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Dentomaxillary abnormalities in genetic diseases

Gabriela Lilios1, Lenuta Malcea2

Constanta, Romania

Summary

The purpose of this work is to identify the congenital bone diseases (as a result of the anomalies in the bone and joint system development), associated with dentomaxillary modifications. Objectives. Stating the etiology of congenital bone diseases, in order to anticipate dental problems, their prognosis and recurrence risk. Approaching various types of dental anomalies, their severity and degree of spreading in the most frequent congenital bone diseases. Identifying those bone syn- dromes, which benefit from etiopathogenic, general, orthopedic, surgical etc. treatment supporting the dental recovery effort. Methods. The survey is a five-angled approach of the most frequent congenital bone diseases relat- ed to dentomaxillary anomalies, bone general signs of the considered syndromes; etiology; type of related dentomaxillary modifications. Results. Genetic bone diseases are associated with dentomaxillary modifications, as common alter- ations occur ever since the embryonic stage. Enzymopathies, which result in the unmetabolized sub- stances storage, at bone level included, alter facial bones and dentition, as well. Determination of the type of bone disease, as well as the etiologic classification is necessary to anticipate dental mishaps, in order to determine their prognosis and recurrence risk. Conclusions. Disorders in the dentition development take on prevailing aspects in case of a certain bone disease, however they may co-exist. Etiopathogenic treatment improves the overall evolution of such diseases, supporting the dental recovery effort.

Key words: dentomaxillary anomalies, embryological development, bone, new-born.

Introduction embryologic stage entail dentomaxillary modifications. The survey approaches the issues on dentomaxillary modifications, their types, Material and Method complexity and spreading degree occurring in the bone and joint system development This work approaches the main bone anomalies. The purpose of our endeavor is signs of malformation syndromes (as sec- to identify the bone syndromes accompa- ondary to the anomalies in the bone and nied by dentomaxillary modifications, joint system development) and coexisting assuming that they have the same embry- dentomaxillary abnormalities, in descriptive ologic origin (Table 1), as alterations in the manner, as from the simultaneous and com-

1 Assoc. Prof., M.D., Department of Physiology, Faculty of Dental Medicine and Pharmacy, “Ovidius” University of Constanta 2 M.D., Pediatrician and Neonathologist, Clinical Hospital of Constanta

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Table 1. Embrionic development. and skeleton. (Jones, 1988)

Age Face Skeleton 24 days Hyoid arches 30 days Fusion, mandible, arches bud 34 days Leg bud Weeks Fetal development 7 1/2 Palatal swellings Cartilaginous models of bones Dental lamina Chondrocranium Epithelium Tail regression 8 Nares plugged Ossification center Sublingual gland 10 Lips Palate Joints 12 Dental papilla Tail degenerated Notochord degenerated. 16 Palate complete Distinct bones Enamel and dentine 24 Nares reopen Calcification of tooth primordial 38 Rudimentary frontal maxillary sinuses mon embryologic development of the skele- Etiology: the findings of a 2:1 female to ton and facial bones. male sex incidence have favored an X- The following are considered: linked dominant mode of determination. 1. congenital bone diseases frequently Treatment: Vitamin D therapy in a triggering dental abnormalities, as well as dosage of 25,000 to 100,000 units per day those where such alterations occur occasion- may be necessary. The therapy should be ally; discontinued every few years, because 2. more frequent types of dental modifi- spontaneous amelioration of the cations accompanying such syndromes; hypocalcemia may occur with time. 3. their etiology and transmission ways in order to determine their prognosis and 2. Chondroectodermal Dysplasia recurrence risk; Dentition: neonatal teeth; partial 4. possible related mental deficit; anodontia; small teeth, and/or delayed erup- 5. etiopathogenic, general, orthopedic, tion; dental problems are frequent. and surgical treatment. Etiology: Autosomal recessive. The majority of survivors are of normal Results intelligence.

I. Anodontia 3. Cleidocranial , a “consti- Frequent in: tutional”, generalized and symmetric dis- 1. Albright Hereditary Osteodystrophy ease. The more obvious feature is the defect Syndrome – in and cranium [2]. because of hypocalcemia and hyperphos- Abnormalities: craniofacial (brachy- phatemia that are unresponsive to parathor- cephaly with bossing; midfacial hypopla- mone [1]. Dentition: Delayed dental erup- sia); clavicle and chest (aplasia of clavicle; tion, aplasia and/or enamel hypoplasia. small ).

