. 1.20).
 
Etiology
Largely unknown, although Eidelman et al, 1976, suspected a polygenic mode of inheritance because the condition is seen clustering in families who are affected.44
21
zoom view
FIGURE 1.20: Fissured tongue
 
Clinical Features
  • Usually asymptomatic, and the condition is initially noted on routine intraoral examination as an incidental finding.
  • Slight male predilection has been seen.
  • May be diagnosed initially during childhood, but it is diagnosed more frequently in adulthood. The prominence of the condition appears to increase with increasing age.
  • Fissured tongue is also associated with Melkersson-Rosenthal syndrome consisting of a triad of persistent or recurring lip or facial swelling, intermittent seventh (facial) nerve paralysis (Bell palsy) and a fissured tongue.
  • Also associated with Down syndrome and benign migratory glossitis (geographic tongue).
  • Fissured tongue affects the dorsum and often extends to the lateral borders of the tongue. The depth of the fissures varies but has been noted to be up to 6 mm in diameter.
  • When particularly prominent, the fissures or grooves may be interconnected, separating the tongue dorsum into what may appear to be several lobules.
 
Histologic Features
  • A biopsy is rarely performed because of its characteristic diagnostic clinical appearance and little clinical significance.
  • However, histologic examination has shown an increase in the thickness of the lamina propria, loss of filiform papillae of the surface mucosa, hyperplasia of the rete pegs, neutrophilic microabscesses within the epithelium and a mixed inflammatory infiltrate in the lamina propria.45
 
MEDIAN RHOMBOID GLOSSITIS
Median rhomboid glossitis is a condition characterized by a shiny oval or diamond-shaped elevation, invariably situated on the dorsum of the tongue in the midline immediately in front of the circumvallate papillae (Fig. 1.21).46
 
Clinical Features
  • Median rhomboid glossitis presents in the posterior midline of the dorsum of the tongue, just anterior to the V-shaped grouping of the circumvalate papillae.
  • The long axis of the rhomboid or oval area of red depapillation is in the anteroposterior direction.
  • The erythematous clinical appearance is due primarily to the absence of filiform papillae, rather than to local inflammatory changes, as first suggested in 1914 by Brocq and Pautrier.47
  • Most cases are not diagnosed until middle age of the affected patient, but the entity is, of course, present in childhood.
  • 3:1 male predilection is seen.
  • Frequently, irritation occurs by consumption of alcohol, hot drinks or spicy foods.
  • When it occurs in adults, it may be caused due to candidiasis. This has prompted a recent shift towards the more appropriate diagnostic term of posterior midline atrophic candidiasis.
  • Lesions with atrophic candidiasis are usually more erythematous but some respond with excess keratin production and therefore, show a white surface change.
    zoom view
    FIGURE 1.21: Median rhomboid glossitis showing erythematous appearance
    22
  • Infected cases may also demonstrate a midline soft palate erythema in the area of routine contact with the underlying tongue involvement; this is euphemistically referred to as a kissing lesion.
  • Lesions are typically less than 2 cm. in greatest dimension and most demonstrate a smooth, flat surface, although it is not unusual for the surface to be lobulated. Occasional lesions have surface mamillations raised more than 5 mm. above the tongue surface, and occasional lesions are located somewhat anterior to the usual location. None have been reported posterior to the circumvallate papillae.
 
Histopathologic Features
  • Median rhomboid glossitis shows a smooth or nodular surface covered by atrophic stratified squamous epithelium overlying a moderately fibrosed stroma with somewhat dilated capillaries.
  • Fungiform and filiform papillae are not seen, although surface nodules may mimic or perhaps represent anlage of these structures.
  • A mild to moderately intense chronic inflammatory cell infiltrate may be seen within subepithelial and deeper fibrovascular tissues.
  • Chronic candida infection may result in excess surface keratin or extreme elongation of rete processes and premature keratin production with individual cells or as epithelial pearls (dyskeratosis) deep in the processes (Fig. 1.22). Silver staining for fungus will often reveal candida hyphae and spores in the superficial layers of the epithelium. This pseudoepitheliomatous hyperplasia may be quite pronounced and the tangential cutting of such a specimen may result in the artifactual appearance of cut rete processes as unconnected islands of squamous epithelium, leading to a mistaken diagnosis of well differentiated squamous cell carcinoma. Because of this difficulty, it is recommended that the patient be treated with topical antifungals prior to biopsy of a suspected median rhomboid glossitis.
    zoom view
    FIGURE 1.22: Candidal hyphae within the superficial layer of the epithelium
 
BENIGN MIGRATORY GLOSSITIS (GEOGRAPHIC TONGUE)
An inflammatory disease of the tongue characterized by multiple annular areas of desquamation of the filiform papillae, presenting as reddish lesions outlined in yellow that shift from area to area every few days.
 
Etiology
  • It has been reported with increased frequency in patients with psoriasis and in patients with fissured tongue.
  • Although the etiology is unknown, associations with human leukocyte antigen (HLA)-DR5, HLA-DRW6 and HLA-CW6 have been reported.48
 
Clinical Features
  • The lesion shows female predilection, which may be related to hormonal factors.
  • It is more predominant in adults than in children.
  • The tongue exhibits a well-demarcated area of erythema, primarily affecting the dorsum, and often extending to involve the lateral borders of the tongue (Fig. 1.23).
  • Within the area of erythema, the normal tongue architecture is effaced, with loss of the filiform papillae and atrophy of the overlying mucosa.
  • Surrounding this area of erythema is a well-defined, hyperkeratotic, yellow-white border with an irregular serpiginous outline.
 
Histopathologic Features
  • Lesional area shows a lining of keratinized, stratified squamous epithelium with thin and elongated rete ridges.
  • Epithelial area also shows spongiosis and acanthosis. Sometimes, there occurs presence of neutrophils within the epithelium leading to formation of multiple abscesses (Munro abscesses).23
    zoom view
    FIGURE 1.23: Benign migratory glossitis showing depapillation in some areas of tongue
  • Connective tissue shows presence of neutrophils and lymphocytes.
  • Presence of neutrophilic infiltrate may be responsible for destruction of superficial portion of epithelium producing atrophic and reddened mucosa.
 
HAIRY TONGUE
Hairy tongue is a common condition of defective desquamation of the filiform papillae, characterized by marked accumulation of keratin on the filiform papillae of the dorsal tongue. It is also called as lingua nigra, lingua villosa nigra and black hairy tongue. It is uncommonly seen in children.
 
Etiology
Uncertain, but the following associated factors are seen:
  • Antibiotic therapy
  • Poor oral hygiene
  • General debilitation
  • Radiation therapy
  • Use of oxidizing mouthwashes or antacids
  • Overgrowth of fungal or bacterial organisms.
 
Clinical Features
  • Usually appears in the midline, just anterior to the circumvallate papillae, sparing the lateral and anterior borders.
    zoom view
    FIGURE 1.24: Black hairy tongue showing black appearance
  • Papillae may appear brown, black or yellow depending on growth of pigment producing bacteria and staining of food (Fig. 1.24).
  • Tongue appears thick and matted and may occasionally involve the entire dorsal surface.
  • Asymptomatic, but occasionally patients may complain of a gagging sensation due to irritation from the elongated papillae or also of a foul taste in the mouth.
  • Overgrowth of candida albicans may result in glossopyrosis (burning tongue).
  • Clinically and etiologically distinct from hairy leukoplakia.
 
Histopathologic Features
  • Diagnosis is usually clinical and since the lesion is asymptomatic, biopsy is rarely performed.
  • However, on histopathologic examination, marked elongation and hyperparakeratosis of the filiform papillae is seen (Fig. 1.25).
24
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FIGURE 1.25: Histopathologic picture of black hairy tongue showing elongation and hyperparakeratosis of the filiform papillae
 
LINGUAL VARICES
Lingual varices usually involve the lingual ranine veins appearing as red or purple shot like clusters of vessels on the ventral surface and lateral borders of the tongue as well as in the floor of the mouth (A varix is a dilated, tortuous vein, most commonly subjected to increased hydrostatic pressure but poorly supported by surrounding tissue). Usually appear on the ventral surface of the tongue and floor of the mouth, but may also occur on the upper and lower lip, buccal mucosa and buccal commissure. Generally considered an age related disease and rarely seen in the pediatric age group.
 
LINGUAL THYROID NODULE (Fig. 1.26)
Lingual thyroid nodule is nothing but ectopic thyroid tissue usually found between foramen caecum and epiglottis. In fact, 90 percent of all ectopic thyroids are found in this region.
 
Etiopathogenesis
Thyroid gland begins as an epithelial proliferation in the floor of the pharyngeal gut during the 4-5th week of intrauterine life. By the seventh embryonic week, this thyroid bud normally descends into the neck to its final resting position anterior to the trachea and larynx. If the primitive gland does not descend normally, ectopic thyroid tissue may be found between foramen cecum and epiglottis.
 
Clinical Features
  • More frequent in females, probably due to hormonal influences.
  • Symptoms may develop during puberty, adolescence, pregnancy or menopause resulting in large nodular masses which may block the airway, causing dyspnea, dysphagia, dysphonia.
    zoom view
    FIGURE 1.26: Lingual thyroid nodule presenting as a large nodular mass on the posterior surface of the tongue
  • Seventy five percent of patients with infantile hypothyroidism have some ectopic thyroid tissue which may enlarge as a secondary phenomenon, compensating for thyroid hypofunction.
 
Diagnosis
  • Thyroid scan using iodine isotopes or technetium 99 m.
  • Computed tomography and magnetic resonance imaging help in delineating the size and extent of the lesion.
  • Biopsy is avoided due to risk of hemorrhage and also as it may be the patient's only thyroid tissue.
  • Incisional biopsy may be occasionally required in the adult age group, to rule out malignant changes.
 
Histopathologic Features
  • The lesion shows multiple large pieces of thyroid tissue with thyroid follicles of varying size and shape, lined by uniform cuboidal cells and filled with colloid (Fig. 1.27).
  • Some follicles show cystic macrophages in the lumen.
25
zoom view
FIGURE 1.27: Histopathologic picture of a lingual thyroid nodule showing thyroid tissue with thyroid follicles
 
DEVELOPMENTAL DISTURBANCES OF ORAL LYMPHOID TISSUE
  • Reactive lymphoid aggregate
  • Lymphoid hamartoma
  • Angiolymphoid hyperplasia with eosinophilia: This condition is rare in pediatric population and hence does not warrant consideration here.
  • Lymphoepithelial cyst: Refer to the chapter on cysts in children.
 
REACTIVE LYMPHOID AGGREGATE
The lingual tonsil located on the dorsolateral aspect of posterior portion of the tongue frequently becomes inflamed and enlarged. Such an enlargement may be unilateral or bilateral and has been often referred to as ‘foliate papillitis’. Similar reactive hyperplasia may be seen as a firm, nodular, tender mass on the buccal mucosa. Sometimes, lymphoid polyps may be seen on the gingival, buccal mucosa, tongue and floor of the mouth.
 
LYMPHOID HAMARTOMA
It is also called as ‘Castleman tumour'. It is a rare disorder occurring in chest, stomach, neck, armpit, pelvis and pancreas. An abnormal enlargement of lymph nodes in the form of masses is seen in the above locations.
 
Etiology
The cause of Castleman's disease is unknown, but some researchers have implicated the role of increased production of interleukin-6 (IL-6).
 
Types
There are two types of Castleman's disease:
  1. Hyaline-vascular type
  2. Plasma cell type
In hyaline-vascular type, there occur non cancerous growths in lymph nodes and there are no associated symptoms.
Plasma cell type is characterized by fever, weight loss, skin rash, early destruction of red blood cells and hypergammaglobulinemia.
A third form termed as multicentric Castleman's disease has also been described which is characterized by hepatosplenomegaly.
 
DEVELOPMENTAL DISTURBANCES OF THE SALIVARY GLANDS
This section has been discussed in detail in the chapter on salivary gland diseases in children.
  • Aplasia
  • Xerostomia
  • Hyperplasia of palatal glands
  • Atresia
  • Aberrancy
  • Developmental lingual mandibular salivary gland depression
  • Anterior lingual depression.
 
DEVELOPMENTAL DISTURBANCES AFFECTING THE TEETH
They may be further divided as:
 
DEVELOPMENTAL DEFECTS IN SIZE OF TEETH
Tooth size varies among different races and the sexes. The sizes are mostly influenced by hereditary, genetic and environmental factors.
  • Microdontia
  • Macrodontia
 
MICRODONTIA
It is the term implied for unusually small teeth. They are of two types: True and Relative. True form is applied to the teeth that are physically smaller. Sometimes, normal dentition appears small due to presence of large jaws and then the term relative microdontia is applied.
 
