Lucianne Cople MAIA1
Ivete Pomarico Ribeiro de SOUZA2
1Departamento de Saúde e Sociedade, Universidade
Federal Fluminense, Niterói, RJ, Brasil
2Departamento de Odontopediatria e Ortodontia, Faculdade de Odontologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
3Departamento de Pediatria, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
Braz Dent J (2000) 11(2): 153-160 ISSN 0103-6440
Introduction | Case Report | Discussion | Acknowledgments | Resumo | References
Craniometaphyseal dysplasia is a rare genetic bone remodeling disorder characterized by undertubulation of the long bones, especially in the lower extremities, causing deformities of the metaphyses of the long bones, and sclerosis of the skull base or cranial bone hyperostosis. The authors report a case of craniometaphyseal dysplasia in an 8-year-old Brazilian child, emphasizing the importance of precocious diagnosis of this rare genetic disorder.
Key Words: craniometaphyseal dysplasia, bone dysplasia, child.
Craniometaphyseal dysplasia (CMD) is a rare genetic bone remodeling disorder. Its main characteristics are undertubulation of the long bones, especially in the lower extremities causing deformities of the metaphyses in association with sclerosis or hyperostosis of the bones of the skull base (Schroder et al., 1992; Yamamoto et al., 1993; Rimseyer et al., 1993). Broadening of the short tubular bones with metaphyseal and diaphyseal abnormalities and, sometimes, diaphyseal expansion and widening of the ribs and clavicles (Langer et al., 1991) may also be observed in this syndrome.
There is very little laboratory data available on animal models for CMD, thus limiting knowledge on the physiopathogeny of this syndrome. Two possibilities have been suggested to explain the pathogenesis of the disorder: 1) bone reabsorption is reduced due to the dysfunction of osteoclasts; 2) bony overgrowth occurs secondarily to increased remodeling (Yamamoto et al., 1993).
It is therefore speculated that the cause of CMD is related to a functional abnormality of the local stroma cells which are incapable of differentiating osteoclast precursors in mature cells. It is known that not only in the autosomal dominant form, but also in the autosomal recessive form, the original problem is represented by a defect in the osteoclast, producing faults in reabsorption and remodeling of the secondary spongy substance (Smith, 1982). The recessive form is more severe than the dominant form, although in sporadic cases differentiation between the two forms is not possible (Carnevale et al., 1983). In the autosomal dominant type there is variable expressiveness, without sexual influence in phenotypical manifestations, with signs of inheritance between generations, while the autosomal recessive form can be considered poorly defined, heterogeneous, and difficult to diagnose (Beighton, 1995).
The purpose of this study is to present a case of craniometaphyseal dysplasia in an 8-year-old child followed up at the Pediatric Dentistry Clinic of the Federal University of Rio de Janeiro, emphasizing the importance of early diagnosis of this genetic disorder.
The patient, C.A.R., was referred to the Pediatric Dentistry Clinic of the School of Dentistry, Federal University of Rio de Janeiro by the Plastic Surgery Outpatient Department of the University Hospital of the same university, due to the serious state of her oral health. When she was seven years old, she underwent surgery to correct a palatine fissure.
This 8-year-old white female was the first child of nonconsanguineous healthy parents. Her birth was by cesarean section with cephalic presentation, normohydramnia, and normal placenta and umbilical cord. She weighed 3620 g at birth and her height was 53 cm.
The neonatal period elapsed almost normally, except that the mother noticed the presence of a cleft palate at home which was not diagnosed in the hospital nursery. At age 2 months, the child had a febrile convulsion episode. Since one year of age, the patient developed stomatitis concomitantly with bronchitis, but these ailments subsided in the last two years. Frequent episodes of otitis, tonsillitis and pneumonia occurred at age seven years.
