Developmental Disturbances of Oral and Paraoral Structures
Craniofacial anomalies (CFA) are a diverse group of deformities in the growth of the head and facial bones. Anomaly is a medical term meaning ‘irregularity’ or ‘different from normal’. These abnormalities are congenital (present at birth) and have numerous variations: some are mild, others are severe and require surgery.
• Combination of genes. A child may receive a particular combination of gene(s) from one or both parents, or there may be a change in the genes at the time of conception, which results in a craniofacial anomaly.
• Folic acid deficiency. Folic acid is a B vitamin found in orange juice, fortified breakfast cereals, enriched grain products, and green, leafy vegetables. Studies have shown that women who do not take sufficient folic acid during pregnancy, or have a diet lacking in folic acid, may have a higher risk of having a baby with certain congenital anomalies, including cleft lip and/or cleft palate.
Cleft lip. An abnormality in which the lip does not completely form. The degree of the cleft lip can vary greatly, from mild (notching of the lip) to severe (large opening from the lip up through the nose).
Cleft palate. Occurs when the roof of the mouth does not completely close, leaving an opening that can extend into the nasal cavity. The cleft may involve either side of the palate. It can extend from the front of the mouth (hard palate) to the throat (soft palate). The cleft may also include the lip.
• Craniosynostosis. A condition in which the sutures in the skull of an infant close too early, causing problems with normal brain and skull growth. Premature closure of the sutures may also cause the pressure inside the head to increase and the skull or facial bones to change from a normal, symmetrical appearance.
• Hemifacial microsomia. A condition in which the tissues on one side of the face are underdeveloped, affecting primarily the ear (aural), mouth (oral), and jaw (mandibular) areas. Sometimes, both sides of the face can be affected and may involve the skull as well as the face. Hemifacial microsomia is also known as Goldenhar syndrome, brachial arch syndrome, facio-auriculovertebral syndrome (FAV), oculo-auriculovertebral spectrum (OAV), or lateral facial dysplasia.
• Vascular malformation. A birthmark or a growth, present at birth, which is composed of blood vessels that can cause functional or esthetic problems. Vascular malformations may involve multiple body systems. There are several different types of malformations, named after the type of blood vessel that is predominantly affected. Vascular malformations are also known as lymphangiomas, arteriovenous malformations, and vascular gigantism.
• Hemangioma. A type of birthmark; the most common benign (noncancerous) tumor of the skin. Hemangiomas may be present at birth (faint red mark) or appear in the first month after birth. A hemangioma is also known as a port wine stain, strawberry hemangioma, and salmon patch.
• Deformational (or positional) plagiocephaly. A misshapen (asymmetrical) shape of the head (cranium) from repeated pressure to the same area of the head. Plagiocephaly literally means ‘oblique head’ (from the Greek ‘plagio’ for oblique and ‘cephale’ for head).
The frequency of occurrence of cleft lip, with or without cleft palate, has been computed on a global scale and is estimated to be 1 in every 800 newborn babies (Tables 1-2 and 1-3). A child is therefore born with a cleft somewhere in the world approximately every two-and-half minutes. Accurate data on the frequency of occurrence of these disorders is relevant for implementing strategies aimed at primary prevention and effective management of these disabled children (Table 1-2). Like anywhere else, the epidemiological data in this situation is also inherently handicapped by:
Defining the affected population is also problematic because, on many occasions, the terminology is so vague that it is not clear whether it denotes all birth, or all live births. The word ‘births’ is again somewhat ambiguous because it usually includes stillbirths, a term which lacks clarity.
This was the most rigorously conducted study and it found the number of infants born every year with CLP to be 28,600; this means 78 affected infants are born every day, or three infants with clefts are born every hour (Table 1-4)!
CFA are not lethal but they are disfiguring, and thus cause a tremendous social burden. However, these disorders have an excellent outcome if surgical repair is carried out competently. Recent information regarding the etiology of CFA provides the means to carry out primary or secondary prevention. Maintaining a registry would be very useful as a benefit to the community and in reducing the burden of these anomalies, either by prevention or surgical repair.
Another reason why a registry would be desirable is the changing pattern of morbidity and mortality in India emerging as a result of the achievements in immunization, the success in providing primary health care and the existence of a well-developed health infrastructure. In many university and city hospitals congenital malformations and genetic disorders have become important causes of illness. All these reasons show that starting a registry of these disorders deserves high priority in India.