Clinical Features
  • It is most commonly associated with hypodontia.
  • It shows a female predilection.
  • Most commonly seen in maxillary lateral teeth, called as ‘peg laterals’. This appears as a reduction in mesiodistal dimension and convergence towards the incisal edges.
  • This condition occurs as an autosomal dominant trait with prevalence in 0.8 to 8.4 percent individuals.
  • Generalized microdontia occurs in Down syndrome and in pituitary dwarfism (Fig. 1.28).26
zoom view
FIGURE 1.28: Generalized microdontia showing interdental spacing
zoom view
FIGURE 1.29: Macrodontia
 
MACRODONTIA (Fig. 1.29)
Opposite of microdontia, it is the term applied to unusual large-sized teeth. They are of two types: True and Relative. True form is applied to the teeth that are physically larger. Sometimes, normal dentition appears large due to crowding or due to presence of smaller jaws and then the term relative macrodontia is applied.
 
Clinical Features
  • It is most often seen associated with hyperdontia.
  • It occurs more commonly in males as compared to females.
  • Diffuse macrodontia is seen in pituitary gigantism and pineal hyperplasia with hyperinsulinalism.
 
DEVELOPMENTAL DEFECTS IN SHAPE OF TEETH
  • Gemination
  • Fusion
  • Concrescence
  • Dilaceration
  • Talon's cusp
  • Dens in dente
  • Dens evaginatus
  • Taurodontism
  • Supernumerary roots
 
GEMINATION (Fig. 1.30)
Initially the term gemination was used for a tooth with a bifid crown and a common root and root canal as a result of a single tooth bud dividing into two. There was a lot of controversy over this definition, as most of the investigators objected over a joining of two teeth in case of maxillary central incisor or joining of maxillary central incisor with a mesiodens to be counted as a single tooth as for then, the tooth number would be correct.
As far as current concepts are concerned, gemination is defined as a single enlarged tooth or joined tooth in which the tooth count is normal, when the anomalous tooth is counted as one.
 
Clinical Features
  • Occurs in both primary and permanent dentitions.
  • Prevalence is 0.5 percent in deciduous teeth and 0.1 percent in permanent dentition.
  • Most commonly seen in maxillary anterior region.
  • Geminated teeth show the presence of a single root canal.
    zoom view
    FIGURE 1.30: Gemination seen in maxillary central incisors
    27
zoom view
FIGURE 1.31: Fusion of left maxillary central and lateral incisors
 
FUSION (Fig. 1.31)
Initially fusion was considered as the union of two normally separated tooth buds with the resultant formation of a joint tooth with confluence of dentin. The current concept defines fusion as a single enlarged tooth or joined tooth in which the tooth count reveals a missing tooth when the anomalous tooth is counted as one.
 
Clinical Features
  • Occurs in both primary and permanent dentitions.
  • Most commonly seen in maxillary anterior region.
  • It is difficult to differentiate between gemination and fusion, but mostly separate root canals are seen in case of fused teeth.
  • Most common occurrence is unilateral, but also occasionally bilaterally seen with the prevalence of 0.02 percent.
 
CONCRESCENCE
Concrescence was defined as the union of two teeth by cementum without confluence of dentin. The same definition holds true in recent concepts.
 
Etiopathogenesis
It may be developmental or inflammatory. Developmental union occurs when two teeth in close proximity fuse at the cementum. Inflammatory union occurs when inflammatory changes at the apical portion of the root of either of the teeth may resolve by fusion of the apices of the two teeth at the cementum.
 
Clinical Features
  • Most commonly seen in the maxillary posterior region.
  • Developmental pattern mostly involves second molar tooth in which its roots are closely placed with the adjacent impacted third molar.
  • Post inflammatory pattern is seen in carious molars in which apices of the roots lie closely to the horizontal or distally angulated third molars.
  • Post inflammatory concrescence must be kept in mind whenever extraction is planned for nonvital teeth with apices that overlie the roots of an adjacent tooth.
 
DILACERATION
Dilaceration is an abnormal angulation or bend in the root or crown of a tooth.
 
Etiopathogenesis
It may arise from an injury that displaces the calcified portion of the tooth germ and remainder of the tooth is formed at an abnormal angle. The bend may also develop due to presence of an adjacent cyst, tumor or odontogenic hamartoma.
 
Clinical Features
  • It occurs most commonly in permanent maxillary incisors followed by mandibular anterior teeth.
  • Deciduous teeth may be involved due to injury during neonatal laryngoscopy and endotracheal intubation.
  • Abnormal angulation may be present anywhere along the length of the tooth (Fig. 1.32).28
    zoom view
    FIGURE 1.32: Dilaceration of the root of maxillary central incisor
  • Age of the patient and the direction and degree of force appear to determine the extent of the tooth's malformation.
  • Affected anterior maxillary teeth fail to erupt in the oral cavity as compared to mandibular anterior teeth.
  • Most of the mandibular anterior teeth erupt in the labial or lingual direction and may be non-vital.
 
TALON'S CUSP (Fig. 1.33)
Talon's cusp is an extra cusp present on the lingual surface of the anterior teeth, extending from the cementoenamel junction to the incisal edge. It appears as a three pronged pattern resembling an Eagle's Talon, hence the name.
 
Clinical Features
  • Incidence of occurrence ranges from 1 to 8 percent.
  • It shows no sex predilection.
  • It may occur unilaterally or bilaterally.
  • Mostly affects permanent maxillary lateral incisors, followed by maxillary central incisors, mandibular incisors and maxillary canines.
  • It is rarely seen in children and mostly occurs on maxillary central incisors.
  • A developmental groove is seen in the area where the cusp fuses with the involved tooth.
    zoom view
    FIGURE 1.33: Talon's cusp in left maxillary central incisor
  • It may be associated with other dental anomalies such as supernumerary teeth, odontomas, impacted teeth, peg shaped lateral incisors, dens invaginatus.
  • Syndromes associated with this anomaly are Rubinstein-Taybi syndrome and Sturge-Weber syndrome.
 
Radiographic Features
On radiographs, the cusp appears overlying the central portion of the crown and includes enamel, dentin and occasionally a pulp horn.
 
DENS IN DENTE
It is also known as dens invaginatus. The term dens in dente is used for the large invagination of dental tissue within a tooth giving a resemblance of a tooth within the tooth.
29
zoom view
FIGURE 1.34: Coronal dens invaginatus seen on left maxillary lateral incisor
zoom view
FIGURE 1.35: Various forms of dens invaginatus
It is an invagination of crown or root, which is lined by enamel. Ohlers described this condition for the first time in 1957.49
 
Types
It is of two types:
  1. Coronal: Invagination of crown portion (Fig. 1.34)
  2. Radicular: Invagination of root portion.
 
Etiopathogenesis
It is hypothesized that before eruption, the lumen of invagination is filled with soft tissue similar to the dental follicle. This soft tissue later on loses its vascular supply and becomes necrotic.
 
Clinical Features
  • Coronal dens invaginatus is most commonly seen with a prevalence of 0.04 to 10 percent.
  • Occurrence is most common in maxillary dentition in decreasing order of lateral incisors, central incisors, premolars, canines and molars.
  • It may be seen as an enlargement of the cingulum pit to a deep infolding extending towards the apex.
  • Coronal dens invaginatus is divided into three types (Fig. 1.35):
    • Type I, where the invagination is seen in the crown.
    • Type II, where the invagination extends below cementoenamel junction that may or may not communicate with the dental pulp.
    • Type III, where the invagination extends through the root and perforates in the apical or lateral radicular area without any communication with the pulp.
  • Sometimes, the invagination may be so dilated that it does not permit the eruption of the tooth, in such cases it is termed as dilated odontome.
  • Radicular dens invaginatus though rare, may be seen to arise secondary to proliferation of the Hertwig's epithelial root sheath. Altered enamel forms an invagination into the dental papilla.
 
Radiographic Features
  • In coronal dens invaginatus, the radiograph shows the invagination into the crown involving enamel, dentin, with or without involvement of pulp with extension only into crown or up to the radicular area (Fig. 1.36).
  • In radicular dens invaginatus, the radiograph shows enlarged roots.
    zoom view
    FIGURE 1.36: Radiographic picture of coronal dens invaginatus affecting the maxillary lateral incisor
    30
zoom view
FIGURE 1.37: Mandibular premolar showing dens evaginatus
zoom view
FIGURE 1.38: Various forms of taurodontism
 
DENS EVAGINATUS (Fig. 1.37)
Dens evaginatus is the exact opposite of dens in dente. It is an elevation of enamel in the central groove or lingual ridge of the buccal cusp of premolar or permanent molar teeth.
 
Clinical Features
  • It is usually bilateral and shows mandibular predominance.
  • The elevation in the form of cusp consists of normal enamel, dentin and pulp.
  • This anomaly is often associated with shovel shaped incisors in which the incisors show prominent lateral margins with hollowing in the center on lingual surface resembling scoop of shovel.
 
TAURODONTISM
(Tauro= bull, dont= tooth). Taurodontism implies an anomaly where there is an enlargement of the body of the pulp chamber with apical displacement of the pulpal floor. It mostly occurs in multi-rooted teeth. It is also called ‘bull tooth’ as it resembles the molar of cud chewing animals.
 
Classification (Fig. 1.38)
It is divided into three types depending upon the degree of apical displacement of the pulpal floor as:
  1. Mild (hypotaurodontism).
  2. Moderate (mesotaurodontism).
  3. Severe (hypertaurodontism).
 
Clinical Features
  • Tooth generally appears rectangular in shape with the pulp chambers showing increased apico-occlusal height with bifurcation close to the apex of the root.
  • The anomaly usually affects permanent teeth and rarely deciduous teeth.
  • It may be unilateral or bilateral.
  • It may occur isolated or may be associated with some syndromes.
  • It has also been reported in association with cleft lip and palate.
 
SYNDROMES ASSOCIATED WITH TAURODONTISM
  • Amelogenesis imperfecta, hypoplastic type, type IE
  • Amelogenesis imperfecta taurodontism, type IV
  • Ectodermal dysplasia
  • Klinefelter syndrome
  • Oral-facial-digital syndrome, type II
  • Down syndrome 31
 
SUPERNUMERARY ROOTS
It refers to the development of an increased number of roots on a tooth compared with that classically described in dental anatomy.
 
Clinical Features
  • Seen in both primary and permanent dentitions.
  • Most commonly seen in third molars due to a developmental malformation. Other teeth affected are molars, mandibular cuspids and premolars.
  • At times, the additional root is small and superimposed over other roots, hence difficult to diagnose.
 
DEVELOPMENTAL DEFECTS IN NUMBER OF TEETH
  • Anodontia
  • Supernumerary teeth
  • Predeciduous dentition
 
ANODONTIA
It is also called as agomphosis, agomphiasis. In dentistry, anodontia, also called anodontia vera, is a rare genetic disorder characterized by the congenital absence of all primary or permanent teeth. Complete anodontia is usually part of a syndrome, usually hereditary hypohydrotic ectodermal dysplasia and seldom occurs as an isolated entity.
Partial anodontia, known as hypodontia or oligodontia, is the congenital absence of one or more teeth, which is relatively common. Congenital absence of all wisdom teeth, or third molars, is relatively common. Hypodontia is genetic in origin and usually involves the absence of 1 to 6 teeth (Fig. 1.39).
zoom view
FIGURE 1.39: Hypodontia showing absence of teeth
Oligodontia is genetic as well and is the term most commonly used to describe conditions in which more than six teeth are missing.
 
Etiology
  • Absence of the entire dental lamina which results in absence of an entire dentition.
  • Absence of one or more tooth follicles resulting in partial anodontia.
  • Absence of tooth follicles of the third molars, mandibular second premolars and maxillary lateral incisors as evolution occurs.
 
Syndromes Associated with Anodontia
  • Cherubism
  • Mulibrey nanism syndrome
  • Gorlin-Chaudhry-Moss syndrome
  • Acro-dermato-ungual-lacrimal tooth syndrome
  • Ectodermal dysplasia (Margarita Island)
  • Rieger syndrome
  • Rothmund-Thomson syndrome
  • Hay-Wells syndrome
  • Schopf-Schulz-Passarge syndrome
  • Rosselli-Gulienetti syndrome
  • Rapp-Hodgkin ectodermal dysplasia syndrome
  • Witkop's syndrome
  • Ellis-van Creveld syndrome
  • Sener syndrome
  • Incontinentia pigmenti
  • Focal dermal hypoplasia 32
    zoom view
    FIGURE 1.40: Schematic representation of classification of supernumerary teeth
  • van der Woude syndrome
  • Ehlers-Danlos syndrome, classic type
  • Focal dermal hypoplasia
  • Hutchinson Gilford syndrome.
 
Clinical Features
  • One or more teeth missing in the dental arch, with no previous history of extraction or exfoliation.
  • Hypodontia has a prevalence of 3.5 to 8 percent (excluding third molars) in the permanent dentition and less than 1 percent in the deciduous dentition (usually involving the mandibular incisors).
  • 20 to 23 percent of the population shows missing third molars.
  • Female predominance of 1.5:1 is seen.
  • After the molars, second premolars and lateral incisors are most frequently absent.
  • Hypodontia is also associated with microdontia, reduced alveolar development, increased freeway space and retained primary teeth.
 
