Indian J Pediatr 1992; 59 : 633-642
CLINICAL BRIEFS
Cleidocranial Dysplasia : Underdiagnosed and Misdiagnosed ? L. Mehta and I.C. Verma
Genetics Unit, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi Cleidocranial dysplasia (CCD) is a generalised disorder of bone ossification, the most obvious sites of involvement being the skull and the clavicles. Two patients ,are described in whom a variety of disorders were considered before the diagnosis was made on the basis of the radiological features. It is pos sible that this is an underdiagnosed entity, because of its relatively benign clinical effects. It should be considered in the differential diagnosis of short stature with features of skeletal immaturity like abnormally large skull fontanella and Wonnian bones. CASE R E P O R T Cleidocranial dysplasia is an autosomal dominant condition which is well documented in literature since early times. Descriptions range from the Neanderthaloid skull found by Greig ~ to the affected Chinaman with seven wives whose descendants live in Cape Town, South Africa. Of 356, at least 70 descendants have been identified as affected2. It is probably commoner than realised, and could be underdiagnosed due to its relatively benign course and asymptomatic nature. Case 1 This girl presented at the age of 13 years with features of short stature and abnormality of the skull bones. Head circumference was 45 cm. and weight was 20 kg (all para-
meters well below the 3rd centile). There was hypertelorism, depressed nasal bridge, malar hypoplasia, high arched palate and large posteriorly rotated ears. Her skull had multiple depressed areas and there was a wide sagittal suture. Her neck appeared broad and shoulders were sloping. Heart, chest and abdomen were normal on exmnination. Iter assessed IQ was 75, dull average. Chromosome analysis (G banded) was normal. EEG was normal. Ultrasound abdomen showed normal ovaries, uterus, urinary bladder and kidneys. Provisional diagnosis made before the results of the investigations were available was Tumer's syndrome; on obtaining the ultrasound report, Noonan's syndrome was considered. Skeletal survey finally revealed file diagnosis. Skull x-ray film showed multiple Wonnian bones with widely open cranial sutures and unossified bones (Figures 1 & 2). Both clavicles were hypoplastic and thin, pelvis was narrow, with wide pubic symphysis. The radiological diagnosis was cleidocranial dysostosis. Retrospectively, the clinical features were classical of the condition. Teeth appeared normally but were small and irregular. On re-examining the family history, it appeared that the mother was short and had similar facial appearance. However, she had uncomplicated deliveries of her 8 children. She could not be examined. Two siblings who were available for examination showed no evidence of the disorder.
634
THE INDIAN JOURNAL OP ~'EI)IATRICS
~i~:~/i~84i
Vol. 59, No. 5
: : ' i/~i84
Fig 1 & 2. X-ray films of skull of case 1. Note extensive unossified areas, Wormian bones and open sutures.
Fig 1.
Fig. 4. X-ray film of pelvis of case 2. Note absent pubic rami and symphysis and hypoplastic ischial bones.
Case 2 Fig. 3. Chcst X-ray film of case 2 showing absent clavicles.
This girl presented at file age of 1 year and 9
MEHTA A N D VERMA : C L E I D O C R A N I A L DYSPLASIA
months with features of short stature, knock knees, chest and deformity. She was delivered by cesarian section at full term and had no medical problems of note. tter development was normal. She was the second of two sibs, born to a 24 year old mother and 29 year old father. Iter height was 73 cm, head circumference was 44.5 cm. Her anterior fontanelle was abnormally wide. Hypertelorism, depressed nasal bridge and epicanthic folds were present. She had prominent lower ribs and knock knees. Thyroid function, serum calcium, phosphate and alkaline phosphatase were normal. Skeletal survey was conclusive of cleidocranial dysplasia. The skull showed brachycephaly, wide fontanelles and sutures, with multiple wormian bones; mandibular symphysis was open. Both clavicles were absent (Figure 3). Pubic bones were unossified and lucent areas of defective ossification were seen in both femora and upper tibiae (Figure 4). The spine showed infantile, biconvex vertebral bodies. At 3 years age, on follow up her height was 85 cm, and weight was I0 kg. No dental abnormality could be detected. Deciduous teeth had appeared. No features of the disorder could be detected in the other family members. DISCUSSION The classical description of the osseous and dental abnormalities in CCD c,'une from Marie and Sainton in 1898. 3 A large survey of 505 cases by Lasker4 established the mode of inheritance as autosomal dominant. The term "dysostosis" implies abnormality of a particular single bone and in view of the generalised nature of the disorder, this has been discarded and the condition is now known as "cleidocranial dysplasia". There is a generalised failure of midline ossification resulting in the features of patent fon-
