Developmental anomalies of the oral cavity: the relationship between oral health and genetic disorders, part II. (Developmental Anomalies).

It is estimated that about 25% of Mendelian disorders have craniofacial manifestations. The great majority of chromosomal disorders and several environmental disorders affect the oral cavity, in this paper we will describe isolated, as well as associated, oral anomalies and/or traits.

ISOLATED ORAL ANOMALIES

Anomalies of Tooth Number

Missing Teeth This trait is known as hypodontia, the congenital absence of one or more teeth. The term anodontia should be reserved for the total absence of primary and secondary teeth, and modifications of anodontia (i.e., partial anodontia, pseudoanodontia) should not be used at all.

Hypodontia is a rather common characteristic of contemporary men; the incidence ranges from 2% to 6%, excluding third molars, and higher incidences have occasionally been reported. The incidence varies among populations. Family studies have shown absence of the upper lateral incisor is controlled by one autosomal dominant gene with high transmittal occurance and variable expression. It may occur unilaterally or bilaterally, and nine combinations of peg-shaped, absent, and normal incisors have been described.

Absence of the third molar is common and is thought to be controlled by polygenes. It has been reported as both autosomal dominant and autosomal recessive. Although the trait has been known for more than a century, no conclusive data are available. Certain patterns of missing teeth have lately been described as single gene disorders.

Supernumerary Teeth The presence of supernumerary teeth is known as hyperdontia, which is observed less frequently than hypodontis. In most cases, supernumerary teeth are not visible; roentgenograms are necessary to document the presence of impacted supernumerary teeth. Supernumerary teeth vary in morphology. Although they may have characteristics similar to normal teeth, a great number of them are abnormally shaped. Supernumerary teeth are common in the maxillary anterior area (mesiodens) and the maxillary molar area (distomolars or fourth molars). Some cases of supernumerary teeth have been shown to be compatible with genetic transmission.

Anomalies of Tooth Structure

Two main categories of defects affecting enamel and dentin have been described: defects caused by environmental factors during the development of teeth and defects caused by genetic factors.

Environmental Defects

Tetracycline Stain Drugs such as tetracycline are well known as agents that produce discoloration of the teeth. Generally, the color ranges from yellow to slightly brown or blue. The teeth affected are those that were mineralizing while the drug was used. Tetracycline is incorporated with calcium and may be observed in dentin or enamel, which are tooth structures. A clinical history of treatment with tetracycline and fluorescent teeth (yellow fluorescence) under ultraviolet light are criteria in making the diagnosis.

Fluorosis Fluoride ingested with drinking water may produce fluorosis, changes in the enamel. Fluorosis ranges from a few white flecks to brown stains. When fluorosis is severe, the surfaces of teeth appear eroded. The brown color results from hypoplastic enamel and is observed mainly in areas where the fluoride concentration in drinking water is higher than 2 ppm.

Vitamin Deficiencies Nutritional deficiencies may also account for structural defects of teeth. Vitamin D deficiency causes rickets and dental changes that may be manifested as large pulp chambers with high pulp horns, enamel hypoplasia, and microexposures of pulp horns that result in abscesses. In vitamin A deficiency, although enamel hypoplasia is not seen clinically, there is histological alteration of enamel and dentin. Enamel hypoplasia has also been reported in vitamin D hypervitaminosis.

Trauma Trauma during tooth development may cause severe enamel hypoplasia or dilaceration of the teeth. Intrusion of the primary teeth into developing permanent teeth is a common cause of such defects.

Virus Infections in early pregnancy caused by viruses such as rubella may produce dental defects such as hypodontia and enamel hypoplasia of the primary teeth. However, the evidence is not conclusive.

Inherited Enamel Defects (amelogenesis imperfecta)

This group of well-established disorders has been divided into three main types: hypoplastic, hypocalcified, and hypomature. The criteria for classification are the clinical, roentgenographic, and histological features of the enamel.

Hypoplastic Amelogenesis Imperfecta Several types of hypoplastic amelogenesis imperfecta have been described. The enamel may be smooth, pitted, rough or locally rough (all autosomal dominant), or it may have alternating vertical bands of normal and abnormal enamel (X-linked dominant). Lack of interproximal contact because of lack of normal depth of the enamel layer is frequently observed in the smooth and rough types of hypoplastic amelogenesis imperfecta. The enamel may vary from yellowish to brownish, and generally both primary and permanent teeth are affected.