SUPERNUMERARY TEETH
 
Definition
A supernumerary tooth is one that is additional to the normal series and can be found in almost any region of the dental arch.
 
Classification
 
Etiology
  • The etiology of supernumerary teeth is not completely understood.
  • Various theories exist for the different types of supernumerary teeth. One theory suggests that the supernumerary tooth is created as a result of a dichotomy of the tooth bud.50 Another theory is the hyperactivity theory, which suggests that supernumeraries are formed as a result of local, independent, conditioned hyperactivity of the dental lamina.51,52
  • Heredity may also play a role in the occurrence of this anomaly, as supernumeraries are more common in the relatives of affected children than in the general population. However, the anomaly does not follow a simple Mendelian pattern.
 
Clinical Features
  • Brook, 1974, found that supernumerary teeth were present in 0.8 percent of primary dentitions and in 2.1 percent of permanent dentitions.53
  • Occurrence may be single or multiple, unilateral or bilateral, erupted or impacted and in one or both jaws. 33
  • While there is no significant sex distribution in primary supernumerary teeth, males are affected approximately twice as frequently as females in the permanent dentition.
  • In the primary dentition, morphology is usually normal or conical. There is a greater variety of forms presenting in the permanent dentition. However, it is comparatively uncommon in the deciduous dentition.
  • Usually may be asymptomatic and may be discovered on routine radiographic examination.
  • Multiple supernumerary teeth are rare in individuals with no other associated diseases or syndromes.
  • The conditions commonly associated with an increased prevalence of supernumerary teeth include:
    • Cleft lip and palate: Supernumerary teeth associated with cleft lip and palate result from fragmentation of the dental lamina during cleft formation. The frequency of supernumerary permanent teeth in the cleft area in children with unilateral cleft lip or palate or both was found to be 22.2 percent.54
    • Cleidocranial dysplasia: The frequency of supernumeraries in patients with cleidocranial dysplasia ranged from 22 percent in the maxillary incisor region to 5 percent in the molar region.55
    • Gardner syndrome
  • Supernumerary teeth in permanent dentition may be of the following types:
    • Conical: This small peg-shaped conical tooth is the most commonly found supernumerary tooth in the permanent dentition (Fig. 1.41). It develops with root formation ahead of or at an equivalent stage to that of permanent incisors and usually presents as a mesiodens. It may occasionally be found high and inverted into the palate or in a horizontal position. In most cases, however, the long axis of the tooth is normally inclined. The conical supernumerary can result in rotation or displacement of the permanent incisor, but rarely delays eruption.
    • Tuberculate: The tuberculate type of supernumerary possesses more than one cusp or tubercle. It is frequently described as barrel-shaped and may be invaginated. Root formation is delayed compared to that of the permanent incisors. Tuberculate supernumeraries are often paired and are commonly located on the palatal aspect of the central incisors. They rarely erupt and are frequently associated with delayed eruption of the incisors.
    • Supplemental: The supplemental supernumerary refers to a duplication of teeth in the normal series and is found at the end of a tooth series. The most common supplemental tooth is the permanent maxillary lateral incisor, but supplemental premolars and molars also occur. The majority of supernumeraries found in the primary dentition is of the supplemental type and seldom remain impacted.
      zoom view
      FIGURE 1.41: Peg lateral with over-retained deciduous lateral incisor
    • Odontoma: Howard lists odontoma as the fourth category of supernumerary teeth. However, this category is not universally accepted. The term “odontoma” refers to any tumor of odontogenic origin. Most authorities, however, accept the view that the odontoma represents a hamartomatous malformation rather than a neoplasm. The lesion is composed of more than one type of tissue and consequently has been called a composite odontoma. Two separate types have been described: the diffuse mass of dental tissue which is totally disorganized is known as a complex composite odontoma (Fig. 1.42), whereas the malformation which bears some superficial anatomical similarity to a normal tooth is referred to as a compound composite odontoma.
  • Another rare type of supernumerary teeth is a “third set of teeth” that forms underneath and pushes out the second set of teeth, much like the second set formed underneath which pushes out the first set of teeth.
 
Clinical Significance of Supernumerary Teeth
  • Failure of eruption: The presence of a supernumerary tooth is the most common cause of failure of eruption of a maxillary central incisor. It may also cause retention of the primary incisor. The problem is usually noticed with the eruption of the maxillary lateral incisors together with failure of eruption of one or both central incisors. Supernumerary teeth in other locations may also cause failure of eruption of adjacent teeth. 34
    zoom view
    FIGURE 1.42: Odontome in addition to the normal complement of teeth
  • Displacement: The presence of a supernumerary tooth may cause displacement of a permanent tooth. The degree of displacement may vary from a mild rotation to complete displacement. Displacement of the crowns of the incisor teeth is a common feature in the majority of cases associated with delayed eruption.
  • Crowding: Erupted supplemental teeth most often cause crowding. A supplemental lateral incisor may cause crowding in the upper anterior region. The problem may be resolved by extracting the most displaced or deformed tooth.
  • Dentigerous cyst formation may be associated with supernumerary teeth. Primosch, 1981, reported an enlarged follicular sac in 30 percent of cases, but histological evidence of cyst formation was found in only 4 to 9 percent of cases.55 Resorption of roots adjacent to a supernumerary may occur but it is extremely rare.
 
Radiographic Features
  • The buccolingual position of unerupted supernumeraries can be determined using the parallax radiographic principle. The horizontal tube shift method utilizes two periapical radiographs taken with different horizontal tube positions, whereas an occlusal film together with a panorex view is routinely used for vertical parallax. If the supernumerary moves in the same direction as the tube shift it lies in a palatal position, but if it moves in the opposite direction then it lies buccally.
  • Intraoral views may give a misleading impression of the depth of the tooth. A true lateral radiograph of the incisor region assists in locating the supernumeraries that are lying deeply in the palate and enables the practitioner to decide whether a buccal rather than a palatal approach should be used to remove them.
 
PREDECIDUOUS DENTITION
Predeciduous teeth have been described as hornified epithelial structures without roots, occurring on the gingiva over the crest of the ridge, which may be easily removed. They are thought to arise from an accessory bud of the dental lamina ahead of the deciduous bud or from the bud of an accessory dental lamina.
Spouge and Feasby, 1966, believe that predeciduous teeth as an entity is a misinterpretation and such structures present at birth undoubtedly represent only the dental lamina cyst of the newborn.35
zoom view
FIGURE 1.43: Extracted natal tooth
This cyst commonly projects above the crest of the ridge, is white in color and is packed with keratin, so that it appears “hornified” and can be easily removed.57
Natal teeth were first described by Massler, 1950.58 They are also called as accessory teeth which may be present at or shortly after birth (Fig. 1.43).
For the purpose of nomenclature, natal teeth are considered as those teeth present in newborns and neonatal teeth are those which appear in the oral cavity within the first 30 days of life.
However, Neville states that this is an artificial distinction and all teeth should be called as natal teeth.
Spouge and Feasby, 1966, stated that natal teeth rarely represent predeciduous supernumerary teeth; rather most are prematurely erupted deciduous teeth and not supernumerary teeth.
 
Etiology
Several sources suggest a possible hereditary component. The Tlinget Indians in Alaska show a prevalence of 9 percent of their newborns having natal or neonatal teeth, 62 percent of them had affected relatives.59
Environmental factors, especially polychlorinated biphenyls (PCBs) seem to increase the incidence of natal teeth. These children usually show other associated symptoms, such as dystrophic finger nails, hyperpigmentation, etc.
Natal teeth are sometimes associated with various syndromes like Jadassohn-Lewandowsky syndrome, Ellis-van Creveld syndrome, Hallermann-Streiff syndrome, etc.
 
Clinical Features
  • Prevalence of natal teeth is around 1:700 to 1:30,000 depending on the type of study; the highest prevalence being found in the study that relied on personal examination of patients.
    zoom view
    FIGURE 1.44: Natal tooth with Riga Fede disease
  • Kates et al, 1984, stated that 85 percent of the natal teeth are usually mandibular incisors, 11 percent are maxillary incisors and 4 percent are posterior teeth. The vast majority (90-99%) is primary teeth; only 1 to 10 percent are reported to be supernumerary teeth.60
  • Riga Fede disease: Sublingual ulceration may occur in infants as a result of chronic mucosal trauma from adjacent anterior primary teeth, often associated with nursing. These distinctive ulcerations of infancy have been termed Riga Fede disease and should be considered a variation of the traumatic eosinophilic ulceration (Fig. 1.44).
 
Histopathologic Features
Histologically the enamel in natal and neonatal teeth is normal for the age of the child, but when the teeth erupt prematurely the uncalcified enamel matrix wears off because mineralization is not complete. The teeth turn yellow-brown and the enamel continuously breaks down. The usually increased mobility causes histologic changes in the cervical dentin and cementum. Hertwig's sheath may degenerate and root formation may be prevented.
 
DEVELOPMENTAL DEFECTS IN STRUCTURE OF TEETH
  • Amelogenesis imperfecta
  • Environmental enamel hypoplasia
  • Dentinogenesis imperfecta
  • Dentin dysplasia
  • Regional odontodysplasia
  • Dentin hypocalcification
 
AMELOGENESIS IMPERFECTA
Amelogenesis imperfecta (AI) is a diverse collection of inherited diseases that exhibit quantitative or qualitative tooth enamel defects in the absence of systemic manifestations. Also known by varied names such as hereditary enamel dysplasia, hereditary brown enamel, hereditary brown opalescent teeth, this defect is entirely ectodermal, since mesodermal components of the teeth are basically normal. The AI trait can be transmitted by either autosomal dominant, autosomal recessive or X-linked modes of inheritance. Genes implicated in autosomal forms are genes encoding enamel matrix proteins: enamelin and ameloblastin, tuftelin, MMP-20 and kallikrein-4.
Tooth enamel is the most highly mineralized structure in the human body, with 85 percent of its volume occupied by unusually large, highly organized hydroxyapatite crystals.61,62 The physical properties and physiological function of enamel are directly related to the composition, orientation, disposition, and morphology of the mineral components within the tissue.63 During organogenesis, the enamel transitions from a soft and pliable tissue to its final form, almost entirely devoid of protein. The final composition of enamel is a reflection of the unique molecular and cellular activities that take place during its genesis. These activities are controlled by a regulated expression of multiple genes.64 Deviation from this pattern leads to amelogenesis imperfecta. Witkop and Sauk listed the varieties of AI, divided according to whether the abnormality lay in a reduced amount of enamel (hypoplasia), deficient calcification (hypocalcification), or imperfect maturation of the enamel (hypomaturation) and also recognized combined defects (Table 1.4).65
TABLE 1.4   Classification of amelogenesis imperfecta (Witkop and Sauk)
Type I Hypoplastic
IA
Hypoplastic, pitted autosomal dominant
IB
Hypoplastic, local autosomal dominant
IC
Hypoplastic, local autosomal recessive
ID
Hypoplastic, smooth autosomal dominant
IE
Hypoplastic, smooth X-linked dominant
IF
Hypoplastic, rough autosomal dominant
IG
Enamel agenesis, autosomal recessive
Type II Hypomaturation
IIA
Hypomaturation, pigmented autosomal recessive
IIB
Hypomaturation
IIC
Snow capped teeth, X-linked
IID
Autosomal dominant?
Type III Hypocalcification
IIA
Autosomal dominant
IIB
Autosomal recessive
IIB
Autosomal recessive
Type IV Hypomaturation—Hypoplastic with taurodontism
IVA
Hypo maturation–Hypoplastic with taurodontism, autosomal dominant
IVB
Hypoplastic—Hypomaturation with taurodontism, autosomal dominant
Aldred et al, 2003 has given a classification based on:66
  • Mode of inheritance
  • Phenotype—Clinical and Radiographic
  • Molecular defect (when known)
  • Biochemical result (when known)
Amelogenesis imperfecta (AI) is a developmental, often inherited disorder affecting dental enamel. It usually occurs in the absence of systemic features and comprises diverse phenotypic entities.
 
