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|IMAGES IN MEDICINE
|Year : 2001 | Volume
| Issue : 3 | Page : 204-5
S Gulati, M Kabra
Genetics Unit, Dept. of Pediatrics All India Institute of Medical Sciences, New Delhi - 110 029, India., India
Genetics Unit, Dept. of Pediatrics All India Institute of Medical Sciences, New Delhi - 110 029, India.
Source of Support: None, Conflict of Interest: None
Keywords: Adolescent, Case Report, Cleidocranial Dysplasia, diagnosis,genetics,Diagnosis, Differential, Human, Male,
|How to cite this article:|
Gulati S, Kabra M. Cleidocranial dysplasia. J Postgrad Med 2001;47:204
A 14-year-old boy presented with proportionate short stature (height 140 cm; Upper segment: Lower segment: 0.9:1), macrocephaly (head circumference 59.5cm), brachycephaly and prominent forehead. He had hypertelorism, depressed nasal bridge, mid-face hypoplasia (excluding malar region), narrow high-arched palate, delayed tooth eruption, enamel hypoplasia, long neck, narrow sloping shoulders, scoliosis, narrow thorax and absent clavicles [Figure - 1]. His hands had asymmetric length of fingers. He had conductive deafness and normal intelligence quotient. Chest X-ray revealed a narrow thorax with oblique ribs and absent clavicles [Figure - 2]. His CT head was normal. X-ray of skull revealed calvarial thickening especially over the occiput and incomplete development of the accessory sinuses. Other radiological findings included scoliosis without any associated vertebral anomalies, long second metacarpal, short middle phalanges of second and fifth fingers and short, tapering distal phalanges of both hands. A diagnosis of cleidocranial dysplasia was made.
Cleidocranial dysplasia is an autosomal dominant condition with generalised dysplasia of bone and teeth. A possible example of this disorder was detected in the skull of a Neanderthal man. The more obvious features of the defect in the clavicle and cranium prompted Marie and Sainton to utilise the term cleidocranial dysostosis for this condition. However, the more generalised dysplasia of bone and teeth has been emphasised, and the term cleidocranial dysostosis depicts only a portion of the abnormal development. Hence the term “dysostosis” has been abandoned in favour of “dysplasia”. Well over 500 cases have been reported.
The disorder is characterised by frontal and parietal bossing, brachycephaly, persistent open anterior fontanelle, and often with late closure of the other sutures (including the metopic suture). There may be macrocephaly. Associated with it is late or incomplete development of accessory sinuses and mastoid air cells, small sphenoid bones, calvarial thickening and wormian bones. Facial bones are small, mid-face hypoplasia with low nasal bridge, narrow high-arched palate, hypertelorism and conductive deafness may be seen. The primary dentition appears late and is frequently incomplete. The secondary dentition is similarly delayed and often malaligned with some teeth malformed and hypoplastic. Supernumerary teeth are common, especially in the premolar area. There may be associated enamel hypoplasia. Proportionate short stature may be seen.
The clavicles are either absent or severely hypoplastic which leads to abnormally low positioning of the shoulders that can frequently be opposed anteriorly well beyond the nipple line as seen in our patient [Figure - 1]. Thorax is narrow with short oblique ribs and the most serious manifestation is the occasional occurrence of a severe scoliosis. Hand anomalies may include asymmetric length of fingers. Other skeletal abnormalities include delayed mineralisation of public bone, wide symphysis pubis, narrow pelvis and spondylolysis.2,3 There may be syringomyelia or spina bifida occulta. Though there is slight to moderate shortness of stature, intelligence is usually normal.
Hearing and dental problems should be anticipated. Some authors believe that removal of deciduous teeth does not seem to hasten the eruption of permanent teeth and the permanent teeth may be difficult to extract because of malformed roots. Others believe that surgical exposure of impacted teeth in combination with removal of supernumerary teeth is helpful. Conventional orthodontic treatment and eventually auto transplantation of teeth may still be necessary in the future. Patients with this disorder need extensive dental therapy in order to maintain efficient chewing. A narrow pelvis may necessitate caesarean section in the pregnant female. A narrow thorax may lead to respiratory distress in early infancy., Our patient had classical features of this condition.
Autosomal dominant inheritance shows wide variability in expression, but usually showing a high penetrance. About one third of the cases represent fresh mutations. A gene for this disorder Osteoblast specific transcription factor 2 (Osf2)/Core binding factor activity 1 (Cbfa1) has been mapped to chromosome 6p21. Recent studies indicate that the transcription factor Osf2/Cbfa1 serves as a master gene regulating osteoblast-specific gene expression. The gene is expressed in the cells of the osteoblast lineage only, and this expression is regulated by calciotropic agents. There is no evidence of bone formation in animals that are homozygous for the deletion. Studies of heterozygotes indicate that there is severe reduction in the number of bone cells, the tissue is deficient in bone proteins, and the activity of enzyme alkaline phosphatase is low. They display phenotype similar to that seen in patients with cleidocranial dysplasia. In odontogenesis, Cbfa1 regulates key epithelial-mesenchymal interactions that control advancing morphogenesis and histo-differentiation of the epithelial enamel organ. Osf2 mutations include deletions, insertions and missense mutations. There are rare cases on record of possible autosomal recessive inheritance.
| :: References|| |
Recognizable Patterns of Malformation. In: Jones KL editor. Smith’s Recognizable Patterns of Human Malformation. 5th edn. Philadelphia: WB Saunders Company; 1997, pp 408-409. |
|2.||Marie P, Sainton P. Sur La dysostose cleido-cranienne hereditaire. Rev Neurol (Paris) 1898; 6:835-838. |
|3.||Jarvis JL, Keats TE. Cleidocranial dysostosis. A review of 40 new cases. Am J Roentgenol Radium Ther Nucl Med1974; 121:5-16. |
|4.||Jensen BL, Kreiborg S. Dental treatment strategies in cleidocranial dysplasia. Br Dent J 1992; 172:243-247. |
|5.||Shapiro IM. Discovery: Osf2/Cbfa1, a master gene of bone formation. Clin Orthod Res 1999; 2:42-46. |
|6.||D’Souza RN, Aberg T, Gaikwad J, Cavender A, Owen M, Karsenty G, et al. Cbfa1 is required for epithelial-mesenchymal interactions regulating tooth development in mice. Development 1999; 126:2911-2920.
[Figure - 1], [Figure - 2]
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