• About 10.9% of 459 cases of all clefts are syndromic in Chennai. Of these, about 50 % are due to single-gene disorders, about 18% due to chromosomal disorders, and the rest due to undetermined causes.
• There is some difference in the frequency of orofacial clefts in different states in India; however, this needs verification. The state of origin (or mother tongue) of the parents should be recorded.
The science of genetics is concerned with the inheritance of traits, whether normal or abnormal, and with the interaction of genes and the environment. This latter concept is of particular relevance to medical genetics, since the effects of genes can be modified by the environment.
|ACTC||Actin, Alpha, Cardiac Muscle|
|APP||Amyloid Beta A4 Precursor Protein (APP)|
|ARVCF||Armadillo Repeat Gene Deleted in VCFS|
|ATP&E||ATPhase, H+ Transporting, Lysosomal, Subunit E|
|CA1||Carbonic Anhydrase 1|
|CLTCL1||Clathrin, Heavy Polypeptide-Like 1|
|COL01A1||Collagen, Type I, Alpha-1|
|COL01A2||Collagen, Type I, Alpha-2|
|COL02A1||Collagen, Type II, Alpha-1|
|COL04A4||Collagen, Type IV, Alpha-4|
|COL04A5||Collagen, Type IV, Alpha-5|
|COL05A1||Collagen, Type V, Alpha-1|
|COL06A1||Collagen, Type VI, Alpha-1|
|COL10A1||Collagen, Type X, Alpha-1|
|CYLN2||Cytoplasmic Linker 2|
|DGSI||DiGeorge Syndrome Critical Region Gene|
|FGF8||Fibroblast Growth Factor 8|
|FGFR1||Fibroblast Growth Factor Receptor 1|
|FGFR2||Fibroblast Growth Factor Receptor 2|
|FGFR3||Fibroblast Growth Factor Receptor 3|
|GNAS1||Guanine Nucleotide-Binding Protein, Alpha-Stimulating Activity Polypeptide|
|GOLGA1||Golgi Autoantigen, Golgin Subfamily A, 1|
|GP1BB||Glycoprotein Ib, Platelet, Beta Polypeptide|
|GPR1||G Protein-Coupled Receptor 1|
|GTF2I||General Transcription Factor II-I|
|HIP1||Huntingtin-interacting Protein 1|
|HIRA||Histone Cell Cycle Regulation Defective, S. Cerevisiae, Homolog of, A|
|HOXD10||Homeo Box D10|
|MEOX2||Mesenchyme Homeo Box 2|
|MSX1||MSH, Drosophila, Homeo Box, Homolog of, 1|
|MSX2||MSH (Drosophila) Homeo Box Homolog 2|
|PTHR1||Parathyroid Hormone Receptor 1|
|RO60||Autoantigen Ro/SSA, 60–KD|
|SRC||V-SRC Avian Sarcoma (Schmidt-Ruppin A-2) Viral Oncogene|
|SRY||Sex-Determining Region Y|
|SSA1||Sjögren Syndrome Antigen A1|
|SSB||Sjögren Syndrome Antigen B|
|TNFRSF11B||Tumor Necrosis Factor Receptor Superfamily, Member 11B|
|TTPA||Tocopherol Transfer Protein, Alpha|
|TWIST||Twist, Drosophila, Homolog of|
|WBSCR1||Williams-Beuren Syndrome Chromosome Region 1|
Consideration of the heritability of a particular feature or trait requires a consideration of the relationship between genotype and phenotype. Genotype is defined as the genetic constitution of an individual, and may refer to specified gene loci or to all loci in general. An individual’s phenotype is the final product of a combination of genetic and environmental influences. Phenotype may refer to a specified character or to all the observable characteristics of the individual. The proportion of the phenotypic variance attributable to the genotype is referred to as heritability.
In specific traits, individual genotypes are readily identified and differences are qualitative (discrete), for example, the ABO blood antigen system. Gene frequencies can be estimated and the Mendelian type of analysis can be applied.