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Dentition: late eruption (especially the Etiology: autosomal recessive determi- permanent teeth). nation. Malformed roots; retention cysts; The artist Toulouse Lautrec is consid- enamel hypoplasia; supernumerary teeth. ered to have had pycnodysostosis. Etiology: autosomal dominant, with wide variability in expression. Occasional in: The patients have a normal intelligence. 1. Abnormalities: shallow orbits; prema- 4. Frontometaphyseal Dysplasia ture ; maxyllary hypopla- Abnormalities: craniofacial (coarse sia. face with prominent supraorbital ridges). Dentition is affected through maxillary Limbs (flexion defects of fingers, wrists, hypoplasia. elbows, , and ankles). Etiology: Autosomal dominant with Chest deformities, . variable in expression. About one quarter of Dentition: partial anodontia; delayed the reported cases have had a negative fami- eruption; retained deciduous teeth; high ly history. palate; small mandible. Etiology: X-linked with severe mani- 2. Oculo-dento digital Syndrome festations in male and variable but more Abnormalities: Eyes (microphtalmos, mildly affected females. microcornea, short palpebral fissures). Dentition: enamel hypoplasia. 5. Oto- palato digital Syndrome (Taybi Etiology: dominant autosomal determi- Syndrome) nation. The syndrome was initially described by Taybi in 1962. After that many cases have been recognized. II. Abnormalities: small stature; cranium Frequent in: (frontal and occipital prominence; absence 1. Chondroectodermal dysplasia of frontal and sphenoid sinuses); facial bone hypoplasia; limb (limited elbow extention). 2. Coffin Lowry Syndrome Dentition: partial anodontia; impacted Dentition: hypodontia; ; teeth. wide spaced teeth. Performance: mild mental deficiency Etiology: X-linked determination. The (IQ = 75-90). females have slight to moderate mental defi- Etiology: X-linked, semidominant. ciency.

6. Pycnodysostosis 3. Down Syndrome (trisomy 21 syn- In 1962, Maroteaux and Lamy drome). described the special condition (cleidocra- This syndrome has an incidence of nial dysostosis associated with osteosclero- 1/660 newborns making it the most common sis and bone fragility) as pycnosynostosis. pattern of malformation in man. Abnormalities: small stature; osteoscle- Abnormalities: general, CNS, craniofa- rosis; craniofacial (frontal and occipital cial, ears, neck, hands, feet, pelvis, cardiac prominence; delayed closure of sutures; etc. facial hypoplasia). Dentition: hypoplasia, irregular place- Dentition: irregular permanent teeth; ment, fewer caries than usual. partial anodontia; delayed eruption; caries. Performance. Mental deficiency (IQ =