635
tanelle, metopic suture, nasal deformity, non union of the mandibular symphysis, bipartite hyoid, hypoplasia or absence of the clavicles, spina bifida and delayed closure of the pelvic symphysis5. It is probably commoner than realised; but in view of its generally asymptomatic nature, perhaps underdiagnosed. Problems for which medical attention may be sought include abnormal dentition, hearing loss, short stature and complications during child-birth due to pelvic abnormality. Patients may be prone to dislocations of the shoulder, hip and elbow joints. Final height attained by children with tho condition is reported to be significantly lower than their normal counterparts. 5 We have described two patients with cleidocranial dysplasia, both of whom have the classical features of the condition. However in both these children, the diagnosis came from the radiologist and not the clinician. In patient 1, the various conditions considered included Tumer's syndrome, Noonan's syndrome and in patient 2, hypothyroidism and other skeletal dysplasias. It would be worth considering this diagnosis in all patients with unossified skull bones or wide fontanella and cranial sutures. Examination of the clavicles and unusually easy approximation of the shoulders is usually confirmatory. Complete absence of the clavicles is noted in only about 10% of patients; while the commonest abnormality is absence of the central clavicular segment, with bony stumps at sternal and acromial ends. 6 The facial features of hypertelorism and maxillary hypoplasia are also sufficiently characteristic to strengthen the diagnosis. We have described these patients in order to highlight the fact that the condition can be missed by clinicians; tile radiological features are distinctive and as in our patients, the diagnosis comes after the Xray films are seen.
636
THE INDIAN JOURNAL OF PEDIATRICS
In both our patients, there is no clear evidence of affected family members. The mother of the first patient is said to have some of the facial features; however she has delivered 8 children with no complications. If at all, the disorder is probably mild in her. In favour of this patient having been affected by a new mutation, is tile paternal age of 53 years at the time of her conception. The second patient appears to be a new mutation. About 16% of cases of CCD are estimated to be sporadic rather than inherited. 6
REFERENCES 1. Greig DM. Neanderthaloid skull presenting features of cleidocranial dysostosis and
Vol. 59, No. 5
2.
3.
4. 5.
6.
other peculiarities. Edinburgh M J 1933; 40 : 497. Jackson WPU. Osteodental dysplasia (cleidocranial dysostosis). Acta Med Scandinav 1950; 139 : 292-307. Marie P, Sainton P. Sur la dysostose cleidocranienne hereditaire. Rev Neurol 1898; 6 : 835. Lasker GW. The inheritance of cleidocranial dysostos|s. Human Biol 1946; 18 : 103. Jensen B. Somatic development in cleidocranial dysostosis. Am J Med Genet 1990; 35 : 69-74. Forland M. Cleidocranial dysostosis: a review of the syndrome and report of a sporadic case with hereditary transmission. Am JMed 1962; 33 : 792-799.
Acro-osteolysis of Phalanges in a Case of Cystic Fibrosis A.K. Sarkar, S.K. Bag, S.K. Biswas and S.G. Saha Department of Pediatric Medicine, IPGME&R and SSKM Hospital, Calcutta Cystic fibrosis of the pancreas, now usually known simply as cystic fibrosis has been recognized clearly as a disease entity only since the late 1930s. Though it is considered to be the commonest inherited condition among populations in file so called developed countries,' it seems possible from recent reports 2,3 that file incidence among Pakistanis and Indians, most of whom are of caucasian race, is greater than has been suspected hitherto. Bhakoo et al 4 reported one case and Mehta et al 5 six clinical cases of cystic fibrosis in Indian children. The term acro-osteolysis should apply to instances in which the phalanges are affected exclusively. 6 Phalangeal forms are characterized primarily by the resorption of bone in
the terminal phalanges, though other portions may be affected. The rare association of acro-osteolysis in a case of cystic fibrosis prompted us to report tim case. CASE R E P O R T An eight and a half year old first female child of non-consanguinous well to do parents, was admitted in SSKM Hospital in August 1991, with complaints of recurrent hacking cough usually persistent, at times paroxysmal, often followed by vomiting since six months of age. The girl used to have frequent episodes of fever, nasal discharge, cough and respiratory distress for the same period. There was history of recurrent
