as first report ed by Martin of the disea nium prompt m Cleidocran ater on, it w plasia of bo m Cleidocran of the abnorm dysostosisâ h ysplasiaâ3. W d. Rarity of th.
TAJ December 2008; Volume 21 Number 2
ISSN 1019-8555 The Journal of Teachers Association RMC, Rajshahi
Case Report
Cleidocranial Dysplasia : A Case Report M Azizul Haque1, A R M Saifuddin Ekram2, M Durrul Huda3
Abstract Cleidocranial dysplasia is an autosomal dominant disorder with a wide range of expression, characterized by clavicular aplasia or hypoplasia, retarded cranial ossification, supernumerary teeth, short stature and a variety of other skeletal abnormalities. We are reporting a case of Cleidocranial dysplasia with literature is review. TAJ 2008; 21(2): 166-169
Assistant Professor, Department of Medicine, Rajshahi Medical College , Rajshahi. Professor, Department of Medicine, Rajshahi Medical College, Rajshahi. 3 Assistant Professor, Department of Radiology and Imaging, Rajshahi Medical College, Rajshahi. 1 2
Introduc ction Cleidocraanial dysplasiia (CCD) is an autosom mal dominant bone disord der with a wide range of expressionn, characterizzed by claviccular aplasia or ossificatioon, hypoplasiia, retarded cranial supernum merary teeth, short s stature and a a variety of other skelletal abnormaalities1. A poossible exampple of this disorder was detected in the skull off a Neanderthhal man. The condition waas first reportted by Meckeel in 1760 and d later reporteed by Martin in 1765. The more obvious features of the diseaase like defecct in the clav vicle and crannium promptted Marie andd Sainton to use the term m Cleidocranial 2 Dysostosiis for this co ondition . Laater on, it was w discovered that geneeralized dyspplasia of boone occurs in this condition n and the term m Cleidocrannial Dysostosiis depicts onlly a portion of o the abnorm mal developm ment. Hence the term “ddysostosis” has h been abaandoned in favor f of “dyysplasia”3. Well over 10000 cases have been b reportedd. Rarity of thhis disease prrompted us to o report the caase. udy Case stu A 17 year old male patient attended mediciine outpatientt departmentt with the complaints of growth reetardation. On n examinationn he was notted to have short s stature (height 1477 cm), bilaterral absence of o clavicles as a demonstratted by patiennt's ability to bring his sh houlders togeether, defectiive dentition in the form m of superum mery teeth and a failure of eruption of upper u and low wer incisors. He H had frontaal and parietaal bossing. His H anterior and a posterior frontalle werre still open. His chest was w narrow annd shoulders were slopingg. Examination of all otheer system rev vealed no abnnormality. Noone of his fam mily member has similar illness. Chest X Ray show wed absence of o clavicle inn right side and a hypoplasiia in left side, scapula andd glenoid caviity was smaall, and ribss were directed obliqueely downwardds. X Ray skull both view revealled widened skull suturees, presence of wormiian bones, froontalles are open, some of the teethhes were founnd missing an nd not erupteed. His cliniccal features and a investigaation findinggs matches the t classical description d off Cleidocraniaal Dysplasia. Discussion
CD gene has been mappedd to chromosoome 6 The CC p 214 within w a regioon containingg the CBFA1 gene, a mem mber of the Runt familyy of transcriiption factorss5. CBFA1 controls differentiation d n of precurrsor cells innto osteoblaasts and is thus essentiial for membrranous as weell as endochoondral bone formation, f whhich may be related to deelayed ossificcation of thhe skull, teeeth, pelvis and extrem mities in CCD D6 Typical cliinical findinggs are shownn in table 1.
Patieent can bring his h shoulders toogether becausee of abssence of claviclles
CXR Shoowing aplastic right clavicle and hypoplastiic lefft clavicle
X Raay Skull Showiing widened suutures, open frontanellles, wormian bones, b and defeective dentitionn
Craniofaccial growth is i affected inn many wayys. Head circcumference iss usually at the t upper lim mit without being b macroccephalic. Theere is a brooad forehead with frontal bossing b and some s degree of hypertelorrism. Closuree of the anterrior frontanellles and sagitttal and metop pic sutures iss delayed, oftten for life. Many M patientts with hypopplastic or evven
absentt clavicles have h gone thhrough life, even workinng as manuaal laborers, without disaability resultinng from thiis defect. Depending D onn the degreee of claviculaar hypoplasiaa, appearancee can range from a dimplle in the skin to sloping, almost a a the abillity to volunntarily absentt shoulders and bring the shoulders together. According A to most observvations, a com mplete absence of the claviicle(s) is rare, whereas hyypoplasia of thhe acromial end e is commoon7. Final heeight is signifficantly reducced in patientts with CC CD. Previous investigaations indicatte that birth length l is norm mal but that height h drops below b or arouund the 2nd centile c betweeen the ages of o 4 and 88,99. This is conncordant withh our patientt, who has a height of only o 147 cm.. In a study by Jensen,10 female patients were more affecteed than male patients. p Patieents usually have h a mildlyy disproportioonate short stature s with short limbs compared to the trunk, moore apparent in the upper limbs than thhe lower. Denntal changes occur frequently and are very characcteristic of CCD11. Retenttion of the deeciduous denttition with deelayed eruptioon of the peermanent teeeth is a relaatively constant finding. Dental D disabillity begins inn late youth with the proogressive morrbidity and looss of the deciduous denttition. Many patients p remeember living “without teeeth” for som me years until the permannent teeth eventually e errupted. Perm manent teeth show s a delaay of root deevelopment and a a lesseneed but not enntirely absent eruptive poteential. The situation s is further com mplicated byy the presennce of multiiple supernum merary teethh that displacce the deveeloping perm manent teethh and obstrucct their eruptiion.