In continuous traits such as height, weight or tooth size, differences are characterized quantitatively between individuals. These quantitative traits in man are more elusive to study because they are determined by the alleles of many gene loci, and therefore, the Mendelian type of analysis is not appropriate. They are further modified by environmental conditions which obscure the genetic picture. If the genetic variation of a particular phenotypic trait is dependent on the simultaneous segregation of many genes and affected by environment it is referred to as being subject to multifactorial inheritance. Genetic differences caused by the segregation of many genes is referred to as polygenic variation and the genes concerned are referred to as polygenes. These genes are, of course, subject to the same laws of transmission and have the same general properties as the single genes involved in qualitative traits, but segregation of genes is translated into genetic variations seen in continuous traits through polygenes.
Different types of genetic ‘product’ can be thought of as being different distances from the fundamental level of gene activity. Enzymes, for instance, are almost direct products of gene action, and in most cases where genetic variation of enzyme structure has been demonstrated, it has been shown that a single locus is responsible for the structure of a single enzyme. The structure, and consequently, the activity of an enzyme is therefore usually simply and directly related to allele substitutions at a single locus.
Morphological characters, on the other hand, such as the numerous dimensions used to describe the shape of the face and jaws, are furthest removed from the fundamental genetic level and are the end results of a vast complexity of interacting, hierarchical, biochemical, and developmental processes. Each gene is therefore likely to influence many morphological characters so that a deleterious mutation, although producing a unitary effect at the molecular level, almost always results in a syndrome of morphological abnormalities. When a gene is known to affect a number of different characters in this way its action is said to be pleiotropic. A reverse hierarchy also exists, making each morphological character dependent on many different genes (Mossey, 1999).
All chromosomes exist in pairs so our cells contain two copies of each gene, which may be alike or may differ in their substructure and their product. Different forms of genes at the same locus or position on the chromosome are called alleles. If both copies of the gene are identical, the individual is described as homozygous, while if they differ, the term used is heterozygous.
The exception to the rule that cells contain pairs of chromosomes applies to the gametes, sperm and ovum, which contain only single representatives of each pair of chromosomes, and therefore, of each pair of genes. When the two gametes join at fertilization, the new individual produced again has paired genes, one from the father and one from the mother. If a trait or disease manifests itself when the affected person carries only one copy of the gene responsible, along with one normal allele, the mode of inheritance of the trait is called dominant (Fig. 1-1A). If two copies of the defective gene are required for expression of the trait, the mode of inheritance is called recessive (Fig. 1-1B).
The special case of genes carried on the X chromosome produces yet different pedigrees. Since male-to-male transmission is impossible and since females do not express the disease when they carry only one copy of the diseased gene (since it is modified by the homologous X chromosome), the usual pedigree consists of an affected male with clinically normal parents and children, but with affected brothers, maternal uncles, and other maternal male relatives (Fig. 1-1C). This mode of inheritance is described as X-linked recessive.
It has been long appreciated that many normal traits, such as height, intelligence, and birth weight, have a significant genetic component, as do a number of common diseases, such as diabetes mellitus, schizophrenia, hypertension, and cleft lip and palate. However, the pattern of inheritance of these traits does not follow the simple modes just described. Mathematical analysis of many of these has led to the conclusion that they follow the rules of polygenic inheritance, i.e. determined by a constellation of several genes, some derived from each parent.
The determination of heritability for polygenic or multifactorial characters is difficult, as a feature of continuous variation is that different individuals may occupy the same position on the continuous scale for different reasons. Using mandibular length as an example, micrognathia can occur in chromosomal disorders, such as Turner’s syndrome, in monogenic disorders such as Treacher Collins syndrome or Stickler syndrome, or due to an intrauterine environmental problem, such as fetal alcohol syndrome. Combined with this the concept of etiological heterogeneity encompasses the principle of the same gene defect producing different phenotypic anomalies, and syndromes can be due to defective gene activity in different cells. Conversely, different gene defects or combinations of defective genes can produce a similar phenotypic abnormality. Genetic lethality or reduced reproductive fitness can also complicate the diagnostic picture and genomic imprinting can result in a gene defect ‘skipping’ a generation. These complexities serve to hamper progress in the understanding of polygenic or multifactorial disorders such as orofacial clefting (Mossey, 1999).
In contrast to single-gene inheritance, either autosomal or sex-linked, the pedigree pattern does not afford a diagnosis of multifactorial inheritance. In multifactorial traits, the trait is determined by the interaction of a number of genes at different loci, each with a small, but additive effect, together with environmental factors (i.e., the genes are rendering the individual unduly susceptible to the environmental agents). Many congenital malformations (Table 1-6) and common diseases of adult life are inherited as multifactorial traits and these are categorized as either continuous or discontinuous.