According to her mother, C.A.R. held up her head at three months, sat at six and walked at fifteen months. At age one year, she began to utter her first words, and at age two years she already formed complete sentences. At present, she socializes well, speaks fluently although she has difficulty in pronouncing certain phonemes due to rhinophonia problems resulting from the palatine fissure. Her eyesight is considered normal, although there is bilateral conductive dysacusia with type B tympanometric profiles and no stapedial reflex in both ears. According to her family history, the patient has one normal brother, two paternal cousins with ocular hypertelorism and one paternal cousin with "pointed teeth".
On clinical examination, there was a presence of ocular hypertelorism, frontal bossing and a wide forehead, parietal protuberance, widening of the nasal ridge with an apparently small nose and in a saddle (Figure 1A), mandibular prognathism, low-set ears, the left ear having its helix folded over (Figure 1B), slightly arched legs with feet turning inward, and scoliosis.
Radiographic examination showed marked sclerosis of the skull base, the petrous region of the temporal with little sign of pneumatization in the mastoid region and less accentuated sclerosis of the cranial vault (Figure 2A). In addition, covering of the paranasal sinuses can be seen, principally the maxillary sinuses (Figure 2B). The cephalometric profile radiograph showed maxillary retrusion (ANB = -3°; SNA = 76°; SNB = 79°), which gives the patient a Class III Angle skeletal pattern, associated to vertical facial growth (axis Y = 71°) (Figure 2C). Radiographically, generalized demineralization was observed. Although the patient has not shown typical bone deformities in the metaphyseal regions of the tibias and distal regions of the femurs, there are irregular longitudinal sclerotic lines that are characteristic of metaphyseal dysplasias. Other abnormalities or the accentuation of the present abnormalities may appear in the future (Figures 2E and 2F).
During examination of the intraoral soft tissues, the presence of a nonsuppurative fistula was noted in the median palatine raphe region resulting from surgery to correct a fissure, partial tongue-tie and fistulated areas resulting from an odontogenic infection of the central and lateral incisors and second upper deciduous molars (Figure 1C). There were, also, amalgam restorations in the first left deciduous molar and in the second right deciduous molar, both of the lower arch and incipient carious lesions on the occlusal surface of the first left upper and right lower deciduous molars, as well as on the second left lower deciduous molar. The Class III Angle relationship was very clear of the first permanent molars and deciduous canines and the severe dental malocclusion (Figure 1D). Panoramic and periapical radiographs showed the anomalous formation of the roots of the deciduous molars, with an image suggesting lack of formation of the germ of the second left lower premolar. (Figures 1E-F and 2D).
Information obtained during the anamnesis, as well as the clinical characteristics, raised a doubt about the presence of a genetic syndrome. Based on the heredogram (Figure 3), the phenotypic expression and according to the severity of the case, an autosomal dominant inheritance of CMD could be suggested, possibly of sporadic mutational origin.
The autosomal dominant form of craniometaphyseal dysplasia is characterized by good general health, normal stature and intelligence and the absence of systemic ramifications; the bones are not fragile and there is no lack of hematopoiesis (Reardon, 1991). The facial distortions include mandibular prognathism, dental malocclusion, ocular hypertelorism, depression of the paranasal bones, a relatively small nose, narrowing of the upper airway, producing chronic rhinitis caused by nasal obstruction and, consequently, mouth breathing (Millard, 1967; Smith, 1982; Beighton, 1995; McKusick, 1996). Some of these clinical characteristics can be identified in the patient of this report (Figures 1A-B).
In radiographs of CMD patients, it is possible to see diffuse cranial involvement with skull base sclerosis, calvaria, petrous portion and cranial sutures, obliteration of the nasal sinuses, variable absence of pneumatization of paranasal and mastoid sinuses, depression of the paranasal bones, ocular hypertelorism in childhood, which tends to regress in adulthood, as well as mandibular prognathism and facial asymmetry. There may also be widening of the metaphyses of the long bones, fine corticals without bone sclerosis, normal spinal column and pelvis, clavicles and condrochondral junctions with few remodeling defects (Smith, 1982; Key et al., 1988; Beighton, 1995). According to Millard (1967), the long bones are fine and their radiolucency gives a false impression of osteoporosis.