Hypocalcified Amelogenesis Imperfecta This is the most common type of amelogenesis imperfecta. The enamel may be stained by exogenous agents and tends to be brown or black. In hypocalcified amelogenesis imperfecta, the enamel surface is pitted and chips off, thereby exposing the dentin. The teeth are sensitive to changes in temperature. Roentgenographically, the enamel is of normal thickness but has a moth-eaten appearance. The mode of inheritance is autosomal dominant.

Hypomature Amelogenesis Imperfecta Several types of hypomature amelogenesis imperfecta have been described. Generally, discoloration of the enamel ranges from white to yellow-brown. A dental explorer may penetrate the surface of the enamel in the X-linked recessive type. In the autosomal recessive type, the enamel tends to chip away. Enamel cannot be distinguished from dentin on the roentgenogram.

Inherited Dentin Defects

Dentinogenesis Imperfecta Synonyms such as hereditary opalescent dentin have been used to describe opalescent brown teeth as a heritable, isolated defect. Dentinogenesis imperfecta is manifested as discoloration (brown to blue) of teeth that wear down easily just through chewing. The crowns of teeth, especially the bicuspids and molars, are bulbous in appearance, with a constriction at the junction of enamel and cementum. Roentgenographically, the bulbous appearance and constriction at the cervix are more evident, and obliteration of pulp chambers and the root canals can be seen. The roots have also been described as short. The roentgenographic findings mentioned are typical of dentinogenesis imperfecta and of opalescent dentin-enamel teeth associated with osteogenesis imperfecta.

In dentinogenesis imperfecta, the enamel chips off easily, apparently because of a lack of physical retention at the dentin-enamel junction. The exposed dentin is susceptible to attrition. In some cases the crowns of the teeth are worn away and opalescent brown roots with obliterated root canals are observed.

Preventive treatment should include steel crowns on primary molars to avoid attrition and loss of vertical dimension. In permanent teeth, full dentures over crowned teeth have been shown to be successful. Full crowns over teeth with dentinogenesis imperfecta have not been fully accepted because of fear of fractures at the level of the pronounced constriction, but cases have been reported in which such treatment is successful.

Dentin Dysplasia Other dentin anomalies include dentin dysplasia with its variants. Type I is recognized roentgenographically as agenesis of the roots, while pulp obliteration in primary teeth, thistle-tube pulp and numerous pulp stones in permanent teeth are characteristic of type II. Both defects are inherited as autosomal dominant traits, and teeth in both dentitions are affected.

Anomalies Of Bone

Torus Palatinus A hard bony structure generally located in the posterior midline of the hard palate is known as torus palatinus. This bony exostosis is a benign tumor that may show a domelike form or may be lobulated. Occasionally it is present as a spindle running anteroposteriorly at the midline of the palate. Generally it is observed in adults and adolescents, but personal observations have been made at earlier stages. Torus palatinus should be surgically removed in patients with speech impairment and when the patient is a candidate for upper dentures.

Torus Mandibularis An exostosis on the lingual surface of the mandible, generally near the site of the canines, is known as torus mandibularis. This exostosis may be single or multiple, is usually bilateral and, like the toms palatinus, is a benign tumor. Surgical excision is the treatment of choice if the torus interferes with speech or dentures. Torus mandibularis has been reported to be autosomal dominant.

ORAL ANOMALIES ASSOCIATED WITH GENETIC DISORDERS

An increasing number of oral anomalies of the hard and soft tissues are being recognized as associated with multiple-system disorders. In several cases, the oral findings represent manifestations of the syndrome: in other cases, the oral findings are coincidental. Several syndromes are described below in which the oral findings are a recognized manifestation of the syndrome.

Anomalies of Tooth Number Associated with Genetic Syndromes

Congenitally missing teeth and supernumerary teeth have been shown to be associated with several inherited syndromes. Congenitally missing teeth are seen in Witkop syndrome, Book syndrome, hypohidrotic ectodermal dysplasia, incontinentia pigmenti, Ellis-van Creveld syndrome, Hallermann-Streiff syndrome, focal dermal hypoplasia, lipoid proteinosis, Rieger syndrome, otodental dysplasia, Coffin-Lowry syndrome, trichodental syndrome and others. Supernumerary teeth have been documented in cleiodocranial dysplasia and Gardner syndrome. A few of these will be discussed as examples of the nature of abnormal numbers of teeth in syndromes.