Unstretched uterine and abdominal muscles
Small maternal size
Unusual implantation site
Other central nervous system malformations
Bilateral renal agenesis
Severe hypoplastic kidneys
Severe polycystic kidneys
Connective tissue defects
Source: MM Cohen Jr, The Child with Multiple Birth Defects. Raven Press, New York, 1982, p 10. Cited by RJ Gorlin, MM Cohen, LS Levin. Syndromes of the Head and Neck, 3rd Ed, Oxford University Press; 1990, New York.
The first sign of tooth development is a local thickening of oral epithelium, which subsequently invaginates into neural crest derived mesenchyme and forms a tooth bud. Subsequent epithelial folding and rapid cell proliferation result in first the cap, and then the bell stage of tooth morphogenesis. During the bell stage, the dentine producing odontoblasts and enamel secreting ameloblasts differentiate. Tooth development, like the development of all epithelial appendages, is regulated by inductive tissue interactions between the epithelium and mesenchyme (Thesleff, 1995).
There is now increasing evidence that a number of different mesenchymal molecules and their receptors act as mediators of the epithelial-mesenchymal interactions during tooth development. Of the bone morphogenetic proteins (BMPs) 2, 4, and 7 mRNAs shift between the epithelium and mesenchyme in the regulation of tooth morphogenesis (Aberg et al, 1997). The fibroblast growth factor (FGF) family have also been localized in epithelial and mesenchymal components of the tooth by immunohistochemistry (Cam et al, 1992); and in dental mesenchyme tooth development and shape is regulated by FGF8 and FGF9 via downstream factors MSX1 and PAX9 (Kettunen and Thesleff, 1998).
Homeobox genes have particular implications in tooth development. Muscle specific homeobox genes Msx-1 and Msx-2 appear to be involved in epithelial mesenchymal interactions, and are implicated in craniofacial development, and in particular, in the initiation developmental position (Msx-1) and further development (Msx-2) of the tooth buds (MacKenzie et al, 1991; Jowett et al, 1993). Further evidence of the role of Msx-1 comes from gene knock-out experiments which results in disruption of tooth morphogenesis among other defects (Satokata and Maas, 1994). Pax-9 is also transcription factor necessary for tooth morphogenesis (Neubuser et al, 1997). BMPs are members of the growth factor family (TGF) and they function in many aspects of craniofacial development with tissue specific functions. BMPs have been found to have multiple roles not only in bone morphogenesis, (BMP 5, for example, induces endochondral osteogenes is in vivo), but BMP 7 appears to induce dentinogenesis (Thesleff, 1995).
These are common, and mostly resolve spontaneously within the first few days of postnatal life. When they do not, further evaluation may be necessary to plan therapeutic interventions that may prevent long-term consequences. Approximately 2% of infants are born with extrinsically caused deformations that usually arise during late fetal life from intrauterine causes. Approximately 30% of deformed infants have two or more deformations. Deformed infants tend to show catch-up growth during the first few postnatal months after release from the intrauterine environment. The common deformations considered under the craniofacial category are nasal, auricular and mandibular deformities.
Teratogens are agents that may cause birth defects when present in the fetal environment. Included under such a definition are a wide array of drugs, chemicals, and infectious, physical, and metabolic agents that may adversely affect the intrauterine environment of the developing fetus. Such factors may operate by exceedingly heterogeneous pathogenetic mechanisms to produce alterations of form and function as well as embryonic and/or fetal death (Gorlin et al, 1990).
The mechanisms of teratogenesis are selective in terms of the target and effect. Thus, characteristic patterns of abnormalities can be expected to be associated with particular teratogenic agents. However, the extent to which an individual may be adversely affected by exposure to a given teratogen varies widely. This depends on the following four factors:
It is of considerable interest to the dental profession that experimental studies of teratogenic agents have almost invariably revealed a variety of head, neck and oral malformations. Conway and Wagner have compiled a list of the most common malformations of the head and neck as shown in Table 1-7.