In the patient of this report, sclerosis of the skull base can be seen, and the petrous region of the temporal bone shows clear absence of pneumatization of the mastoids (Figures 2A-C), covering of the paranasal sinuses, especially the maxillary sinuses (Figure 2B), a remodeling defect of the long bones and alterations in the metaphyses (Figures 2E-F). The presence of these characteristics bears out the diagnosis of CMD in this patient.
According to Carnevale et al. (1983) and Beighton et al. (1979), there is great variability in the phenotypical expression of CMD, which can explain the moderation in the abnormalities of the long bones of this patient.
According to Gorlin et al. (1978), the alterations of the temporal bone and of the nasal pyramid generally produce disturbances in perception and in sound conduction. The defect in auditive conduction can originate as much from compression of the 8th cranial pair, as from the frequent episodes of otitis and infection of the upper respiratory tract of bearers of this syndrome (Millard, 1967; Smith, 1982; Reardon et al., 1991; Beighton, 1995; McKusick, 1996), a fact confirmed by the patient's history.
The diagnosis of CMD in this patient was only possible due to characteristic radiographic findings. Similarly, the diagnosis differentiating it from other skeletic dysplasias, including metaphyseal dysplasia, craniodiaphyseal dysplasia, frontometaphyseal dysplasia, among others, was based on specific radiographic characteristics (Schroder, 1992; Rimseyer et al., 1993).
Gorlin (1978) reports that there is much confusion about the differentiation of the genetic disorders characterized by remodeling errors of the tubular and cranial bones. Nonetheless, in spite of the similarities between the disorders, the differences between them can be noted. Many of the characteristics of CMD are present in metaphyseal dysplasia (Pyle disease), although in the latter there are no orofacial manifestations nor manifestations in the skull base (Beighton, 1995). This fact on its own rules out the possibility of this syndrome in the patient of this report, because the regions mentioned are clearly affected. In craniodiaphyseal dysplasia the extent and anatomical distribution of the disorder are the source for differentiation (Beighton, 1995). In addition, craniodiaphyseal dysplasia can be considered a serious bone disorder characterized by hyperostosis and massive sclerosis which particularly affects the skull and facial bones and is associated to mental retardation, convulsions, visual insufficiency, deafness, retarded growth and absence of sexual maturity. The severity of the case, as well as the involvement of metaphyses, excludes this type of disorder in the patient of this report, the same occurring with progressive craniodiaphyseal dysplasia (Key et al., 1988).
Frontometaphyseal dysplasia is a disorder of bone metabolism with X-linked inheritance, which results clinically in the protuberance of the supraorbital ridges, hypertelorism without thickening of the nose root and paranasal region, deficiency in mandibular growth, loss of hearing, genu recurvatum and unusual mental retardation. Radiographically, its principal characteristics are supraorbital thickening of the root of the nasal bones, of the skullcap and of the skull base, sinus obliteration, mandibular hypoplasia, narrowing of ribs, constriction of the pelvis and imperfections in the remodeling of the metaphyses (Reardon et al., 1991). Some of these characteristics, such as the protuberance of supraorbital ridges, mandibular hypoplasia, genu recurvatum, and defects in the ribs and pelvis, were not found in the patient, which excludes the possibility of this syndrome.
The importance of early diagnosis of genetic disorders must be emphasized to help the genetic counseling of parents of affected children and to answer questions about clinical and radiographic characteristics that are compatible with the presence of the disorder.
Although the diagnosis is not specifically the responsibility of dental
surgeons, they should monitor their patients so as to detect, as early
as possible, any clinical or radiographic signs that differ from normality,
aiming to better understand the etiopathogeny
of disturbances and, consequently, to conduct their clinical cases in a more rational way.
Our sincere gratitude goes to Professor Dr. Ieda Maria Orioli of the Genetic Medicine Department of the Federal University of Rio de Janeiro (UFRJ), to Cintia Parga V. da Silva, the Speech Therapist specializing in spoken language of the Pediatric Dentistry and Orthodontic Department, UFRJ, and to the Orthopedic Surgeon Fábio dos Santos Magalhães for his helpful collaboration in this work.