Etiopathogenesis
  • The trait of AI can be transmitted by an autosomal-dominant, autosomal-recessive, or X-linked mode of inheritance.
  • Some of the genes encoding specific enamel proteins have been indicated as candidate genes for amelogenesis imperfecta. Mutational analyses within studied families have supported this hypothesis.37
  • The amelogenin gene is a tooth-specific gene expressed in pre-ameloblasts, ameloblasts and in the epithelial root sheath remnants;67 while a low expression of amelogenin mRNAs has been recently shown in odontoblasts.68,69 To date, there are 14 AMELX-associated AI mutations.70,71
  • The enamelin (ENAM) gene is a tooth-specific gene expressed predominantly by the enamel organ and at a low level, in odontoblasts. The human ENAM gene is localized on chromosome 4 (4q13.3). One autosomal-inherited form of AI, namely, autosomal-dominant amelogenesis imperfecta (ADAI), was linked to a 4Mb region on 4q21. The ENAM gene has been mapped within this locus by radiation hybrid analysis (RHA) and fluorescent in situ hybridization (FISH) and was therefore considered a candidate gene for this type of AI.72,73
  • The ameloblastin (AMBN) gene is expressed at high levels by ameloblasts and at low levels by odontoblasts and pre-odontoblasts, while moderate expression is also observed in Hertwig's epithelial root sheath, and in odontogenic tumors, such as in ameloblastomas.74 The human AMBN is localized on chromosome 4 at locus 4q21 near other genes associated with mineralized tissues: osteopontin, bone sialoprotein and bone morphogenetic protein 3. AMBN maps within the critical region for autosomal-dominant AI and therefore is considered as a candidate gene. However, it was excluded from a causative role by mutational analyses within the families studied by Márdh-Kärrman C et al.75
  • The KLK4 gene is located near the telomere of chromosome 19 (19q13.3–19q13.4) downstream of the KLK2 gene and is considered a member of the human tissue kallikrein gene family.76,77 KLK4 is expressed by both ameloblasts and odontoblasts.
  • Due to abnormal enzymic activity, the crystallites of the enamel grew to the normal length but incompletely in thickness.
  • MMP-20 gene codes for a calcium-dependent proteinase that is a member of the matrix metallopeptidases family (MMPs). Additionally, no other intact, physiologically normal, tissue has been demonstrated to express MMP-20, apart from ameloblasts, pre-ameloblasts and odontoblasts, whereas the expression of MMP-20 in human odontogenic tumors and carcinoma cell lines originating from the tongue has recently been described.78,79
  • The DLX3 gene is a member of the family of homeobox genes that are homologous to the distalless (Dll) gene of Drosophila, known to be expressed during development of the chondrocranium, dermatocranium, sensory organs, brain, limbs and appendages and in the processes of osteogenesis and hematopoiesis.80 Mutation within the human DLX3 gene homeodomain is associated with amelogenesis imperfecta (hypoplastic-hypomaturation type), with taurodontism (AIHHT).
  • However, AMELX, AMBN, ENAM, KLK4 and MMP-20 were excluded from a causative role in two families with autosomal-dominant hypocalcified AI, suggesting that this type of AI is caused by mutation of a gene that is either not known or not considered to be a major contributor to enamel formation.81
  • Mutations in the amelogenin gene (AMELX) cause X-linked amelogenesis imperfecta, while mutations in the enamelin gene (ENAM) cause autosomal-inherited forms of amelogenesis imperfecta. Recent reports involve kallikrein-4 (KLK4), MMP-20 and DLX3 genes in the etiologies of some cases.82
 
Clinical Features
  • The predominant clinical manifestations of affected individuals are enamel hypoplasia (enamel is seemingly correctly mineralized but thin), hypomineralization (subdivided into hypomaturation and hypocalcification), or a combined phenotype, which is seen in most cases.
  • The prevalence of this condition has been estimated to range from 1 in 78 to 1 in 14,000, depending on the population studied. Hypoplastic (AI) represents 60 to 73 percent of all cases, hypomaturation (AI) represents 20 to 40 percent and hypocalcification (AI) represents 7 percent.83
  • The distribution of AI types is known to vary among different populations. In a study in Sweden, 63 percent of the cases were inherited as autosomal-dominant. In contrast, in a study in the Middle East, the most common prevalent type of AI was found to be autosomal-recessive.
 
Radiographic Features
  • The enamel may appear totally absent on the roentgenogram, or when present, may appear as a very thin layer, chiefly over the tips of the cusps and on the interproximal surfaces.
  • In other cases the calcification of enamel may be so affected that it appears to have the same approximate radiodensity as the dentin, making differentiation between the two difficult.
The four major clinical variants have typical clinical and radiographic features.
  1. Hypoplasia: Enamel thickness is reduced such that the dentin shows through and imparts a yellowish-brown color to the tooth. The enamel may be pitted, rough, smooth or glossy. Radiographs demonstrate a square shaped crown, a thin layer of enamel of normal density and low or absent cusps (Figs 1.45 and 1.46).38
    zoom view
    FIGURE 1.45: Clinical appearance of teeth affected by amelogenesis imperfecta
    zoom view
    FIGURE 1.46: Radiographic appearance of teeth affected by amelogenesis imperfecta
    zoom view
    FIGURE 1.47: Ground section of amelogenesis imperfecta showing a reduced enamel thickness and composed of laminations of irregularly arranged enamel prisms
  2. Hypomaturation: The enamel is softer with a normal thickness but mottled appearance. The teeth may appear to be snow - capped. Radiographs reveal enamel whose density is the same as that of dentin.
  3. Hypocalcification: Enamel tends to fracture away shortly after it comes into function. An explorer point under pressure can penetrate the soft enamel. Yet, caries is unusual. Radiographically, enamel thickness appears to be normal but the density is even less as compared to dentin.
  4. Hypomaturation/hypocalcification: The term is referred to depending on the dominant defect. The enamel is usually mottled and discolored. Both the deciduous and permanent dentitions are involved diffusely. In the hypomaturation hypoplastic pattern, the predominant defect is one of enamel hypomaturation in which the enamel appears as mottled yellowish-white to yellow-brown. Pits are seen frequently on the buccal surfaces of the teeth. Radiographically, the enamel appears similar to dentin in density, and large pulp chambers may be seen in single rooted teeth in addition to varying degrees of taurodontism. In the hypoplastic- hypomaturation pattern, the predominant defect is one of enamel hypoplasia in which the enamel is thin; the enamel that is present demonstrates hypomaturation. Except for the decrease in the thickness of enamel, this pattern is similar to the hypomaturation- hypoplastic variant.84
 
Histopathologic Features
  • Histologically, a ground section of teeth involved shows very thin enamel composed of laminations of irregularly arranged enamel prisms (Fig. 1.47).85
  • SEM studies of the extracted deciduous teeth in a case of autosomal recessive rough hypoplastic amelogenesis imperfecta showed the exposed outer enamel surface with irregularly shaped globular protrusions. At the cervical region of the crown, a series of wavy, parallel ridges was seen in the enamel regions. The cementum area was clearly distinguishable from the more coronal region by its mottled and fibrillar pattern and the tendency for the cementum to overlap the ridged coronal structure along the cervical line. Enamel had a high organic content with some abnormal prism formation. The dentinoenamel junction was sharply defined and easily identifiable because of the more homogenous appearance of the enamel matrix, as compared with that of the dentin with its array of collagen fibrils.86
  • The histology of autosomal dominant hypomaturation— hypoplasia type of AI with taurodontism, definitively described by Winter et al, comprises areas of severe hypomineralization with a pore volume of between 1 percent and 25 percent. They described a normal prismatic structure to the enamel, but with considerable post-calcification organic content and occasional bands of globular defects. The dentine was also reported as being defective, with a decreased number of tubules, an increased amount of 39intertubular dentin, dilatations and cellular inclusions. All these findings were more marked in the radicular dentin. The pulp was normal but enlarged in size.87
 
ENVIRONMENTAL ENAMEL HYPOPLASIA
This term implies the defective formation of organic enamel matrix of teeth. It is of two basic types:
  1. Environmental, i.e. influenced by environmental forces.
  2. Hereditary
Ameloblasts in the developing tooth germ are extremely sensitive to external stimuli and many factors can result in abnormalities in enamel.
 
Etiology
The etiological causes may be considered as:
Systemic
  • Birth related trauma: Breech presentations, hypoxia, multiple births, premature birth, prolonged labor
  • Chemicals: Antineoplastic chemotherapy, fluoride, lead, tetracycline, thalidomide, vitamin D
  • Chromosomal abnormalities: Trisomy 21
  • Infections: Chickenpox, cytomegalovirus (CMV), gastrointestinal infections, measles, pneumonia, respiratory infections, rubella, syphilis, tetanus
  • Inherited diseases: Amelo-cerebro-hypohydrotic syndrome, epidermolysis bullosa, mucoploysaccharidosis IV, phenylketonuria, pseudohypoparathyroidism, tuberous sclerosis, vitamin D dependent rickets
  • Malnutrition: Generalized malnutrition, vitamin D deficiency, vitamin A deficiency
  • Metabolic disorders: Cardiac disease, celiac disease, hepatobiliary disease, hypocalcemia, hypothyroidism, hypoparathyroidism, maternal diabetes, toxemia of pregnancy
  • Neurologic disorders: Cerebral palsy, mental retardation, sensorineural hearing defects.
Local
  • Local acute mechanical trauma: falls, neonatal mechanical ventilation, surgery
  • Electric burn
  • Irradiation
  • Local infection: acute neonatal maxillitis, periapical inflammatory disease
    The enamel develops in three major stages:
    1. Matrix formation
    2. Mineralization
    3. Maturation
The timing of the ameloblastic damage has a great impact on the location and appearance of defect in the enamel. The cause of the damage is not particularly important as many local and systemic stimuli can result in defects having similar clinical appearances. The final enamel presents all significant insults received during tooth developments as various defects in it. Deciduous enamel contains a neonatal ring and the rate of enamel apposition is estimated to be 0.023 mm per day. This helps the clinician to accurately time an insult to the deciduous teeth within a week.
 
Clinical Features
  • When examining enamel defects, it is imperative to clean the dentition thoroughly and dry it with gauze. A good source of light from a dental operatory is ideal. Plaque disclosing agents may be used for minor defects.
  • Depending on the extent and stage at which enamel formation has been disrupted, all enamel defects can be clinically classified into one of three patterns:
    • Hypoplasia: Appears as pits, grooves or larger areas of missing enamel.
    • Diffuse opacities: Appear as variations in translucency of enamel. The thickness of enamel is normal, but with increased white opacity which has no clear demarcation from the adjacent normal enamel.
    • Demarcated opacities: Appear as areas of decreased translucence, increased opacity and a sharp boundary 40with the adjacent enamel. The thickness of enamel is normal and the affected opacity may be white, cream, yellow or brown.
  • Environmental enamel abnormalities are extremely common. Small and Murray, 1979, reported that between the ages of 12 to15 years, the prevalence of enamel defects in the permanent dentition was 68.4 percent with 67.2 percent showing opacities, 14.6 percent showing hypoplasia and 13.4 percent showing both hypoplasia and opacities.88
  • Crowns of deciduous teeth start developing from 14th week of gestation till approximately when the child is 12 months of age. Crowns of permanent dentition start developing from 6 months to approximately 15 years of age. The site of coronal damage correlates with the area of ameloblastic activity at the time of injury.
  • Systemic influences like exanthematous fevers that often occur during the first-two years of life commonly present as horizontal rows of pits or diminished enamel on the anterior teeth and first molars.
  • A similar pattern of enamel defects appears on the cuspids, bicuspids and second molars when the event occurs at the age of 4 to 5 years.
  • Another frequent appearance is the Turner's tooth caused due to Turner's hypoplasia of the affected tooth. Turner was the dental clinician who widely publicized the presence of such a pattern of hypoplasia. Turner's hypoplasia can be described as enamel defects seen in the permanent teeth due to disruption of permanent teeth caused by periapical inflammatory disease of the overlying deciduous tooth. Quite a variation of defects occurs as white, yellow or brown discoloration to extensive hypoplasia depending upon the time and severity of the insult. Usually seen in the permanent premolars because of their relationship to overlying deciduous molars.
  • Turner's teeth may also occur due to traumatic injury to deciduous teeth commonly seen in permanent maxillary central incisors. As the permanent incisors develop lingual to the primary teeth, the facial surface of the maxillary incisors is the location frequently affected appearing as a zone of white or yellowish brown discoloration with or without an area of horizontal enamel hypoplasia. Trauma leading to displacement of the already formed hard tooth substance may result in dilaceration and severe trauma early in the development of tooth may result in such disorganization of the bud that the resultant product may result in complex odontoma.
  • Hypoplasia may also arise secondary to the use of therapeutic radiation or chemotherapy provided against childhood cancer, most commonly in patients under the age of twelve, with extensive defects occurring in those under five years of age. Doses as low as 0.72 Gy are associated with mild developmental defects in both enamel and dentin. Apart from dental defects, hypodontia, microdontia mandibular hypoplasia, reduction of the vertical development of the face and reduced alveolar bone growth may occur secondary to radiation.
  • In 1901, Dr Frederick McKay, first reported Colorado brown stains which were later found by HV Churchill in 1930 to have been caused by high concentrations of fluoride (13.7 ppm).89 Dr Trendley H Dean carried out a shoe leather survey in 1931 and recommended the presence of an optimum level of 1ppm F in drinking water to minimize caries, strengthen teeth at the same time avoiding the risk of dental fluorosis.90 Dental fluorosis is the presence of significant enamel defects resulting from ingestion of excessive amounts of fluorides during stages of tooth formation. The appearance of these defects depends upon the level of fluoride in water as well as the time and duration for which the developing tooth was exposed to the excessive levels of fluorides. Dental fluorosis may occur due to excessive levels of fluoride in water, but apart from this a significant ingestion of fluoride may occur from fluoride toothpastes, fluoride supplements, infant formulae, soft drinks, fruit juices and industrial environmental emissions. These may create significant enamel defects through retention of amelogenin proteins in the enamel structure, leading to the formation of hypomineralized enamel. These alterations create a permanent hypomaturation of the enamel in which there is an increased surface and subsurface porosity of the enamel. This enamel structure alters the light reflection and creates the appearance of white, chalky areas. The teeth affected by fluorosis are caries resistant and the altered tooth structure appears as areas of lustureless white opaque enamel that may have zones of yellow to dark brown discoloration. True enamel hypoplasia is uncommon but can occur as deep irregular brownish pits. Clinical diagnosis is usually based on history of excessive fluoride intake.
  • Congenital syphilis results in a distinct pattern of hypoplasia that is extremely rare currently. Anterior teeth are called as Hutchinson's incisors and exhibit crowns that are shaped like straight edged screw-drivers with the greatest circumference present in the middle one-third of the crown and a constricted incisal edge. The middle portion of the incisal edge often demonstrates a central hypoplastic notch. Altered posterior teeth are called as mulberry molars (Moon's molars, Fournier's molars) and demonstrate a constricted occlusal table with a disorganized surface anatomy that resembles the bumpy surface of a mulberry.
  • Syndromes associated with hypoplasia:
    • Down syndrome
    • Tuberous sclerosis 41
    • Epidermolysis bullosa
    • Hurler syndrome
    • Hunter syndrome
    • Treacher Collins syndrome
    • Phenylketonuria
    • Pseudohypoparathyroidism
    • Trichodento-osseous syndrome
    • Vitamin D dependent rickets
    • Lesch-Nyhan syndrome
    • Fanconi's syndrome
    • Sturge-Weber syndrome
    • Turner's syndrome
 