CLINICAL BRIEFS
Cleidocranial Dysplasia : Underdiagnosed and Misdiagnosed ? L. Mehta and I.C. Verma
Genetics Unit, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi Cleidocranial dysplasia (CCD) is a generalised disorder of bone ossification, the most obvious sites of involvement being the skull and the clavicles. Two patients ,are described in whom a variety of disorders were considered before the diagnosis was made on the basis of the radiological features. It is pos sible that this is an underdiagnosed entity, because of its relatively benign clinical effects. It should be considered in the differential diagnosis of short stature with features of skeletal immaturity like abnormally large skull fontanella and Wonnian bones. CASE R E P O R T Cleidocranial dysplasia is an autosomal dominant condition which is well documented in literature since early times. Descriptions range from the Neanderthaloid skull found by Greig ~ to the affected Chinaman with seven wives whose descendants live in Cape Town, South Africa. Of 356, at least 70 descendants have been identified as affected2. It is probably commoner than realised, and could be underdiagnosed due to its relatively benign course and asymptomatic nature. Case 1 This girl presented at the age of 13 years with features of short stature and abnormality of the skull bones. Head circumference was 45 cm. and weight was 20 kg (all para-
meters well below the 3rd centile). There was hypertelorism, depressed nasal bridge, malar hypoplasia, high arched palate and large posteriorly rotated ears. Her skull had multiple depressed areas and there was a wide sagittal suture. Her neck appeared broad and shoulders were sloping. Heart, chest and abdomen were normal on exmnination. Iter assessed IQ was 75, dull average. Chromosome analysis (G banded) was normal. EEG was normal. Ultrasound abdomen showed normal ovaries, uterus, urinary bladder and kidneys. Provisional diagnosis made before the results of the investigations were available was Tumer's syndrome; on obtaining the ultrasound report, Noonan's syndrome was considered. Skeletal survey finally revealed file diagnosis. Skull x-ray film showed multiple Wonnian bones with widely open cranial sutures and unossified bones (Figures 1 & 2). Both clavicles were hypoplastic and thin, pelvis was narrow, with wide pubic symphysis. The radiological diagnosis was cleidocranial dysostosis. Retrospectively, the clinical features were classical of the condition. Teeth appeared normally but were small and irregular. On re-examining the family history, it appeared that the mother was short and had similar facial appearance. However, she had uncomplicated deliveries of her 8 children. She could not be examined. Two siblings who were available for examination showed no evidence of the disorder.
634
THE INDIAN JOURNAL OP ~'EI)IATRICS
~i~:~/i~84i
Vol. 59, No. 5
: : ' i/~i84
Fig 1 & 2. X-ray films of skull of case 1. Note extensive unossified areas, Wormian bones and open sutures.
Fig 1.
Fig. 4. X-ray film of pelvis of case 2. Note absent pubic rami and symphysis and hypoplastic ischial bones.
Case 2 Fig. 3. Chcst X-ray film of case 2 showing absent clavicles.
This girl presented at file age of 1 year and 9
MEHTA A N D VERMA : C L E I D O C R A N I A L DYSPLASIA
months with features of short stature, knock knees, chest and deformity. She was delivered by cesarian section at full term and had no medical problems of note. tter development was normal. She was the second of two sibs, born to a 24 year old mother and 29 year old father. Iter height was 73 cm, head circumference was 44.5 cm. Her anterior fontanelle was abnormally wide. Hypertelorism, depressed nasal bridge and epicanthic folds were present. She had prominent lower ribs and knock knees. Thyroid function, serum calcium, phosphate and alkaline phosphatase were normal. Skeletal survey was conclusive of cleidocranial dysplasia. The skull showed brachycephaly, wide fontanelles and sutures, with multiple wormian bones; mandibular symphysis was open. Both clavicles were absent (Figure 3). Pubic bones were unossified and lucent areas of defective ossification were seen in both femora and upper tibiae (Figure 4). The spine showed infantile, biconvex vertebral bodies. At 3 years age, on follow up her height was 85 cm, and weight was I0 kg. No dental abnormality could be detected. Deciduous teeth had appeared. No features of the disorder could be detected in the other family members. DISCUSSION The classical description of the osseous and dental abnormalities in CCD c,'une from Marie and Sainton in 1898. 3 A large survey of 505 cases by Lasker4 established the mode of inheritance as autosomal dominant. The term "dysostosis" implies abnormality of a particular single bone and in view of the generalised nature of the disorder, this has been discarded and the condition is now known as "cleidocranial dysplasia". There is a generalised failure of midline ossification resulting in the features of patent fon-