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25-50 with an occasional individual above 50, the mean IQ for older patients is 24). Etiology. Trisomia 21. III. Enamel hypoplasia Types of chromosomal alteration of Frequent in: Down syndrome: full 21 Trisomy - 94 %; 21 1. Morquio Syndrome (Mucopolysa- Trisomy/normal mosaicism – 2.4 %; ccharidosis IV). translocations cases – 3.3 %; Mosaicism Deficiencies of two different enzymes usually leads to a less sever phenotype. leading to a severe form: mucopolysacchari- dosis IV A, and a mild form, mucopolysac- 4. Osteogenesis imperfecta, type I charidosis IV B. At least four type of osteogenesis Abnormalities: severe limitation of imperfecta exist. Osteogenesis imperfecta growth (adult stature 82 to 115 cm); cranio- associates dental disorders [3]. facial; skeletal and joints; marked Abnormalities: small stature; bones platyspondily; short, curved long bones, (thin cortices, small facial bones); joints and short stubby hands. ligaments; sclerae and skin; hearing. Dentition: widely spaced teeth with Dentition: hypoplasia of dentin and thin enamel that tends to become grayish in pulp with translucency of teeth; yellowish or color. bluish-gray coloration; susceptibility to Mentality is normal in both the severe caries; irregular placement; late eruption. and the mild forms. Natural History. There is wide individ- Etiology: autosomal recessive. ual variability. The long leg bones are the most frequent sites of breakage. After ado- 2. Pseudovitamin D Deficiency Rickets lescence, the likelihood of fractures dimin- There is a disease described by Prader ishes. By 30-39 years of age, 35% of in 1961. patients are deaf; by 60 years of age 50% of Metabolic: hypocalcemia, elevated patients are deaf. serum alkaline phosphatase. Etiology. Autosomal dominant. Dentition: enamel hypoplasia of post- Treatment. Long term calcitonin may be natal onset. beneficial in reducing the frequency of frac- Treatment. High doses of vit. D. The ture. Also, fluoride by yielding a stronger initial dosage of vit. D is 50,000-300,000 calcium apatite crystal may be beneficial. units per day. Maintenance dosage is 20,000-150,000 units per day. This disorder 5. Pycnodisostosis differs from X-linked hypophosphatemic rickets by virtue of having an earlier onset 6. Tricho-Dento-Osseous Syndrome with hypotonia, more severe hypocalcemia, Abnormalities: kinky hair at birth; less severe hypophosphatemia, and com- facies with frontal bossing, dolicocephaly; plete clinical and laboratory restitution on a bones with mild to moderate increased den- relatively high dosage of vit. D [4]. sity. 3. Vit. D-Resistant Rickets (X- linked Dentition: small, widely spaced; pitted hypophosphatemic Rickets) teeth with poor enamel; increased pulp Abnormalities: mild to moderate growth chamber size (taurodontism). deficiency (adult stature 130-160 cm). The teeth become eroded and discol- Metabolic: Hypophosphatemia with ored, are prone to periapical abscesses diminished renal tubular reabsorption of and/or lost by the second to third decade. phosphorus and calcium from gastro-intes- Etilogy: autosomal dominant. tinal tract; skeletal Rickets.

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Dentition: Large pulp chamber with Abnormalities: oral-artial clefts in mid- enamel hypoplasia; gingival and periapical upper lip, tongue, alveolar ridges, between infection; delayed eruption of dentition. premaxilla and lateral hard palate. Facial: Treatment. Vit. D taken in high dosage hyplopasia of allar cartilages, lateral place- is potentially more harmful than the untreat- ment of inner canthi. Digital: clinodactily, ed disease. Combined treatment with 1- syndactily, brachydactily. alpha hydroxyvitamin D and oral phosphate Dentition: dental caries, anomalies of has been successful. anterior teeth, absent lateral incisors. The ratio of female to male offspring of affected 4. Albright Syndrome women has been 2:1.

5. V. Early loss of teeth 1. Oculo-Dento-Digital Syndrome. 6. Oculo-dento digital Syndrome Dentition: enamel hypoplasia; early loss of teeth [7].

IV. Caries VI. Irregular placement of teeth. Frequent in: Frequent in: Down Syndrome; Gorlin 1. Cockayne Syndrome Abnormalities: Syndrome; Hurler Syndrome; Morquio growth deficiency with loss of adipose tis- Syndrome; Pycnodyostosis; Tricho-Dento- sue by mid to late infancy; craniofacial (salt Osseous Syndrome; Cohen Syndrome. and pepper retinal pigmentation, optic atro- Dentition: prominent maxillary central inci- phy). Dentition: carious teeth. sors; irregular placement of teeth. Performance: mental deficiency, weak- Occasional in: Crouzon Syndrome; ness, moderate perceptive deafness [5]. Ehler Danlos Syndrome; Maroteaux Lamy Etiology: Autosomal recessive. Syndrome.

2. Gorlin Syndrome (Basal Cell Nevus VII. Late eruption of teeth ( I , II , Carcinoma Syndrome) III, IV, V, VI, VII ). Abnormalities: craniofacial (bossing, broad nasal bridge); thorax; hands; skin; VIII. Neonatal teeth basal cell nevi over neck, upper , trunk Frequent in Chondroectodermal and face. Dysplasia Dentition: dyskeratotic cysts of mandible; occasionally ; caries of IX. Other tooth anomalies. teeth. Performance: variable mild to moder- Wide spaced in (Angelman Syndrome; ate mental deficiency. Coffin Lowry Syndrome; Hay Wells Etiology: autosomal recessive. Syndrome); Prominent teeth (Cohen Syndrome; Marshall Syndrome); 3. Tricho-Rhino-Phalangeal Syndrome Supernumerary (Gardner Syndrome; Oro- Abnormalities: mild growth deficien- Facial-Digital Syndrome); Large teeth cy; facial; hair, nails; skeletal. (XXX Syndrome). Dentition: small, carious teeth with dental malocclusion. Discussions Etiology: autosomal dominant [6]. Our research analyzes a group of syn- 4. Oral-Facial-Digital Syndrome dromes occurring in the bone and joint sys-