DENTINOGENESIS IMPERFECTA (Fig. 1.48)
Dentinogenesis imperfecta is a hereditary developmental disturbance of dentin in the absence of any systemic disorder. This condition causes the teeth to be discolored (most often a blue-gray or yellow-brown color) and translucent. Teeth are also weaker than normal, making them prone to rapid wear, breakage and loss. These problems can affect both primary teeth and permanent teeth.
 
Classification
Shields, 1973, have described three types of dentinogenesis imperfecta:91
  1. Type I occurs in people who have osteogenesis imperfecta, a genetic condition in which bones are brittle and easily broken.
  2. Dentinogenesis imperfecta type II occurs in people without other inherited disorders and without any association genetically with osteogenesis imperfecta. A few families with type II have progressive hearing loss in addition to dental abnormalities.
  3. Type III was first identified in a population in Brandywine, Maryland. Some researchers believe that dentinogenesis imperfecta type II and type III, along with a similar condition called dentin dysplasia type II, are actually forms of a single disorder.
zoom view
FIGURE 1.48: Clinical picture of dentinogenesis imperfecta showing opalescent dentin
A revised classification mentions only dentinogenesis imperfecta 1 which corresponds to Shields type II and dentinogenesis imperfecta 2 which corresponds to Shields type III.
Another classification was given by Witkop in 1975 that divides dentin defects into three types:92
  1. Dentinogenesis imperfecta
  2. Hereditary opalescent teeth
  3. Brandywine isolate
 
Etiology
  • Mutations in the DSPP gene (gene map locus 4q21.3) cause dentinogenesis imperfecta. They have been identified in people with type II and type III dentinogenesis imperfecta. Mutations in this gene are also responsible for dentin dysplasia type II. Dentinogenesis imperfecta type I occurs as part of osteogenesis imperfecta, which is caused by mutations in one of several other genes.
  • The DSPP gene provides instructions for making proteins like dentin phosphoprotein, dentin sialoprotein and dentin sialophosphoprotein that are essential for normal tooth development. These proteins are involved in the formation of dentin. DSPP mutations alter the proteins made from the gene, leading to the production of abnormally soft dentin. It is unclear how DSPP mutations are related to hearing loss in some families with dentinogenesis imperfecta type II.
  • This condition is inherited in an autosomal dominant pattern. In most cases, an affected person has one parent with the condition.
  • Sauk et al, 1976, found an increase in glycosaminoglycans in EDTA soluble dentin in the teeth from patients of dentinogenesis imperfecta and less glycosaminoglycans in EDTA insoluble residue.93
42
 
Clinical and Radiographic Features
  • Dentinogenesis imperfecta affects an estimated 1 in 6,000 to 8,000 children.
  • The teeth usually involved and more severely affected are deciduous teeth in type 1, whereas in type 2 both the dentitions are equally affected.
  • Common clinical features are bluish-gray teeth, amber-colored teeth, bulbous teeth crowns, absent tooth roots, absent root canals, absent pulp chambers, too small tooth roots, too small root canals, too small pulp chambers, enamel separation from the dentin, malaligned teeth, recurring dental abscess, brittle bones and blue sclera.
  • Dentinogenesis imperfecta 1: Blue-gray or amber brown and opalescent teeth with bulbous crowns. Radiograph reveals narrow roots, small pulp chambers and root canals which may be completely obliterated. Studies of dentin have revealed an increase in as much as 60 percent of water content above the normal level, whereas the inorganic content is less than that of normal dentin. Likewise, the density, X-ray absorption and hardness of dentin are low. Microhardness of dentin is similar to cementum which explains the rapid attrition of the affected teeth.
  • Dentinogenesis imperfecta 2: The crowns of deciduous and permanent teeth wear rapidly after eruption and multiple pulp exposures may occur. The dentin is amber and smooth. Radiographs of deciduous dentition reveal very large pulp chambers and root canals. The permanent teeth have pulpal spaces that are small or completely obliterated. Non-mineralized pulp chambers and canals are seen giving a general appearance of shell teeth (Fig. 1.49).
 
Histopathologic Features
  • Dentinogenesis imperfecta 1: Shows the appearance of normal enamel except for a change in shade which is a manifestation of the dentinal disturbance. Dentin shows irregular tubules with large areas of uncalcified matrix. The tubules are larger in diameter and less numerous than normal dentin. They may be completely absent in few areas. Cellular inclusions probably odontoblasts are also seen and the pulp chamber is usually almost obliterated by the contin ued deposition of the dentin. Odontoblast may degenerate readily and become entrapped in disorganized dentin matrix.
    zoom view
    FIGURE 1.49: Radiographic picture of dentinogenesis imperfecta
  • Dentinogenesis imperfecta 2: Histopathology has not been adequately documented.
 
DENTIN DYSPLASIA
Dentin dysplasia (DD) is a genetic disorder of teeth, characterized by presence of normal enamel but atypical dentin with abnormal pulpal morphology. In 1920 Balchsmiede first reported 8 cases as “root less teeth”.94 Later, Rushton, in 1939, described it as “Dentinal Dysplasia” (DD).95
 
Classification
Carrol et al, published an extensive review of literature and proposed a subclassification based on the radiographic findings. They proposed 2 basic types: Type 1 was classified into 4 subtypes; 1a, 1b, 1c and 1d.96
  • In type 1a, there is a complete obliteration of the pulp and usually little or no root development.
  • The Type 1b variant has a horizontal, crescent shaped, radiolucent line, which separates normal coronal dentin from abnormal radicular dentin. The roots are short, conical and rudimentary.
  • Teeth affected by type 1c variant show 2 crescent-shaped horizontal radiolucent lines with their concavities toward 43each other at the cemento-enamel junction and the roots one half the normal length.
  • Type 1d is characterized by normal root formation, which sometimes may be bulbous in the coronal third. Within the pulp canal “a stone” may be found. In this type of DD, the pulp chamber is usually not obliterated and normal root formation occurs. This is the least severe form of DD. In these cases, the pulp around the stones is healthy. In other cases, the denticle is continuous with dentinal walls.
  • The second type of DD, DD2 is characterized radiographically by extension of the pulp chamber into the root, pulp stones and sudden constriction of the chamber, which forms a thin radiolucent radicular structure.
  • Dean et al97 1997, suggested that an updating of the nomenclature for the developmental disturbances of dentin is indicated, comparable to that presented by Aldred and Crawford, 1995, for developmental disturbances in amelogenesis imperfecta.
 
Etiology
  • The similarity of the primary dentition phenotype between dentinogenesis imperfecta 1 (DGI1) and type II dentin dysplasia suggested that the gene for dentin dysplasia, type II is allelic with the gene for dentinogenesis imperfecta, Shields type II (DGI1), the isolated form of dentinogenesis imperfecta that has been shown by linkage studies to be encoded by a gene on 4q13–q21. Microsatellite markers specific for the area of 4q linked to DGI1 were used. Dean et al, concluded that any candidate gene for DGI1 should also be considered a candidate gene for dentin dysplasia, type II.
  • On the basis of the phenotypic overlap between, and shared chromosomal location with dentinogenesis imperfecta type II, it has been proposed that dentin dysplasia type II and dentinogenesis imperfecta type II are allelic. The substitution in the hydrophobic signal peptide domain caused a failure of translocation of the encoded proteins into the endoplasmic reticulum. The authors hypothesized that this would most likely lead to a loss of function of both dentin sialoprotein and dentin phosphoprotein.
  • Dentin dysplasia usually demonstrates an autosomal dominant inheritance.
  • The abnormal root morphology is postulated secondary to the abnormal differentiation and/or function of the ectomesenchymally derived odontoblasts.
 
Clinical Features
  • Dentin dysplasia type I (radicular type) is characterized by the presence of primary and permanent teeth with normal appearance of the crown but no or only rudimentary root development, incomplete or total obliteration of the pulp chamber and periapical radiolucent areas or cysts. The pulp chamber is sometimes described as having a “crescent shaped” appearance.
    zoom view
    FIGURE 1.50: Clinical features of dentin dysplasia
    zoom view
    FIGURE 1.51: Radiographic picture of dentin dysplasia showing almost complete obliteration of the pulp chamber
  • Dentin dysplasia type II (coronal type) is characterized by primary teeth with complete pulpal obliteration and brown or amber bluish coloration similar to that seen in hereditary opalescent dentin. The permanent teeth have a normal appearance or a slight amber-coloration, the roots are normal in size and shape with a “thistle-tube” shaped pulp chamber with pulp stones (Figs 1.50 and 1.51). In the deciduous dentition, coronal dentin dysplasia bears a resemblance to Dentinogenesis Imperfecta type II.
  • Generally no signs of gingivitis or periodontitis are present. Mobility of teeth may be present due to short, malformed or apparently absent roots.
 
Radiographic Features
Type 1: Roots are short, blunt and conical. In deciduous teeth, pulp chambers and root canals are completely obliterated; in permanent teeth they may be crescent shaped.
Type 2: The pulp chamber of the deciduous teeth become obliterated in deciduous teeth, while in permanent teeth, large 44pulp chamber is seen in coronal portion of the tooth-referred to as “thistle tube” appearance. Pulp stones may also be found.
 
Histopathologic Features
Type I: Normal dentinal tubule formation is blocked and new dentin forms around obstacles. This appearance is typically known as “lava flowing around boulders”.
Type II: In deciduous teeth, the pattern is similar to that in dentinogenesis imperfecta. In permanent teeth, enamel and coronal dentin are normal. Radicular dentin is atubular, amorphous and hypertrophic. Adjacent to the pulp, numerous areas of interglobular dentin are seen. Pulp stones develop in any portion of the chamber.
 
REGIONAL ODONTODYSPLASIA (Fig. 1.52)
Regional odontodysplasia (RO) is a rare, nonhereditary developmental anomaly affecting dental tissues derived from both the mesoderm and ectoderm. The enamel, dentin, and pulp of teeth are affected, and on radiographs the teeth are described as “ghost teeth” (Fig. 1.53).
zoom view
FIGURE 1.52: Clinical picture of regional odontodysplasia showing hypoplastic teeth
zoom view
FIGURE 1.53: Radiographic picture of regional odontodysplasia showing ghost like teeth
The first report of this condition was published by McCall and Wald99 in 1947, but the term ‘odontodysplasia’ was introduced by Zegarelli et al100 in 1963. Since that time, a number of cases have been described under a variety of names; such as localized arrested tooth development, regional odontodysplasia, ghost teeth, odontogenesis imperfecta, unilateral dental malformation, amelogenesis imperfecta non-hereditary segmentalis and familial amelodentinal dysplasia.
 
Etiology
  • Etiology is uncertain but numerous factors have been suggested and considered such as local trauma, irradiation, hypophosphatasia, hypocalcemia, hyperpyrexia. 45
  • Somatic mutation and activation of latent viruses in the odontogenic epithelium have also been linked to the etiology of regional odontodysplasia.
  • Presence of nevus, hemangiomas and hydrocephaly have also been associated with regional odontodysplasia but with no definite evidence.
 