Agnathia is a lethal anomaly characterized by hypoplasia or absence of the mandible with abnormally positioned ears having an autosomal recessive mode of inheritance. More commonly, only a portion of one jaw is missing. In the case of the maxilla, this may be one maxillary process or even the premaxilla. Partial absence of the mandible is even more common. The entire mandible on one side may be missing, or more frequently, only the condyle or the entire ramus, although bilateral agenesis of the condyles and of the rami also has been reported. In cases of unilateral absence of the mandibular ramus, it is not unusual for the ear to be deformed or absent as well. It is probably due to failure of migration of neural crest mesenchyme into the maxillary prominence at the fourth to fifth week of gestation (postconception). The prevalence is unknown and less than 10 cases are described. The prognosis of this condition is very poor and it is considered to be lethal.
Micrognathia literally means a small jaw, and either the maxilla or the mandible may be affected. Many cases of apparent micrognathia are not due to an abnormally small jaw in terms of absolute size, but rather to an abnormal positioning or an abnormal relation of one jaw to the other or to the skull, which produces the illusion of micrognathia.
True micrognathia may be classified as either congenital, or acquired. The etiology of the congenital type is unknown, although in many instances it is associated with other congenital abnormalities, including congenital heart disease and the Pierre Robin syndrome (q.v.) This form of the disease has been discussed by Monroe and Ogo. It occasionally follows a hereditary pattern. Micrognathia of the maxilla frequently occurs due to a deficiency in the premaxillary area, and patients with this deformity appear to have the middle third of the face retracted. Although it has been suggested that mouth-breathing is a cause of maxillary micrognathia, it is more likely that the micrognathia may be one of the predisposing factors in mouth-breathing, owing to the associated maldevelopment of the nasal and nasopharyngeal structures.
True mandibular micrognathia of the congenital type is often difficult to explain. Some patients appear clinically to have a severe retrusion of the chin but, by actual measurements, the mandible may be found to be within the normal limits of variation. Such cases may be due to a posterior positioning of the mandible with regard to the skull or to a steep mandibular angle resulting in an apparent retrusion of the jaw. Agenesis of the condyles also results in a true mandibular micrognathia.
The acquired type of micrognathia is of postnatal origin and usually results from a disturbance in the area of the temporomandibular joint. Ankylosis of the joint, for example, may be caused by trauma or by infection of the mastoid, of the middle ear, or of the joint itself. Since the normal growth of the mandible depends to a considerable extent on normally developing condyles as well as on muscle function, it is not difficult to understand how condylar ankylosis may result in a deficient mandible.
• Catel-Manzke syndrome
• Cerebrocostomandibular syndrome
• Cornelia de Lange syndrome
• Femoral hypoplasia—unusual facies syndrome
• Fetal aminopterin-like syndrome
• Miller-Dieker syndrome
• Nager acrofacial dysostosis
• Pierre Robin syndrome
• Schwartz-Jampel-Aberfeld syndrome
• van Bogaert-Hozay syndrome
Intrauterine acquired conditions
• Syphilis, congenital
• 49, XXXXX syndrome
• Chromosome 8 recombinant syndrome
• Cri du chat syndrome 5p
• Trisomy 18
• Turner’s syndrome
• Wolf-Hirschhorn syndrome
Mendelian inherited conditions
• CODAS (cerebral, ocular, dental, auricular, skeletal) syndrome
• Diamond-Blackfan anemia
• Noonan’s syndrome
• Opitz-Frias syndrome
Autosomal dominant conditions
• Camptomelic dysplasia
• Cardiofaciocutaneous syndrome
• CHARGE syndrome
• DiGeorge’s syndrome
• Micrognathia with peromelia
• Pallister-Hall syndrome
• Treacher Collins-Franceschetti syndrome
• Trichorhinophalangeal syndrome type 1
• Trichorhinophalangeal syndrome type 3
• Wagner vitreoretinal degeneration syndrome
Autosomal recessive conditions
• Bowen-Conradi syndrome
• Carey-Fineman-Ziter syndrome
• Cerebrohepatorenal syndrome
• Cohen syndrome
• Craniomandibular dermatodysostosis
• De la Chapelle dysplasia
• Dubowitz syndrome
• Fetal akinesia-hypokinesia sequence
• Hurst’s microtia-absent patellae-micrognathia syndrome
• Kyphomelic dysplasia
• Lethal congenital contracture syndrome