635
tanelle, metopic suture, nasal deformity, non union of the mandibular symphysis, bipartite hyoid, hypoplasia or absence of the clavicles, spina bifida and delayed closure of the pelvic symphysis5. It is probably commoner than realised; but in view of its generally asymptomatic nature, perhaps underdiagnosed. Problems for which medical attention may be sought include abnormal dentition, hearing loss, short stature and complications during child-birth due to pelvic abnormality. Patients may be prone to dislocations of the shoulder, hip and elbow joints. Final height attained by children with tho condition is reported to be significantly lower than their normal counterparts. 5 We have described two patients with cleidocranial dysplasia, both of whom have the classical features of the condition. However in both these children, the diagnosis came from the radiologist and not the clinician. In patient 1, the various conditions considered included Tumer's syndrome, Noonan's syndrome and in patient 2, hypothyroidism and other skeletal dysplasias. It would be worth considering this diagnosis in all patients with unossified skull bones or wide fontanella and cranial sutures. Examination of the clavicles and unusually easy approximation of the shoulders is usually confirmatory. Complete absence of the clavicles is noted in only about 10% of patients; while the commonest abnormality is absence of the central clavicular segment, with bony stumps at sternal and acromial ends. 6 The facial features of hypertelorism and maxillary hypoplasia are also sufficiently characteristic to strengthen the diagnosis. We have described these patients in order to highlight the fact that the condition can be missed by clinicians; tile radiological features are distinctive and as in our patients, the diagnosis comes after the Xray films are seen.
636
THE INDIAN JOURNAL OF PEDIATRICS
In both our patients, there is no clear evidence of affected family members. The mother of the first patient is said to have some of the facial features; however she has delivered 8 children with no complications. If at all, the disorder is probably mild in her. In favour of this patient having been affected by a new mutation, is tile paternal age of 53 years at the time of her conception. The second patient appears to be a new mutation. About 16% of cases of CCD are estimated to be sporadic rather than inherited. 6
REFERENCES 1. Greig DM. Neanderthaloid skull presenting features of cleidocranial dysostosis and
Vol. 59, No. 5
2.
3.
4. 5.
6.
other peculiarities. Edinburgh M J 1933; 40 : 497. Jackson WPU. Osteodental dysplasia (cleidocranial dysostosis). Acta Med Scandinav 1950; 139 : 292-307. Marie P, Sainton P. Sur la dysostose cleidocranienne hereditaire. Rev Neurol 1898; 6 : 835. Lasker GW. The inheritance of cleidocranial dysostos|s. Human Biol 1946; 18 : 103. Jensen B. Somatic development in cleidocranial dysostosis. Am J Med Genet 1990; 35 : 69-74. Forland M. Cleidocranial dysostosis: a review of the syndrome and report of a sporadic case with hereditary transmission. Am JMed 1962; 33 : 792-799.
Acro-osteolysis of Phalanges in a Case of Cystic Fibrosis A.K. Sarkar, S.K. Bag, S.K. Biswas and S.G. Saha Department of Pediatric Medicine, IPGME&R and SSKM Hospital, Calcutta Cystic fibrosis of the pancreas, now usually known simply as cystic fibrosis has been recognized clearly as a disease entity only since the late 1930s. Though it is considered to be the commonest inherited condition among populations in file so called developed countries,' it seems possible from recent reports 2,3 that file incidence among Pakistanis and Indians, most of whom are of caucasian race, is greater than has been suspected hitherto. Bhakoo et al 4 reported one case and Mehta et al 5 six clinical cases of cystic fibrosis in Indian children. The term acro-osteolysis should apply to instances in which the phalanges are affected exclusively. 6 Phalangeal forms are characterized primarily by the resorption of bone in
the terminal phalanges, though other portions may be affected. The rare association of acro-osteolysis in a case of cystic fibrosis prompted us to report tim case. CASE R E P O R T An eight and a half year old first female child of non-consanguinous well to do parents, was admitted in SSKM Hospital in August 1991, with complaints of recurrent hacking cough usually persistent, at times paroxysmal, often followed by vomiting since six months of age. The girl used to have frequent episodes of fever, nasal discharge, cough and respiratory distress for the same period. There was history of recurrent