Hypohidrotic Ectodermal Dysplasia, X-Linked Recessive This is the most common type of ectodermal dysplasia; males are severely affected while females are carriers and very mildly affected. The disorder is characterized by sparse thin hair, multiple congenitally missing teeth, abnormal conically shaped teeth, lack of sweat pores and nail abnormalities. In these patients, both dentitions are affected; teeth, when present, are abnormal in shape and smaller in size. On occasion, patients may be completely edentulous. In regions where teeth are missing the alveolar ridges are poorly developed or even flat.

Dental treatment may require construction of dentures that are well tolerated, even for children at four years, of age. Dental implants are an excellent alternative for older children and there are now several centers that utilize this procedure. A good resource of information is the National Foundation for Ectodermal Dysplasia (http://www.nfed.org).

Witkop Syndrome or Tooth and Nail Syndrome This syndrome is characterized by multiple congenitally missing teeth, conical deciduous and permanent teeth and dysplastic nails. At birth, nails are very small or nonexistent. Later, they may remain smaller than normal; some, particularly the thumbnail and the nail of the big toe, may have a flat or depressed center with the appearance of a spoon-shaped nail.

This condition will not affect the sweat pores or the hair, and it is an autosomal dominant trait. Because this condition is relatively benign, people are treated only for the correction of their teeth and little attention is given to the nail abnormalities.

Incontinentia Pigmenti This disorder is a genodermatosis characterized by a pigmentary change of the skin resulting in hyper-pigmented tattooing of the skin. In addition, people with the disorder may show a variety of malformations of the hair, eyes, teeth, skeleton, and central nervous system. They may also have developmental delays. Dystrophy of the nails occurs infrequently and is usually mild. Possible teeth abnormalities include congenitally missing teeth, conically shaped teeth, and small teeth (microdontia). Skin changes may disappear with age, and mothers of children with incontinentia pigmenti should be examined for orodental findings that may be the only clinical evidence that they have the disorder.

Incontinentia pigmenti is inherited as an X-linked dominant disorder and in males is usually lethal prenatally. A good source of information is the Incontinentia Pigmenti International Foundation at http://imgen.bcm.tmc.edu/IPIF.

Coffin-Lowry Syndrome This syndrome includes mental retardation, faciodigital anomalies, skeletal abnormalities and orodental abnormalities. The facies is characterized by progressive coarsening of the facial features, along with hypertelorism, antimongoloid slanting of the palpebral fissures, prominent supraorbital ridges, short and anteverted nares, open mouth (in males), pouty lower lip, thick bulging chin, and protuberant ears. It may be confused with that seen in the mucopolysaccharidoses, Williams syndrome, Down syndrome, or acromegaly in adolescents. Skeletal findings include marked scoliosis, pectus excavatum, hyperextensible hands and flat feet. The hands are pudgy, with distally tapering fingers. Orodental findings in Coffin-Lowry syndrome include malocclusion, midline furrow of the tongue and hypodontia. The syndrome is thought to be X-linked or sex-influenced autosomal dominant.

Rieger Syndrome Rieger syndrome is the autosomal dominant association of goniodysgenesis (abnormal development of the anterior chamber of the eye), congenitally missing teeth, and failure of involution of the periumbilical skin (prominent belly button). Goniodysgenesis in Rieger syndrome is manifested primarily as a prominent Schwalbe line, hypoplasia of the iris stroma, and iridocorneal synechiae. Glaucoma, cataract, and microcornea may be associated with the goniodysgenesis. The upper anterior teeth are those absent most frequently. The mandibular incisors are often conical in shape or absent and one or more of the premolars may be absent.

Cleidocranial Dysplasia Cleidocranial dysplasia is characterized by lack of normal development or absence of the clavicle bone, late ossification of cranial sutures, frontal and parietal bossing, shortness of stature and orodental abnormalities. The syndrome is autosomal dominant, Delayed eruption of teeth or lack of teeth have been described; the teeth are actually impacted, and their presence is revealed by radiographs. Supernumerary teeth are one of the most peculiar characteristics of the syndrome. Their shape is similar to that of bicuspids.

Tooth Morphology Alterations Associated with Genetic Syndromes

Otodental Dysplasia Otodental dysplasia plasia is an ectodermal dysplasia characterized by sensorineural deafness and large, bulbous teeth. The age of onset and progression of deafness vary. Some affected individuals may even reach middle adult life without a hearing impairment.