• Lethal restrictive dermopathy
• Marden-Walker syndrome
• Orofaciodigital syndrome type 4
• Postaxial acrofacial dysostosis syndrome
• Rothmund-Thomson syndrome
• Smith-Lemli-Opitz syndrome
• ter Haar syndrome
• Toriello-Carey syndrome
• Weissenbacher-Zweymuller syndrome
• Yunis-Varon syndrome
X-linked inherited conditions
• Atkin-Flaitz-Patil syndrome
• Coffin-Lowry syndrome
• Lujan-Fryns syndrome
• Otopalatodigital syndrome type 2
• Juvenile chronic arthritis
Macrognathia refers to the condition of abnormally large jaws. An increase in size of both jaws is frequently proportional to a generalized increase in size of the entire skeleton, e.g. in pituitary gigantism. More commonly only the jaws are affected, but macrognathia may be associated with certain other conditions, such as:
Cases of mandibular protrusion or prognathism, uncomplicated by any systemic condition, are a rather common clinical occurrence (Fig. 1-4). The etiology of this protrusion is unknown, although some cases follow hereditary patterns. In many instances the prognathism is due to a disparity in the size of the maxilla in relation to the mandible. In other cases the mandible is measur-ably larger than normal. The angle between the ramus and the body also appears to influence the relation of the mandible to the maxilla, as does the actual height of the ramus. Thus prognathic patients tend to have long rami which form a less steep angle with the body of the mandible. The length of the ramus, in turn, may be associated with the growth of the condyle. It may be reasoned, therefore, that excessive condylar growth predisposes to mandibular prognathism.
Figure 1-4 Macrognathia (prognathia) of the mandible. (A) The protrusion of the mandible is obvious. (B) The same patient after surgical correction (ostectomy) (Courtesy of Dr G Thaddeus Gregory and Dr J William Adams.
Surgical correction of such cases is feasible. Ostectomy, or resection of a portion of the mandible to decrease its length, is now an established procedure, and the results are usually excellent from both a functional and a cosmetic standpoint.
Hemihyperplasia is a rare developmental anomaly characterized by asymmetric overgrowth of one or more body parts. Although the condition is known more commonly as hemihypertrophy, it actually represents a hyperplasia of the tissues rather than a hypertrophy. Hemihyperplasia can be an isolated finding, but it also may be associated with a variety of malformation syndromes (Table 1-9). Almost all cases of isolated hemihyperplasia are sporadic.
• Beckwith-Wiedemann syndrome
• Neurofi bromatosis
• Klippel-Trenaunay-Weber syndrome
• Proteus syndrome
• McCune-Albright syndrome
• Epidermal nevus syndrome
• Triploid/diploid mixoploidy
• Langer-Giedion syndrome
• Multiple exostoses syndrome
• Maffucci’s syndrome
• Ollier syndrome
• Segmental odontomaxillary dysplasia
Hoyme et al (1998) provided an anatomic classification of hemihyperplasia:
Patients affected by facial hemihypertrophy exhibit an enlargement which is confined to one side of the body, unilateral macroglossia and premature development, and eruption as well as an increased size of dentition. Familial occurrence has been reported on a few occasions, according to the excellent review of the condition by Rowe, who described four additional cases. Of all reported cases, females are affected somewhat more frequently than males (63% versus 37%), according to the review by Ringrose. There is an almost equal involvement of the right and left sides.
The dentition of the hypertrophic side, according to Rowe, is abnormal in three respects: crown size, root size and shape, and rate of development. Rowe has also pointed out that not all teeth in the enlarged area are necessarily affected in a similar fashion. There is little information about the effects on the deciduous dentition, but the permanent teeth on the affected side are often enlarged, although not exceeding a 50% increase in size. This enlargement may involve any tooth, but seems to occur most frequently in the cuspid, premolars, and first molar. The roots of the teeth are sometimes proportionately enlarged but may be short.
Characteristically, the permanent teeth on the affected side develop more rapidly and erupt before their counterparts on the uninvolved side (Fig. 1-5). Coincident to this phenomenon is premature shedding of the deciduous teeth. The bone of the maxilla and mandible is also enlarged, being wider and thicker, sometimes with an altered trabecular pattern.
Figure 1-5 Facial hemihypertrophy.