Clinical Features
  • Both the primary and permanent dentitions may be affected in the maxilla, mandible or both together. It appears to have a marked preference for the maxilla.
  • Generally has a higher prevalence in females.
  • Though the condition most often affects only one quadrant, cases with bilateral or multiquadrant involvement have also been reported. The maxillary teeth are affected more frequently than the mandibular, the maxillary central and lateral incisors and canines being more affected than the posterior teeth.
  • In the primary dentition, teeth erupted may be hypoplastic, hypocalcified, with changes in color and form. Affected teeth are likely to be small, brown, grooved and hypoplastic. Gingival tissue can be hyperemic and usually presents a fistula.
  • In the permanent dentition, teeth usually are not erupted or can be partially erupted with fibrous gingival tissue and swelling. Root formation may be immature and roots may be aplastic.
 
Radiographic Features
  • There is a lack of contrast between the enamel and dentin, both of which are less radiopaque than their unaffected counterparts.
  • Additionally, enamel and dentin layers are thin, giving the teeth a ‘ghost-like’ appearance.
  • The pulp chambers are noticeably enlarged with open apices and enlarged follicles.
 
Histopathologic Features
  • Areas of hypocalcified enamel are visible and enamel prisms appear irregular in direction.
  • Coronal dentin is fibrous, consisting of clefts and a reduced number of dentinal tubules; radicular dentin is generally more normal in structure and calcification.
  • Irregular dentin with areas of interglobular dentin and presence of immature odontogenic epithelium in the connective tissue.
  • Pulpal calcification of various degrees is also commonly seen.
  • The mineral content of the affected enamel has been found to be higher than that of dentin in microradiographic studies. The greater density of the enamel is not evident in conventional radiographs, probably because of the thinness of the enamel layer in affected teeth.
 
DENTIN HYPOCALCIFICATION
Normal dentin is calcified by deposition of inorganic material in the form of calcium salts. These calcium salts are deposited in the organic matrix in the form of small globules which fuse with each other. But sometimes these globules do not fuse with each other leaving behind interglobular areas of uncalcified matrix. These areas are visible under the microscope. Dentin hypocalcification is caused by similar factors responsible for environmental enamel hypoplasia, e.g. hypoparathyroidism, rickets, etc. Management of this condition is same as that for dentin dysplasia.
 
DEFECTS OF GROWTH (ERUPTION) OF TEETH
  • Premature eruption
  • Eruption sequestrum
  • Delayed eruption
  • Multiple unerupted teeth
  • Embedded and impacted teeth
  • Ankylosed deciduous teeth
 
PREMATURE ERUPTION
This has already been discussed under the heading of natal teeth.
 
ERUPTION SEQUESTRUM
Eruption sequestrum is a small spicule of calcified tissue that is extruded through the alveolar mucosa that overlies an erupting molar or any other tooth in children. This entity was first described by Starkey and Shafer in 1963.101
 
Etiology
  • As the molar teeth erupt through the bone, they will occasionally separate a small osseous fragment from the 46surrounding contiguous bone, much in the fashion of a corkscrew.
  • In most cases, this fragment probably undergoes total resorption prior to eruption. If the bony spicule is larger or eruption is fast, complete resorption cannot occur and the eruption sequestrum is observed.
 
Clinical Features
  • A small, irregular hard tissue fragment, white in color, with bone-like hardness on the occlusal surface of molars is seen.102 It is seen just prior to or immediately following the emergence of the tips of the cusps through the oral mucosa.
  • The spicule directly overlies the central occlusal fossa but is contained within the soft tissue.
  • Chronic inflammatory alterations may also be observed in the gingiva in the area of contact with the osseous tissue.
  • As the tooth continues to erupt and the cusps emerge, the fragment of bone completely sequestrates through the mucosa and is lost.
  • For a few days, the fragment of bone may be seen lying the crest of the ridge in a tiny depression from which it may easily be removed.
  • The child may complain of a slight soreness in the area, probably produced by compression of the soft tissue over the spicule during eating and just prior to its breaking through the mucosa.
 
Radiographic Features
  • May be diagnosed before eruption of teeth. It appears as a tiny irregular opacity overlying the central occlusal fossa but separated from the tooth itself.
 
Histopathologic Features
  • Histopathologically, the fragments consist of necrosed cortical bone.
  • X-ray microanalyzer findings have revealed the percentages of calcium and phosphorous (by weight) as 78.41 percent and 21.59 percent, respectively, for a calcium to phosphorous ratio of 3.63, which is higher than that seen in normal osseous tissue.
 
DELAYED ERUPTION
Delayed tooth eruption is the emergence of a tooth into the oral cavity at a time that deviates significantly from norms established for different races, ethnicities, and sexes.
 
Etiology
  • Delayed eruption of both deciduous and permanent teeth may be due to systemic or local causes.
  • The following medical conditions are some of the possible systemic causes of delayed eruption of teeth:
    • Hypothyroidism
    • Hypoparathyroidism
    • Cleidocranial dysostosis
    • Gardner syndrome
    • Vitamin D deficiency
    • Ectodermal dysplasia
    • Pyknodysostosis
    • Deficiency of membrane-type 1 matrix metalloproteinase has been found to be associated with delayed eruption and incomplete root formation.103
    • Primary tooth eruption occurs significantly later in children with a birth weight less than 1000 g.104
    • Hauk et al 2001, found a correlation between the progression of HIV infection to pediatric AIDS and delayed dental eruption and this delay is most closely linked to severity of symptoms and not CD4 depletion.105
    • The following local causes are also seen to delay eruption of teeth:
      1. Fibromatosis gingivae
      2. Supernumerary teeth
      3. Retention of deciduous teeth
      4. Crowding of the jaw
  • Since the permanent teeth have a wider range of variation in the time of eruption, it is frequently difficult to pinpoint a retardation of eruption.
47
 
MULTIPLE UNERUPTED TEETH
Multiple unerupted teeth are uncommon without associated local or systemic causes.
 
Etiology
  • Sometimes may be due to a lack of eruptive force, where appearance of teeth and jaws may be normal.
  • May be due to local and systemic causes elaborated in the section on delayed eruption.
 
Clinical Features
  • Multiple retained deciduous teeth with delayed eruption of permanent teeth.
  • Deciduous teeth may have been shed but the permanent teeth may have failed to erupt. This is often called as “pseudoanodontia”.
  • Jaw and appearance of teeth may be normal.
 
Radiographic Features
Jaw and appearance of teeth may be normal.
 
EMBEDDED AND IMPACTED TEETH
Embedded teeth are those teeth that are unerupted due to a lack of eruptive force.
An impacted tooth results from failure of the tooth to erupt into its normal position because of some physical barrier in the path of eruption.
Secondary retention refers to the cessation of eruption of a tooth after emergence neither because of a physical barrier in the path of eruption nor as a result of an unusual position.
 
Etiology
  • Generally this is an acquired condition but it may be genetic.
  • Impaction can be caused by trauma or simply because of the tooth's position in the alveolus so that it is not capable of erupting into its normal position.
  • Lack of space due to crowding of the dental arches may result in partial or complete impaction of a tooth.
  • Loss of space due to premature loss of a primary tooth and subsequent partial closure of the space may also result in impaction.
    zoom view
    FIGURE 1.54: Radiographic picture of an impacted maxillary right central incisor and mandibular left first premolar
  • Not uncommonly, impaction may result due to placement of the tooth in the jaw in a wrong direction. This results in a direction of eruption where the long axis of the tooth is not parallel to a normal eruption path.
 
Clinical Features
  • Impacted and embedded teeth need to be differentiated from missing teeth.
  • It is also important to determine whether a tooth is completely or partially impacted. A completely impacted tooth is one which lies completely within the bone and has no communication with the oral cavity. A partially impacted tooth is not completely encased in bone.
  • Most commonly impacted teeth are maxillary third molars (22 %), followed by mandibular third molars (18 percent) and maxillary canines (0.9 %) (Fig. 1.54).
  • Primary tooth impaction is usually associated with a defect in the development and eruption of the permanent successors.
  • Impaction may be mesioangular, distoangular, vertical, horizontal or inverted; all with buccal or lingual deflection.
  • At times, the mandibular third molar may be situated completely within the ramus of the mandible.
  • Dental caries of an impacted tooth may occur due to a discrete communication of the tooth with the oral cavity.
  • A completely embedded or impacted tooth cannot become carious.
  • Impaction of permanent maxillary cuspids occurs mainly due to:
    • A long eruption pathway from the place of development to that of eruption.
    • Sequence of eruption in the maxillary arch being first premolar followed by canine followed by second premolar. Hence most of the impactions occur simply due to a lack of space.48
  • A maxillary cuspid usually points anteriorly and may impinge on roots of the lateral incisors or premolars.
  • Periodic pain and trismus may also result due to an impacted tooth.
  • A dentigerous cyst may also develop around the coronal portion of an impacted tooth.
  • Impacted teeth allowed to remain in situ may occasionally undergo resorption. However, the cause of resorption is not known.
  • Cases of ameloblastoma have also been reported to form in the wall of such a cyst.
 
ANKYLOSED DECIDUOUS TEETH (Fig. 1.55)
Ankylosis in this context means the fusion of dental hard tissue, cement and dentine with alveolar bone accompanied by loss of soft tissue. In most cases, however, it does not involve the whole periodontal ligament; single bone bridges in the periodontal ligament suffice to disturb the normal vertical development of the tooth in comparison to its unaffected neighbouring teeth. As long as the vertical discrepancy of single or even all deciduous teeth does not exceed 2 to 3 mm, there is no clinical relevance. But if a deciduous tooth reoccludates into bony structure up to the level or even below the gingiva, the successor is always involved. The terms submerged teeth and infraocclusion applied to this condition are inaccurate. Henderson, 1979, pointed that ankylosis should be considered an interruption in the rhythm of eruption.107
zoom view
FIGURE 1.55: Clinical picture of an ankylosed tooth submerged below the occlusal plane
 
Etiology
Etiology of this entity is unknown but three hypotheses have been put forth:
  1. Familial pattern, probably non-sex linked trait.
  2. Intermittent resorption and repair during the routine exfoliation process of the deciduous tooth.
  3. A relationship between congenital absence of permanent teeth and ankylosed primary teeth has been suggested.
 
Clinical Features
  • The lower second deciduous molars are affected most frequently; in the permanent dentition a single or all first molars may show signs of ankylosis. If more permanent teeth of the buccal segment are affected, this is defined as a general disturbance of the periodontal tissue.
  • Ankylosis of primary anterior teeth is a rare phenomenon and occurs following trauma. Alexender et al 1980, reported an unusual case of ankylosis of multiple primary molars where all the primary molars were ankylosed to the alveolar bone.108
  • Usually, ankylosis of the primary molar occurs only after its root resorption begins.
  • If ankylosis occurs early, eruption of adjacent teeth may progress enough that the ankylosed tooth is far below the normal plane of occlusion and may even be partially covered with soft tissue.
  • However, an epithelium lined tract will extend from the oral cavity to the tooth.
  • Ankylosis may occasionally occur even before the eruption and complete root formation of the primary tooth.
  • The ankylosed tooth will have a solid sound when tapped upon with a blunt instrument whereas the normal tooth will have a cushioned sound due to an intact periodontal membrane which absorbs some of the shock of the blow. This test aids in clinical diagnosis of the ankylosed tooth.
 
Radiographic Features
A break in the continuity of the periodontal membrane indicates an area of ankylosis.
 
FISSURAL CYSTS OF THE ORAL REGION
  • Nasopalatine duct cyst
  • Median palatal cyst
  • Globulomaxillary cyst
  • Median mandibular cyst
  • Nasoalveolar cyst
  • Palatal and alveolar cysts of newborns
  • Thyroglossal tract cyst
  • Epidermal inclusion cyst
  • Dermoid cyst
  • Heterotopic oral gastrointestinal cyst
 
NASOPALATINE DUCT CYST
The nasopalatine duct cyst (NPDC) is a developmental, non-neoplastic cyst that is considered to be the most common of the nonodontogenic cysts. NPDC is one of many pathologic processes that may occur within the jawbones, but it is unique in that it develops in only a single location, which is the midline anterior maxilla (Fig. 1.56).
 