Table 1: Clinical C and radiological r f features of Cleeidocranial dyysplasia7 Clinical Skull Brachycepphaly Frontal and parietal bossin ng Open suturres and frontaneelles Delayed cllosure of frontan nelles Relative prrognathism
Radiologgical Multiple wormian bones Segmental calvarial thickkening Un-ossifi fied sutures and patent p frontanellles Dysplastic changes in thee basiocciput Hypoplassia of maxilla Delayed mineralization
Soft skull in infancy Depressed nasal bridge Hypertelorism Thorax and shoulders Ability to bring shoulders together Narrow, sloping shoulders Respiratory distress at early age Increased mobility Pelvis and hips Caesarean section
Spine Scoliosis Kyphosis Hands Brachydactyly Tapering of fingers Nail dysplasia/hypoplasia Short, broad thumbs Clinodactyly of 5th finger Dentition Normal deciduous dentition Supernumerary teeth Delayed eruption Crowding, malocclusion
Conclusion CCD is very rarely encountered in clinical practice. This case is presented to show the significance of thorough clinical examination of patients with short stature including palpation of clavicles. References 1. 2.
3.
4.
Björn H, Grahnén H. Cleidocranial dysostosis. Odontol Revy .1966; 17:167-175. Recognizable Patterns of Malformation. In: Jones KL editor. Smith’s Recognizable Patterns of Human Malformation. 5th edn. Philadelphia: WB Saunders Company.1997; 408-409. Rimoin DL. International nomenclature of constitutional diseases of bone. J Pediatr. 1978; 93:614-18. Gelb BD, Cooper E, Shevell M, Desnick RJ Genetic mapping of the cleidocranial dysplasia (CCD) locus on chromosome band 6p21 to include a microdeletion. Am J Med Genet .1995; 58:200-205.
Calcification of nasal bone delayed or missing Hypoplastic sinuses (paranasal, frontal, mastoid) Hypoplastic, aplastic, or discontinuous clavicles Cone shaped thorax Cervical ribs, missing ribs Hypoplastic scapulae Delayed ossification of pubic bone Hypoplasia of iliac wings Widening of sacroiliac joints Large femoral neck, large epiphyses Hemivertebrae, posterior wedging Spondylolysis and spondylolisthesis Spina bifida occulta Short middle phalanges and metacarpals/tarsals III–V Hypoplastic distal phalanges Accessory epiphyses especially of 2nd metacarpal Long 2nd metacarpal
Impacted, supernumerary teeth
5.
Mundlos S, Otto F, Mundlos C, Mulliken JB, Aylsworth AS, Albright S, Lindhout D, Cole W G, Henn W, Knoll JH, Owen MJ, Mertelsmann R, Zabel BU, Olsen BR Mutations involving the transcription factor CBFA1 cause cleidocranial dysplasia. Cell .1997; 89: 773-779.
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Mundlos S, Cleidocranial dysplasia: clinical and molecular genetics. J Med Genet. 1999; 36: 177182.
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Jarvis JL, Keats TE. Cleidocranial dysostosis. A review of 40 new cases. AJR. 1974;121:5-16.
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Kempfle B. Dysostosis cleidocranialis. Zahnartz Z. 1965; 20:1364-9.
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Levin EJ, Sonnenschein H. Cleidocranial dysostosis. N Y State J Med .1963; 63:1562-6.
Dtsch
10. Jensen BL. Somatic development in cleidocranial dysplasia. Am J Med Genet .1990; 35:69-74. 11. Jensen BL, Kreiborg S. Development of the dentition in cleidocranial dysplasia. J Oral Pathol Med .1990; 19:89-93. All correspondence to: M Azizul Haque
Assistant Professor Department of Medicine Rajshahi Medical College Rajshahi.