The difference in the eruption pattern of the teeth on each side is apparent. The teeth on the affected side, where all deciduous teeth have already been lost, are not appreciably larger than those on the unaffected side (Courtesy of Dr John B Wittgen.
The tongue is commonly involved by the hemihypertrophy and may show a bizarre picture of enlargement of lingual papillae in addition to the general unilateral enlargement and contralateral displacement. In addition, the buccal mucosa frequently appears velvety and may seem to hang in soft, pendulous folds on the affected side.
There is no specific treatment for this condition other than attempts at cosmetic repair. Cosmetic surgery is advised after cessation of growth. Effect on life expectancy is not certain, but in some cases patients have lived a normal life span. Periodic abdominal ultrasound/ MRI is recommended to rule out tumors.
Facial Hemiatrophy (Parry-Romberg syndrome, Romberg-Parry syndrome, progressive facial hemiatrophy, progressive hemifacial atrophy)
Hemifacial atrophy remains almost as much an enigma today as it was when first reported by Romberg in 1846. Hemifacial atrophy, originally described by Parry and Henoch and Romberg consists of slowly progressive atrophy of the soft tissues of essentially half the face, which is characterized by progressive wasting of subcutaneous fat, sometimes accompanied by atrophy of skin, cartilage, bone and muscle. Although the atrophy is usually confined to one side of the face and cranium, it may occasionally spread to the neck and one side of the body and it is accompanied usually by contralateral Jacksonian epilepsy, trigeminal neuralgia, and changes in the eyes and hair. Evidence of a mendelian basis is lacking. Lewkonia and Lowry reported the case of a 16-year-old boy who developed facial changes at age seven and had localized scleroderma on one leg and the trunk. The presence of antinuclear antibodies in his serum suggested that the Parry-Romberg syndrome may be a form of localized scleroderma. Hemifacial atrophy is a form of localized scleroderma and is supported by its concurrence with scleroderma.
Hemifacial atrophy is a rare condition that occurs sporadically although some familial distribution has been found. The majority of cases are sporadic with no definite inheritance being proven in the literature.
The etiology has been the subject of considerable debate. Wartenburg considered the primary factor to be a cerebral disturbance leading to increased and unregulated activity of sympathetic nervous system, which in turn produced the localized atrophy through its trophic functions conducted by way of sensory trunks of the trigeminal nerve. Other workers suggested extraction of teeth, local trauma, infection and genetic factors could also be a cause. In a paper published in 1973, Poswillo attributed the development of facial deformities to the disruption of the stapedial artery. Poswillo fed pregnant rats with triazine and pregnant monkeys with thalidomide and showed the consistent maldevelopment of first and second branchial arch structures. Robinson, in 1987, supported Poswillo’s theory by demonstrating carotid flow abnormalities in two and defects related to vascular disruption in a third child with craniofacial microsomia.
Hemifacial atrophy is a syndrome with diverse presentation. The most common early sign is a painless cleft, the ‘coup de sabre,’ near the midline of the face or forehead. This marks the boundary between normal and atrophic tissue. A bluish hue may appear in the skin overlying atrophic fat.
The affected area extends progressively with the atrophy of the skin, subcutaneous tissue, muscles, bones, cartilages, alveolar bone and soft palate on that side of the face. In addition to facial wasting that may include the ipsilateral salivary glands and hemiatrophy of the tongue, unilateral involvement of the ear, larynx, esophagus, diaphragm, kidney and brain have been reported.
It starts in the first decade and lasts for about three years before it becomes quiescent. The final deformity varies widely, burning itself out in some patients with minimal atrophy, while in others progressing to marked atrophy.
Rarely, one half of the body may be affected. This condition may be accompanied by pigmentation disorders, vitiligo, pigmented facial nevi, contralateral Jacksonian epilepsy, contralateral trigeminal neuralgia and ocular complications.
The disease occurs more frequently in women; female to male ratio is 3 : 2. It has a slight predilection for the left side and appears in the first or second decades of life. It progresses over a period of two and 10 years, and atrophy appears to follow the distribution of one or more divisions of the trigeminal nerve. The resulting facial flattening may be mistaken for Bell’s palsy (Fig. 1-6).
Dental abnormalities include incomplete root formation, delayed eruption and severe facial asymmetry, resulting in facial deformation and difficulty with mastication. Hemiatrophy of the lips and the tongue is reported, as are dental effects. Foster has reported that growth of the teeth may be affected just as other tissues are involved. Eruption of teeth on the affected side may also be retarded.