Etiopathogenesis
The development of the face and the oral cavity takes place between the fourth and eighth weeks of intrauterine life. The secondary palate is formed during the eighth and twelfth weeks. In the midline between the primary and secondary palates, two channels (the incisive canals) persist. The palatine processes probably partly overgrow the primary palate on either side of the nasal septum. Thus, the incisive canals represent passageways in the hard palate, which extend downward and forward from the nasal cavity. Just before exiting the bony surface of the hard palate (incisive foramen or incisive fossa), the paired incisive canals usually fuse to form a common canal in a Y shape.
zoom view
FIGURE 1.56: Radiographic picture of nasopalatine duct cyst showing radiolucent area in the palate
The fusion of facial processes in the embryologic development of the maxilla results in the formation of a pair of epithelial strands (the nasopalatine ducts) that traverse the incisive canals downward and forward, connecting the nasal and oral cavities. The nasopalatine duct leads from the incisive fossa in the oral cavity to the nasal floor, in which it ends in the nasopalatine infundibulum.
The types of epithelia that line the nasopalatine duct are highly variable, depending on the relative proximity of the nasal and oral cavities. The most superior part of the duct is characterized by a respiratory-type epithelial lining. Moving downward, the lining changes to cuboidal epithelium. In the most inferior portion closest to the oral cavity, squamous epithelium is usually present. In addition to the nasopalatine ducts, branches of the descending palatine and sphenopalatine arteries, the nasopalatine nerve, and mucus-secreting glands are present within the incisive canals.
The nasopalatine ducts ordinarily undergo progressive degeneration; however, the persistence of epithelial remnants may later become the source of epithelia that gives rise to NPDC, from either spontaneous proliferation or proliferation following trauma (e.g. removable dentures), bacterial infection, or mucous retention. Genetic factors have also been suggested. The mucous glands present among the proliferating epithelium can contribute to secondary cyst formation by secreting mucin within the enclosed structure. NPDC can form within the incisive canal, which is located in the palatine bone and behind the alveolar process of the maxillary central incisors, or in the soft tissue of the palate that overlies the foramen, called the cyst of the incisive papilla.
 
Clinical Features
  • Males are affected 1.8 to 20 times more often than females.109
  • NPDCs occur over a wide age range (7to 88 years) and they also occur in fetuses.110 Most patients who are affected are aged 30 to 60 years.
  • Large and more destructive cysts that have perforated the labial and palatal bony plates may present as expansile, fluctuant swellings of the anterior palate and the posterior palate.
  • Extrabony cysts that develop within the soft tissues of the incisive papilla area of the anterior hard palate (called the 50cyst of the incisive papilla) may present as a translucent or bluish colored, dome-shaped swelling. The clinically apparent discoloration is due to accumulation of fluid contents within the cyst.
  • NPDCs clinically demonstrate slow and progressive growth, sometimes exceeding 60 mm in diameter.
  • Tooth displacement is a common finding, having been reported to occur in 78 percent of patients, whereas bony expansion is noted in only 1.4 percent of patients.111
 
MEDIAN PALATAL CYST
Median palatal cyst is an epithelium lined sac containing fluid, present in the midline of the hard palate, between the lateral palatal processes.
 
Etiology
It is of developmental origin.
 
Clinical Features
  • It is asymptomatic and discovered incidentally during routine dental or radiological examination.
  • Its occurrence is rare.
  • A swelling on the oral surface of the hard palate is generally seen.
  • Rarely, it may cause elevation of the nasal floor and nasal obstruction.
 
Radiographic Features
It appears as a radiolucent area in the midline of the palate.
 
Histopathologic Features
  • The cyst consists of a dense fibrous connective tissue lined by stratified squamous epithelium.
  • The connective tissue consists of chronic inflammatory cell infiltrate.
  • Some of the cystic lining shows pseudostratified ciliated columnar epithelium.
 
GLOBULOMAXILLARY CYST
The globulomaxillary cyst is a cyst that appears between a maxillary lateral incisor and the adjacent canine. It was first described by Thoma as a developmental (fissural) cyst.
It is present within the maxilla at the junction of the globular portion of the medial nasal process and the maxillary process.
 
Etiology
It is thought to be a developmental fissural cyst arising in the area between the nasal process and maxillary process. It is now believed that all these lesions are actually other odontogenic cysts, such as odontogenic keratocysts or lateral periodontal cysts. In fact, it is now recommended that this entity should be used only as a clinically descriptive term.
 
Clinical Features
  • Found between the maxillary lateral incisor and the adjacent canine.
  • All regional teeth are found to be vital.
  • It may often cause the roots of adjacent teeth to diverge.
  • This cyst should not be confused with a nasopalatine cyst.
  • The lesion is usually discovered during routine dental examination.
  • It is asymptomatic, but becomes slightly tender if infected.
  • Bilateral lesions are reported, but rarely.
 
Radiographic Features
  • It appears as an oval, round or “inverted pear-shaped radiolucency” on radiographs.
  • According to Wysocki,113 the majority of the lesions (over 80 percent) presenting with the radiographic features of a globulomaxillary cyst are of periapical origin.
 
Histopathologic Features
  • Histologically, it can be a variety of odontogenic lesions predominantly of periapical origin, i.e. periapical cyst and granuloma, odontogenic keratocyst, or more rarely odontogenic myxoma, squamous odontogenic tumor, adenomatoid odontogenic tumor or central giant cell granuloma (the latter is not of tooth origin). However, evidence in literature is in favor of this lesion being predominantly of tooth origin.
  • Histologic features will usually not be supportive of a periapical lesion.51
    zoom view
    FIGURE 1.57: Radiographic picture of median mandibular cyst
 
MEDIAN MANDIBULAR CYST (Fig. 1.57)
It is a soft tissue sac which develops in the mouth near the middle of the lower jaw in conjunction with normal growth or as the result of an odontogenic cyst.
 
Etiology
Two schools of thoughts have been put forth for the origin of this cyst
  1. Some researchers suggest the origin of this cyst from proliferation of epithelial remnants entrapped in the median mandibular fissure during the fusion of mandibular arches.
  2. Cyst may originate from supernumerary enamel organ in the anterior mandibular segment.
 
Clinical Features
  • They are often asymptomatic and diagnosed during routine radiographic examination.
  • They produce expansion of cortical plates.
 
Radiographic Features
It appears either as a unilocular or multilocular well-circumscribed radiolucent lesion.
 
Histopathologic Features
The cyst is lined by stratified squamous epithelium showing numerous papillary projections.
 
NASOALVEOLAR CYST
Nasoalveolar cyst is a fissural cyst arising outside the bones at the junction of the globular portion of the medial nasal process, lateral nasal process, and maxillary process.
 
Etiology
  • It is formed as a result of proliferation of entrapped epithelium along the fusion line of the globular portion of the medial nasal process, lateral nasal process, and maxillary process.
  • Roed-Peterson,114 1969, and Christ,115 1970, suggested that the cyst originates from the lower anterior part of the naso-lacrimal duct, rather than the entrapment of epithelium.
 
Clinical Features
  • Most commonly seen in females.
  • Incidence of occurrence ranges from 12 to 75 years of age.
  • Causes a swelling in the mucolabial fold and floor of the nose.
 
Histopathologic Features
The cyst is lined by pseudostratified or stratified ciliated columnar epithelium containing goblet cells (Fig. 1.58).
The following have been discussed in the section on cysts in the pediatric population:
  • Palatal and alveolar cysts of newborns
  • Thyroglossal tract cyst
  • Epidermal inclusion cyst
  • Dermoid cyst
    zoom view
    FIGURE 1.58: Histopathologic picture of nasoalveolar cyst showing stratified ciliated columnar epithelium containing goblet cells
    52
Heterotopic oral gastrointestinal cyst is generally not seen in the pediatric population, hence does not warrant explanation in this textbook.
REFERENCES
  1. Lannelongue V, Menard M. Affections congenitales, 1891 vol 1 Hasselin and Houzeau,  Paris:  423.
  1. Robin P. La chute de la base de la langue considérée comme une nouvelle cause de gans la respiration naso-pharyngienne. Bull Acad natl Med (Paris), 1923:89:37–41.
  1. Taylor WB, Lane DJ. Congenital fistulas of the lower lip. Arch Dermatol, 1966:94:421.
  1. McConell FMS, Zellweger H, Lawrence RA. Labial pits: cleft lip and/or palate syndrome. Arch Otolaryngol, 1970:91:407.
  1. Neville BW, Damm DD, Allen CM, Bouquot JE. Chpter 1: Developmental defects of the oral and maxillofacial region. In: Oral and Maxillofacial Pathology, Saunders,  2nd edition, 2005:45.
  1. Van der Woude A. “Fistula labii inferioris congenita and its association with cleft lip and palate”. Am J Hum Genet, 1954:6(2):244–56.
  1. Helms JA, et al. Sonic hedgehog participates in craniofacial morphogenesis and is down-regulated by teratogenic doses of retinoic acid. Dev Biol 1997:187:25–35.
  1. Kerrigan JJ, Mansell JP, Sengupta A, Brown N, Sandy JR. Palatogenesis and potential mechanisms for clefting. JR Coll Surg Edinb, 45, December 2000:351–8.
  1. Ferguson MWJ. Developmental mechanisms in normal and abnormal palate formation with particular reference to the etiology, pathogenesis and prevention of cleft palate. Br J Orthod 1981:8:115–37.
  1. Ferguson MWJ. Palate development. Development 1988:103:41–60.
  1. Shapiro BL, Sweney L. Electron microscopic and histochemical examination of oral epithelial-mesenchymal interaction (programmed cell death). J Dent Res 1969:48:652–60.
  1. Gartner LP, Hiatt JL, Provenza DV. Palatal shelf epithelium: A morphologic and histochemical study in X-irradiated and normal mice. Histochem J 1978:10:45–52.
  1. Fitchett JE, Hay ED. Medial edge epithelium transforms to mesenchyme after embryonic palatal shelves fuse. Develop Biol 1989:131:455–74.
  1. Sun D, Vanderburg CR, Odierna GS, Hay ED. TGFb3 promotes transformation of chicken palate medial edge epithelium to mesenchyme in vitro. Development 1998a;125:95–105.
  1. Marazita ML, Spence MA, Melnick M. Major gene determination of liability to cleft lip with or without cleft palate: a multiracial view. J Craniofac Genet Dev Biol 1986:2(Suppl): 89–97.
  1. Melnick M, Marazita ML, Hu DN. Genetic analysis of cleft lip with or without cleft palate in Chinese kindreds. American J Med Genet; 1986:21:183–90.
  1. Murray JC. Gene/environment causes of cleft lip and / or palate. Clinical Genet; 2002:61:248–56.
  1. Bonaiti-Pellie C, et al. An epidemiological and genetic study of facial clefting in France. I. Epidemiological and frequency in relatives. J Med Genet 1982:11:374–7.
  1. Ralph E McDonald, David R Avery. Dentistry for the child and adolescent; seventh edition; Harcourt India Pvt Ltd;  2001;742–4.
  1. Tandon S, Kumar P. Chapter 11: Dental care for the special child. In Tandon Shobha's Textbook of Pedodontics, Paras Publishing:  2003:576–9.
  1. Murray C Jeffrey. Face facts: Genes, environment and clefts. Am J Hum Genet 1995:57:227–32.
  1. Jurilof DM, Mah DG. The major locus for multifactorial nonsyndromic cleft lip maps to mouse chromosome 11. Mamm Genome 1995:6:63–9.
  1. Chenevix-Trench G, Jones K, Green AC, Duffy DL, Martin NG. Cleft lip with or without cleft palate: associations with transforming growth factor alpha and retinoic acid receptor loci. Am J Hum Genet 1992:51:1377–85.
  1. Hartridge T, Illing HM, Sandy JR. The role of folic acid in orofacial clefting. Brit J Orthod 1999:26:115–20.
  1. Kallen K. Maternal smoking and orofacial cleft. Cleft Palate Craniofac J 1997:34:11–6.
  1. Watson ACH, Sel DA, Grunwell P. Management of cleft lip and palate. Whurr Publishers,  London and Philadelphia  2005:117–9
  1. Bradbury E, Bannister P. Chapter 8: prenatal, perinatal and postnatal counseling. Whurr Publishers,  London and Philadelphia  2005:119–20.
  1. Bradbury E, Bannister P. Chapter 8: prenatal, perinatal and postnatal counseling.
  1. Policy on management of patients with cleft lip/palate and other craniofacial anomalies. American Academy of Pediatric Dentistry: Reference Manual 2004–2005;26:7;154–5.
  1. Damle SG. Chapter 48: Dental management of patients with cleft lip and cleft palate. In Pediatric Dentistry. Arya Medi Publishing House 2001:293–5.
  1. Neville BW, Damm DD, Allen CM, Bouquot JE. Abnormalities of the teeth. In: Neville BW, Damm DD, Allen CM, Bouquot JE, (Eds): Oral and Maxillofacial Pathology. 1st ed. WB Saunders;  Philadelphia, Pa:  1995:653–4.
  1. Rajendran R, Shivapathasundharam B. Developmental disturbances of Oral and Paraoral structures. In: Shafer's textbook of Oral Pathology. Elsevier,  5th edition, 2006:29–30.
  1. Peutz JLA. Very remarkable case of familial polyposis of mucous membrane of intestinal tract and nasopharynx accompanied by peculiar pigmentations of skin and mucous membrane. Nederl Maandischr v Geneesk 1921:10:134–46.
  1. Jeghers H, Mc Kusick FA, Katz KH. Generalized intestinal polyposis and melanin spots of oral mucosa, lips and digits: a syndrome of diagnostic significance. New England J Med, 1949:241-25:993–1005.
  1. Goldberg, Hyman, Goldhaber Paul. Hereditary intestinal polyposis with oral pigmentation. Oral Surg, Oral Med, Oral Pathol, 1954:7:378–82.