The crowns of molars in affected individuals are larger than average, bulbous, and lack normal cusp and sulcus occlusal patterns. The premolars are frequently smaller than average or absent altogether. In some families only the deciduous canines are affected, while in others both the deciduous and permanent canines are involved, becoming large and bulbous. Pulp stones may be seen on radiographs of affected teeth. The pulp chambers appear to be duplicated, and taurodontism (long pulp chambers and short roots) may be present. Otodental dysplasia is inherited as an autosomal dominant trait with high transmittal occurence and variable expression of the associated defects.

Morquio Syndrome This syndrome is also called mucopolysaccharidosis IV. Its manifestations are platyspondylisis, corneal opacities, keratosulfate excretion in urine and characteristic dental abnormalities. The skeletal changes include progressive spinal deformity, short neck, pectus carinatum, and marked growth failure. In a study of 12 patients with the condition, the anterior teeth were noted to be widely spaced and flared. The posterior teeth were tapered and had pointed cusp tips. The enamel was normal in hardness, but some had pitted surfaces. The hard palate was broad and flat, and dental radiographs showed hypoplastic enamel. The dental findings are unique among genetic mucopolysaccharidoses and are a good adjunct for clinical diagnosis. The syndrome is autosomal recessive.

Ellis-van Creveld Syndrome This syndrome shows hypodontia and alteration of crown morphology. The morphology of the remaining teeth, especially the anterior teeth, is characterized by conically-shaped lateral incisors or cuspids and barrel-shaped central incisors. The lateral margins of lingual surfaces of these teeth appear enlarged, and a high and prominent cingulum is common. Other dental findings include neonatal teeth, serrated alveolar ridge, supernumerary frenula and pseudo cleft lip resulting from a hyperplastic midline frenum.

Taurodontism In taurodontism the pulp chambers are enlarged in an apical direction and the bifurcation or trifurcation point of the molars is also displaced toward the apex. As a result, the tooth has the shape of a block with small divergent roots. Because the crown is not affected, taurodontism is essentially a radiographic finding. There are several syndromes associated with this unusual trait; this clinical sign may be helpful in the characterization of a given disorder. Syndromes with taurodontism include:

* Klinefelter syndrome, or 47 XXY, and also in individuals with an extra X chromosome such as XXXY or in those with XY:XXYY mosaicism;

* Trichodento-osseous syndrome;

* Mohr syndrome, or orofaciadigital syndrome type II;

* Hajdu-Cheney syndrome;

* Taurodontism, microdontia, dens invaginatus;

* Stoy syndrome (taurodontism, hypodontia, sparse hair);

* Ackerman syndrome (taurodontism, pyramidal and fused molar roots, juvenile glaucoma, unusual morphology of the upper lip).

Anomalies of Tooth Structure Associated with Genetic Syndromes

Trichodento-Osseous Syndrome The trichodento-osseous syndrome is potentially another ectodermal dysplasia, but the reported increase in bone density may remove it from the strict definition of ectodermal dysplasia. It is an autosomal dominant syndrome of excessively curly hair, enamel dysplasia, and radiodense bones. Affected individuals have tightly curled hair at birth; the hair may remain curly throughout life or may become straighter with age. The teeth are affected by enamel dysplasia that has been reported to involve hypoplasia, hypocalcification and, less commonly, hypomaturation. Other dental findings include increased dental caries and delayed dental eruption. Individual teeth can be affected by more than one type of dysplasia, most commonly a combination of hypoplasia and hypocalcification. Taurodontism is present in the trichodento-osseus syndrome, as is a higher-than-expected occurrence of impacted teeth. The cortices of bones appear excessively dense but normal in thickness on roentgenograms. Some affected individuals may have brittle nails that split longitudinally, but no other defects are consistently associated with the syndrome.

Osteogenesis Imperfecta This disease is characterized by bone fragility, blue scleras, hearing abnormalities and dental abnormalities. These last are clinically similar to those observed in dentinogenesis imperfecta: opalescent teeth with bulbous crowns and obliterated pulp chambers and root canals. A history of bone fragility and hearing impairment helps to differentiate dentinogenesis imperfecta from osteogenesis imperfecta.

A classification of osteogenesis imperfecta has been proposed on the basis of the dental findings associated with osteogenesis imperfecta tarda. This classification includes at least two autosomal dominant types, one in which the teeth are opalescent and one in which the teeth are normal. Because opalescent teeth may be evident at the eruption of first lower central incisors at approximately 6 months of age, the dental signs often precede bone fractures in cases of so-called osteogenesis imperfecta tarda.