In the preceding sections the conditions discussed are those in which there is an actual or apparent abnormal variation in size of one or both jaws. Of far greater importance than a simple disparity in size is the disparity in relation of one jaw to the other and the difficulties in occlusion and function that result.
A great many different types of malocclusion exist, and many classifications have been evolved in an attempt to unify methods of treatment. The classification of Angle, proposed in 1899, is the most universally known and used. That classification, with the approximate percentage occurrence as determined by Angle in a large group of orthodontic patients, is as follows:
Congenital lip pits and fistulas are malformations of the lips, often following a hereditary pattern, that may occur alone or in association with other developmental anomalies such as various oral clefts. Both Taylor and Lane and McConnel and his associates have emphasized that in 75–80% of all cases of congenital labial fistulas, there is an associated cleft lip or cleft palate, or both. The association of pits of the lower lip and cleft lip and/or cleft palate, termed van der Woude’s syndrome, has been reviewed by Cervenka and his associates.
Commissural pits are an entity probably very closely related to lip pits, but occur at the lip commissures, lateral to the typical lip pits. Everett and Wescott have described this entity and noted that it is also frequently hereditary, possibly a dominant characteristic following a Mendelian pattern, and may be associated with other congenital defects.
Many theories of the etiology of congenital lip pits have been offered, but none has been universally accepted. Pits may result from notching of the lip at an early stage of development, with fixation of the tissue at the base of the notch, or from failure of complete union of the embryonic lateral sulci of the lip, which persist and ultimately develop into the typical pits.
The lip pit or fistula is a unilateral or bilateral depression or pit that occurs on the vermilion surface of either lip but far more commonly on the lower lip (Fig. 1-7A). In some cases a sparse mucous secretion may exude from the base of this pit. The lip sometimes appears swollen, accentuating the appearance of the pits.
Commissural pits appear as unilateral or bilateral pits at the corners of the mouth on the vermilion surface (Fig. 1-7B). An actual fistula may be present from which fluid may be expressed. Whether this tract, either in lip or commissural fistulas, represents a true duct is not clear. Interestingly, in several cases preauricular pits have been reported in association with commissural pits.
van der Woude syndrome is an autosomal dominant syndrome typically consisting of a cleft lip or cleft palate and distinctive pits of the lower lips. The degree to which individuals carrying the gene are affected is widely variable, even within families. These variable manifestations include lip pits alone, missing teeth, or isolated cleft lip and palate of varying degrees of severity. Other associated anomalies have also been described.
The most prominent and consistent feature of van der Woude syndrome is orofacial anomalies. They are due to an abnormal fusion of the palate and lips, at days 30–50 postconception. The van der Woude syndrome can be caused by deletions in chromosome band 1q32, and linkage analysis has confirmed this chromosomal locus as the disease gene site. The gene has been localized to chromosome band 1q32. Further studies have raised the possibility that the degree of phenotypic expression of a gene defect at this locus may be influenced by a second modifying gene that has been mapped to chromosome band 17p11.
In general, van der Woude syndrome affects about 1 in 100,000–200,000 people. About 1–2% of patients with cleft lip or palate have van der Woude syndrome. The van der Woude syndrome affects both genders equally and no difference among them have been reported. The severity of the van der Woude syndrome varies widely, even within families. About 25% of individuals with the van der Woude syndrome have no findings or minimal ones, such as missing teeth or trivial indentations in the lower lips. Others have severe clefting of the lip or palate. The hallmark of the van der Woude syndrome is the association of cleft lip and/or palate with distinctive lower lip pits. This combination is seen in about 70% of those who are overtly affected but in less than half of those who carry the gene. The cleft lip and palate may be isolated. They may take any degree of severity and may be unilateral or bilateral. Submucous cleft palate is common and may be easily missed on physical examination. Hypernasal voice and cleft or bifid uvula are clues to this diagnosis. It is possible as well that a bifid uvula is an isolated finding in certain individuals with the van der Woude syndrome. The lower lip pits seen in this syndrome are fairly distinctive (Fig. 1-8). The pits are usually medial, on the vermilion portion of the lower lip. They tend to be centered on small elevations in infancy, but are simple depressions in adults. These pits are often associated with accessory salivary glands th/>