60 OHDMBSC - Vol. V - No. 4 - December, 2006 tem development anomalies, namely those development anomalies, usually displaying that entail the dentition alteration, including dominant transmission (autosomal or X- facial bones development abnormalities [8]. linked). This approach has been conducted at 4. And last, but not least, the fourth four essential levels: considered criterion focuses on the etiopath- 1. General, morphologic and function- ogenic and overall treatment that some of al aspects (mental deficit degree included) such diseases may take advantage from, as it for classification by categories of the bone supports the dental recovery effort, where development anomalies and determination necessary and appropriate [10]. of the kind of disease [1]. 2. The etiology of such syndromes is Conclusions either genetic (chromosomal, genetic), when lesions develop ever since the embryonic Bone diseases of genetic origin also stage, or enzymopathic, case in which it trigger modifications in dentition, as com- entails storage diseases or absorption – reab- mon alterations occur ever since the embry- sorption disorders, resulting in more or less onic stage. Enzymopathies, which result in severe bone modifications [9]. unmetbolized substances storage processes 3. The third approach criterion and the at the bone level, alter the facial bones and one this work lies on, is the type, degree of dentition as well. Determination of the type severity and spreading of dental lesions [6]. of bone disease, as well as the etiologic clas- Modifications of dentition have been clas- sification is absolutely necessary in order to sified according to the main type of disease: anticipate dental problems and determine hypodontia, enamel hypoplasia, dental cavities, their prognosis and recurrence risk. early loss of teeth, abnormal dental position, Disorders in dentition development take on delayed dental eruption, neonatal teeth. prevailing aspects in certain bone diseases, Although prevailing in certain syn- however in most cases such modifications dromes, such modifications usually associate coexist in the same syndrome. The same with a great diversity of dental disorders that dental lesion may also be found in several may be found in diseases, such as: congenital bone diseases. Etiopathogenic Cleidocranial dysplasia, Albright syndrome, treatment of some of the above-described Down syndrome, Osteogenesis Imperfecta etc. bone syndromes reduces the progress of In fact, such syndromes are most fre- bone lesions and supports the improvement quently found in the bone and joint system effort and possibly the dental recovery.

References 5. Geormaneanu M. Patologie indusa prenatal. Ed. Medicala Bucuresti, 1978; pp 388-404. 1. Nelson WE. Traite de Pediatrie. Septieme edition. 6. Shapiro F. Pediatric Orthopaedic Deformities. Librairie Maloine, 1962; pp 972-986. Diagnostic and Treatment. Medical School Harvard 2. Jones KL. Recognizable Patterns of Human Boston, 2001; pp 121-142. Malformation. Fourth Edition. WB Saunders 7. Leck I. Descriptive Epidemiology of Common Company, 1988; pp 690-698. Malformations. British Medical Bulletin, 1976; 3: 71- 3. Avroy A, Fanaroff M. Neonatal-Perinatal 75. Medicine. Diseases of the fetus and infant. Sixth edi- 8. Wrait McW. Overview of Bone Disease. Research tion. St Louis Mosby, 1997; pp 520-532. Nutrition Conference, 2003; pp 20-26. 4. Smith DV. Recognizable Patterns of Human 9. Hertzog ZI. EDP Bucuresti, 1996; pp 75-85. Malformation. Third edition. WB Saunders Company, 10. Mellors RC. Bone Disease. Weill Medical 1982; pp 456-475. College Cornwell University, 1999; 7: 45 - 49. Correspondence to: Dr. Lenuta Malcea, 144 Mircea Blvd., Bl. MD7A, Sc.B, Apt.48, Constanta, Romania. E-mail: [email protected]

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