Pseudohypoparathyroidism There are two types of pseudohypoparathyroidism; they show similar enamel defects. Both are X-linked traits. The enamel defects vary according to sex, the stage of tooth development, and onset of the biochemical changes associated with pseudohypoparathyroidism. In females the enamel of teeth is markedly pitted. In males the enamel is hypoplastic and thin. The roots of affected teeth are generally more tapered than normal, and the apex remains open longer than usual. The disorder results from an abnormal response to parathyroid hormone; although the hormone is normal in amount, both hypocalcemia and hyperphosphatemia occur.

Anomalies of the Jaw Associated with Genetic Syndromes

Pyknodysostosis This syndrome is characterized by small stature, bone abnormalities, persistence of the fontanelles, large head with occipital prominence, prominent nose, short fingers caused by hypoplasia of the distal phalanges, and absence of the angle of the mandible. Absence of the angle of the mandible is a constant feature that is virtually pathognomonic. Other dental abnormalities include premature eruption of the teeth and hypodontia. Pyknodysostosis is inherited as an autosomal recessive trait.

Cherubism Cherubism is characterized by symmetric bilateral enlargement of the mandible. The condition may begin as early as 2 years of age. The lesion is hard to the touch, and painless. In some instances, cherubism may affect the maxilla, with involvement of the floor of the orbit. This complication displaces the globe upward and exposes the scleral rims, suggesting a cherubic look. A summary of a report on a 4-year-old male of apparently triracial extraction can be illustrative. There was no history of consanguinity or of a similar condition in his family. The child, who was referred to us with a diagnosis of Noonan syndrome, was short in stature and had a congenital heart defect, bilateral palpebral ptosis, and bilateral enlargement of the mandible in the area of the first and second molars. Roentgenograms revealed characteristic multiloculated radiolucencies in the area of the molars that extended almost to the lower border of the mandible. Several teeth were displaced by lesions.

The natural history of cherubism shows that the lesions of the maxilla and mandible eventually regress. The regression may be noticed during puberty, yet later in life no sequelae of the condition are found. The man described above was monitored into adulthood. Although he has virtually no facial deformation now, he has very poor dentition because of caries and tooth displacement because of bone deformation. Furthermore, the alveolar ridge has a decreased height. In this particular case we found lesions on the ribs that were radiologically and cytologically similar to the lesions of the mandible. Cherubism is autosomal dominant, and many cases display new mutations.

Gardner Syndrome Gardner syndrome is characterized by a triad of alterations that include multiple osteomas, soft tissue lesions such as epidermoid cysts and fibromas of the skin, and multiple polyposis of the large intestines. The most common sites for osteomas in this syndrome are the frontal bone, maxilla, mandibular angle, and lower border of the mandible. Other orodental findings include multiple odontomas, supernumerary teeth, and impacted teeth.

Recognition of the osteomas is important because they generally precede the appearance of intestinal polyposis, which has a marked tendency towards malignant degeneration. By 30 years of age about 50% of cases are of malignant degeneration, and the percentage increases with age. Potential colon cancer may warrant prophylactic colon removal in early adult life.

SUMMARY

In this article and Part I (December 2001 issue), we have illustrated the relationship between oral-dental findings and genetic disorders. Some oro-dental findings, such as congenitally missing teeth, amelogenesis imperfecta or cleft of the lip and palate, may be isolated defects. However, there is ample evidence of oral-dental findings that are found as part of a more complex systemic disorder. The clinical relevance of the findings varies; they may only be descriptive, such as a fissured tongue in Down syndrome, but in other cases missing teeth may represent an important finding in the diagnosis of ectodermal dysplasia, X-linked recessive, incontinentia pigmenti or Rieger syndrome. Brownish or opalescent baby teeth may be the first sign of osteogenesis imperfecta, while freckle-like spots on the lips may indicate intestinal polyposis, as in Peutz Jeghers syndrome.

We would like to emphasize that children with special health care needs should be examined by a dentist by the time they are one year old. This will allow the dentist to advise the parents about nutritional aspects, oral hygiene habits, and preventive measures. Furthermore, the dentist will play an important role in the integral approach regarding health care needs of the child, in collaboration with the physician and the parents. Good dental health goes far beyond having good teeth. Let us work together to bring a bright smile to our special children!

Dr. Carlos F. Salinas is Professor and Director of the Division of Craniofacial Genetics, Department of Pediatric Dentistry and Orthodontics, College of Dental Medicine at the Medical University of South Carolina, Charleston, SC.