Maia LC, Modesto A, Carakushansky G, de Souza IPR: Displasia crânio-metafisária: relato de caso. Braz Dent J 11(2): 153-160, 2000.
A displasia crânio-metafisária é um distúrbio genético raro que afeta a remodelação óssea e pode ser caracterizada por uma infra-tubularização dos ossos longos, especialmente em suas extremidades inferiores, causando deformidades das metáfises dos ossos longos associada a esclerose da base do cânio ou hiperostose craniana. Os autores relatam um caso de displasia crânio-metafisária em uma criança brasileira de oito anos de idade, enfatizando a importância do diagnóstico precoce desta desordem genética rara.
Unitermos: displasia crânio-metafisária, displasia óssea, criança.
Beighton P: Craniometaphyseal dysplasia (CMD), autossomal dominant form.
J Med Gen 32: 370-374, 1995
Beighton P, Hamersma H, Horan F: Craniometaphyseal dysplasia - variability of expression within a large family. Clin Gen 15: 252-258, 1979
Carnevale A, Grether P, Del Castillo V, Takenaga R, Ozerchovski A: Autossomal dominant craniometaphyseal dysplasia. Clinical variability. Clin Gen 23: 17-22, 1983
Gorlin RJ, Pindborg JJ, Cohen Jr MM: Displasias e hiperostosis óseas craneotubulares. In: Sindromes de la cabeza y del cuello. 1st ed. Ediciones Jorary, Barcelona, p.121, 1978
Key Jr LL, Volberg F, Baron R, Anast CS: Treatment of craniometaphyseal dysplasia with calcitriol. J Ped 112: 583-587, 1988
Langer LO, Brill PW, Afshani E, Williams CA, Thomas IT, Frias JE: Radiographic features of craniometaphyseal dysplasia, wormian bone type. Skeletal Radiol 20: 37-41, 1991
McKusick VA: Mendelian inheritance in man. Catalogs of autossomal dominant, autossomal recessive, and X-linked phenotypes. The John's Hopkins University, CD-OMIM, 1996
Millard Jr RD, Batstone JHF: Craniofacial surgery in craniometaphyseal dysplasia. Am J Surg 113: 615-621, 1967
Reardon W, Hall CM, Dillon MJ, Baraitser M: Sibs with retardation, supraorbital sclerosis, and metaphyseal dysplasia, frontometaphyseal dysplasia, craniometaphyseal dysplasia, or a new syndrome? J Med Gen 28: 622-626, 1991
Rimseyer LT, Leonard JC, Stacy TM: Bone scan findings on craniometaphyseal dysplasia. Clin Nucl Med 18: 137-139, 1993
Schroder C, Guirin A, Oppermann HC, Oldigs HD: Craniometaphyseal dysplasia - characteristic roentgen findings. Klin-Padiatri 204: 174-176, 1992
Smith DW: Craniometaphyseal dysplasia syndrome. In: Recognizable Patterns of Human Malformation. Genetic, Embryologic, and Clinical Aspects. 3rd ed. WB Saunders, Philadelphia 1982
Yamamoto T, Kurihara N, Yamaoka K, Ozono K, Okada M, Yamakoto K, Matsumoto S, Michigami T, Ono J, Okada S: Bone marrow-derived osteoclastic-like cells from a patient with craniometaphyseal dysplasia lack expression of osteoclastic-reactive vacuolar proton pump. J Clin Invest 91: 362-367, 1993
Correspondence: Lucianne Cople Maia, Rua Lopes da Cunha, 145, Bloco 01, Aptº 704, Fonseca, 24120-090 Niterói, RJ, Brasil. Tel/Fax: +55-21-626-7002. E-mail: firstname.lastname@example.org
Accepted April 28, 1999
Eletronic publication october, 2000