  1. 53 Von Volkmann R, Einige Falle von Cheilitis Glandularis, Apostematosa (Myxadenitis Labialis). Virchows Arch Pathol Anat 1870:50:142–4.
  1. Guiducci A, Hyman AB. Ectopic sebaceous glands. Dermatologica, 1962:125:44.
  1. Halperin V, Kolas S, Jefferis KR, Huddleston SD, Robinson HBG. The occurence of Fordyce spots, benign migratory glossitis and fissured tongue in 2,478 dental patients. Oral Surgery, 1953:6:1072.
  1. Miles AEW. Sebaceous glands in the lip and cheek mucosa of man. Br Dent J, 1958:105:235.
  1. Baughman RA, Heidrich Jr. PD, The oral hair: an extremely rare phenomenon. Oral Surg 1980:49:530.
  1. Hirshfeld I. The retrocuspid papilla. Am J Orthod, 1947:33:447.
  1. Berman FR, Fay JT. The retrocuspid papilla. A clinical survey. Oral Surg, 1976:42:80.
  1. Eidelman E, Chosack A, Cohen T. Scrotal tongue and geographic tongue: polygenic and associated traits. Oral Surg Oral Med Oral Pathol 1976:42(5):591–6.
  1. Rogers RS. Melkersson-Rosenthal syndrome and orofacial granulomatosis. Dermatol Clin 1996:14(2):371–9.
  1. James William D, Berger Timothy G, et al. Andrews’ Diseases of the Skin: Clinical Dermatology. Saunders Elsevier,  2006.
  1. Brocq L, Pautrier LM. Glossite losangue mediane de la face dorsale de la langue. Ann Derm Syph (Paris) 1914:5:1–18.
  1. Gonzaga HF, Torres EA, Alchorne MM, Gerbase-Delima M. Both psoriasis and benign migratory glossitis are associated with HLA-Cw6. Br J Dermatol Sep 1996:135(3):368–70.
  1. Oehlers FA. Dens invaginatus: Variation of the invagination process and associated posterior crown forms. Oral Surg 1957:10:1302–16.
  1. Liu JF. Characteristics of premaxillary supernumerary teeth: a survey of 112 cases. ASDC J Dent Child 1995:62:262–5.
  1. Levine N. The clinical management of supernumerary teeth. J Can Dent Assoc 1961:28:297–303.
  1. Brook AH. Dental anomalies of number, form and size: their prevalence in British schoolchildren. J Int Assoc Dent Child 1974:5:37–53.
  1. Vichi M, Franchi L. Abnormalities of the maxillary incisors in children with cleft lip and palate. ADSC J Dent Child 1995:62:412–7.
  1. Jensen BL, Kreiborg S. Development of the dentition in cleidocranial dysplasia. J Oral Pathol Med 1990:19:89–93.
  1. Primosch RE. Anterior supernumerary teeth - assessment and surgical intervention in children. Pediatr Dent 1981:3:204–15.
  1. Di Biase DD. The effects of variations in tooth morphology and position on eruption. Dent Pract Dent Rec 1971:22:95–108.
  1. Spouge JD, Feasby WH. Erupted teeth in the newborn. Oral Surg 1966:22:198.
  1. Massler M, Savara BS. Natal and Neonatal teeth. J Pediatr 1950:36:349.
  1. Mayhall JT. Natal and neonatal teeth among the Tlinget Indians. J Dent Res 1967:46:748–9.
  1. Kates GA, Needleman HL, Holmes LB. Natal and neonatal teeth: a clinical study. J Am Dent Assoc 1984:109:441–3.
  1. Robinson C, Briggs HD, Atkinson PJ, Weatherell JA. Matrix and mineral changes in developing enamel. J Dent Res 1979:58:871–82.
  1. Simmer JP, Fincham AG. Molecular mechanisms of dental enamel formation. Crit Rev Oral Biol Med 1995:6:84–108.
  1. Mahoney EK, Rohanizadeh R, Smail FSM, Kilpatrick NM, Swain MV. Mechanical properties and microstructure of hypomineralized enamel of permanent teeth. Biomaterials 2003:25:5091–100.
  1. Paine ML, White SN, Luo W, Fong H, Sarikaya M, Snead ML. Regulated expression dictates enamel structure and tooth function (review). Matrix Biol 2001:20:273–92.
  1. Witkop CJJ. Amelogenesis imperfecta, dentinogenesis imperfecta and dentin dysplasia revisited, problems in classification. J Oral Pathol 1989:17:547–53.
  1. Aldred MJ, Savarirayan R, Crawford PJM. Amelogenesis imperfecta: A classification and catalogue for the 21st century. Oral Disease 2003:9:19–23.
  1. Cook DC. Hereditary enamel hypoplasia in a prehistoric Indian child. J Dent Res 1980:59:1522.
  1. Schulze C. Beitrag zur Frage der “angeborenen Schmelzhypoplasie.” Dtsche Zahn Mund Kieferheilkd 1952;16:108–36.
  1. Schulze C. Erbbedingte Strukturanomalien menschlicher Zahne. Urban and Schwarzenburg,  Miinchen:  1956.
  1. Winter GB, Brook AH. Enamel hypoplasia and anomalies of the enamel. Dent Clin North Am 1975:19:3–24.
  1. Haug RH, Ferguson FS. X-linked recessive hypomaturation amelogenesis imperfecta: report of a case. J Am Dent Assoc 1981:102:865–7.
  1. Witkop CJ, Stewart RE. Amelogenesis imperfecta. In: Stewart RE, Barber TK, Troutman KC, Wei SHY (Eds). Pediatric dentistry: scientifc foundations and clinical practice. CV Mosby;  St Louis:  1982. p. 110.
  1. Witkop CJ. Genetic disease of the oral cavity. In: Tiecke RJ, (Ed): Oral Pathology, McGraw-Hill,  New York:  1965:805.
  1. Escobar VH, Goldblatt LI, Bixler D. A clinical, genetic, and ultrastructural study of snow-capped teeth: X-linked amelogenesis imperfecta, hypomaturation type. Oral Surg Oral Med Oral Pathol 1981:52:607–14.
  1. Crawford PJ, Aldred MJ. X-linked amelogenesis imperfecta. Presentation of two kindreds and a review of the literature. Oral Surg Oral Med Oral Pathol 1992:73:449–55.
  1. Schulze C. Erbbedingte Strukturanomalien menschlicher Zahne. Acta Genet Med Gemellol 1957:7:231–5.
  1. Witkop CJ, Sauk JJ. Heritable defects of enamel. In: Stewart RE, Prescott GH (Eds). Oral facial genetics. CV Mosby;  St Louis:  1976. p. 151–226.
  1. Sauk JJ, Lyon HW, Witkop CJ. Electron optic microanalysis of two gene products in enamel of females heterozygous for X-linked hypomaturation amelogenesis imperfecta. Am J Hum Genet 1972:24:267–76.

  1. 54 Darling AI. Some observations on amelogenesis imperfecta and calcifcation of the dental enamel. Proc R Sot Med 1956:49:759–65.
  1. Backman B, Anneroth G. Microradiographic study of amelogenesis imperfecta. Scand J Dent Res 1989:97:316–29.
  1. Backman B, Anneroth G, Horstedt P. Amelogenesis imperfecta- a scanning electron microscopic and microradiographic study. J Oral Pathol Med 1989:18:140–5.
  1. McLarty EL, Giansanti JS, Hibbard ED. X-linked hypomaturation type of amelogenesis imperfecta exhibiting lionization in females. Oral Surg Oral Med Oral Pathol 1973:36:678–85.
  1. Witkop CJ. Hereditary defects in enamel and dentin. Acta Genet Med Gemollol (Roma) 1957:7:236–9.
  1. Schulze C. Developmental abnormalities of teeth and jaws. In: Gorlin RJ, Goldman HM (Eds). Thoma's oral pathology. 6th ed. CV Mosby;  St Louis:  1970. p. 130–6.
  1. Ooya K, Nalbandian J, Noikura T. Autosomal recessive rough hypoplastic amelogenesis imperfecta. A case report with clinical, light microscopic, radiographic and electron microscopic observations. Oral Surg Oral Med Oral Pathol 1988:65:449–58.
  1. Backman B, Holmgren G. Amelogenesis imperfecta: a genetic study. Hum Hered 1988:38:189–206.
  1. Aldred MJ, Crawford PJ. Amelogenesis imperfecta-towards a new classifcation. Oral Dis 1995:1:2–5.
  1. Murray JJ, Shaw L. Classification and prevalence of enamel opacities in the human deciduous and permanent dentitions. Arch Oral Biol 1979:24:7–13.
  1. Churchill HV. Occurrence of fluorides in some water of the United States. Ind Eng Chem 1931:23:996–8.
  1. Dean HT. Classification of mottled enamel diagnosis. J Am Dent Assoc 1934:21:1421–6.
  1. Shields ED, Bixter D, El-Kafrawy AM. Proposal classification for heritable human dentin defects with a description of new entity. Arch Oral Biol 1973:18:543–53.
  1. Witkop Jr. CJ, Hereditary defects of dentin. Dent Clin N Am, 1975:19:25–45.
  1. Sauk JJ Jr, Witkop Jr, CJ Brown DM, Corbin KW Glycosaminoglycans of EDTA soluble and insoluble dentin in dentinogenesis imperfecta type I. Oral Surg Oral Med Oral Pathol 1976:41(6):753–7.
  1. Balchsmiede G. Disseration In Steidler NE, Radden BG, Reade PC. Dentinal dysplasia; a clinicopathological study of eight cases and review of literature: Br JOral Maxillofac Surg 1984:22:274–86.
  1. Rushton MA. A case of dentinal dysplasia: Guys Hosp. Rep. 1939:89:369–73.
  1. Carrol MKO, Duncan WK, Perkins TM. Dentin dysplasia: Review of literature and a proposed sub classification based on radiographic findings. Oral Surg 1991:72:119–25.
  1. Dean JA, Hartsfield Jr, JK Wright JT, Hart TC. Dentin dysplasia, type II linkage to chromosome 4q J Craniofac Genet Dev Biol 1997;17:172–7.
  1. Munoz-Guerra MF, Naval-Gias L, Escorial V, Sastre-Perez J. Dentin dysplasia type I treated with onlay bone grafting, sinus augmentation, and osseointegrated implants. Implant Dent, 2006:15(3):248–53.
  1. McCall JO, Wald SS. Clinical dental roentgenology. 3rd ed. WB Saunders;  Philadelphia:  1952. p. 170.
  1. Zegarelli EV, Kutscher AH, Applebaum E, Archard HO. Odontodysplasia. Oral Surg Oral Med Oral Pathol 1963:16:187–93.
  1. Starkey PE, Shafer WG. Eruption sequestra in children. J Dent Child 1963:30:84.
  1. Maki K, Ansai T, Nishida I, Zhang M, Kojima Y, Takehara T, Kimura M. Eruption sequestrum: x-ray microanalysis and microscopic findings. J Clin Pediatr Dent 2005:29(3):245–7.
  1. Bartlett JD, Zhou Z, Skobe Z, Dobeck JM, Tryggvason K. Delayed tooth eruption in membrane type-1 matrix metalloproteinase deficient mice. Connect Tissue Res 2003:44 (Suppl 1):300–4.
  1. Viscardi RM, Romberg E, Abrams RG. Delayed primary tooth eruption in premature infants: relationship to neonatal factors. Pediatr-Dent 1994:16(1):23–8.
  1. Hauk MJ, Moss ME, Weinberg GA, Berkowitz RJ. Delayed tooth eruption: association with severity of HIV infection. Pediatr Dent 2001:23(3):260–2.
  1. Hua F, Zhang L, Chen Z. Trigger osteoclast formation and activation: molecular treatment strategy of delayed tooth eruption. Med Hypotheses 2007:69(6):1222–4.
  1. Henderson HZ. Ankylosis of primary molars: a clinical, radiographic and histologic study. J Dent Child, 1979:46:117–22.
  1. Alexender SA and others: Multiple ankylosed teeth. J Pedod 1980:4:354–9.
  1. Cabrini RL, Barros RE, Albano H. Cysts of the jaws: a statistical analysis. J Oral Surg 1970:28(7):485–9.
  1. Abrams AM, Howell FV, Bullock WK. Nasopalatine cysts. Oral Surg Oral Med Oral Pathol 1963:16:306–32.
  1. Swanson KS, Kaugars GE, Gunsolley JC. Nasopalatine duct cyst: an analysis of 334 cases. J Oral Maxillofac Surg 1991:49(3):268–71.
  1. Bodin I, Isacsson G, Julin P. Cysts of the nasopalatine duct. Int J Oral Maxillofac Surg 1986:15(6):696–706.
  1. Wysocki GP. The differential diagnosis of globulomaxillary radiolucencies. Oral Surg 1981:51:281.
  1. Roed-Peterson B. NAsolabial cysts: a presentation of five patients with a review of literature. Br J Oral Surg 1969:7:84.
  1. Christ TF. The globulomaxillary cyst: an embryologic misconception. Oral Surg 1970:30:515.