Arch Dis Child: first published as 10.1136/adc.38.202.632 on 1 December 1963. Downloaded from

Arch. Dis. Childh., 1963, 38, 632.

A CASE OF CHONDRODYSTROPHIA CALCIFICANS CONGENITA

BY SHEILA SINGH PAUL, P. L. RAO, P. MULLICK and P. KALLIANA From the Department ofPaediatrics, Kalavati Saran Children's Hospital, Lady Hardinge Medical College and Hospital, New Delhi, India

(RECEIVED FOR PUBLICATION MAY 28, 1963)

Chondrodystrophia calcificans congenita was first melia. Flexion deformities of the limbs are due to reported by Conradi in 1914 as chondrodystrophia muscle fibrosis involving commonly the knees and foetalis hypoplastica, at which time it was thought elbows. Limitation of movements of the joints are to be an atypical form of . It is a due to defects in articulation of the . Occa- rare form of chondrodystrophy (Nelson, 1959). sionally this is accompanied by pain and swelling. Fairbank in 1927 described two cases under the These infants are mostly weak, fail to thrive, are title 'dysplasia epiphysialis punctata'. Congenital subject to infections and are often mentally defective. stippled epiphyses is suggested as a better term by Associated anomalies may be seen such as poly- Jeune, Larbre, Carron and Couette (1953) for the dactyly, syndactyly, brachydactyly, congenital dys- reason that chondrodystrophy is present in some of plasia of the hips, vertebral wedging, kyphosis, high the cases but stippled epiphyses are found in all the arched palate, saddle nose, cleft palate, cretinoid by copyright. cases. facies, mongolism, umbilical and inguinal hernia The aetiology is obscure: it occurs sporadically and abnormalities of the cardiovascular and genito- and occasionally shows a familial tendency (Caffey, urinary system (Josephson and Oriatti, 1961). 1961; Jeune et al., 1953). Consanguinity has been Dyskeratotic types of skin changes with dryness, observed in some of the reported cases: a Mendelian seborrhoeic dermatitis and icthyotic hyperkeratosis, recessive mode of transmission is thought to be the incontinentia pigmenti and pilonidal cyst (Josephson most likely. Maternal illness during pregnancy has and Oriatti, 1961) are shown by 250% of the cases. been noticed in some of the cases. It is more Bilateral congenital cataracts are reported by common in prematures, and female children are Josephson and Oriatti in one-third of the cases, and affected three times as often as male (Sheach and in nine out of the 42 studied by Mosekilde (1952). http://adc.bmj.com/ Middlemiss, 1956), though Wenzl, Ivins and Stickler Cataracts may be seen at birth or delayed till 41 (1961) noticed an equal sex distribution. The months or later (Josephson and Oriatti, 1961). thyroid as a possible aetiological factor was sug- Bilateral optic atrophy with or without cataracts gested in six cases (Wenzl et al., 1961). Some has also been reported (Josephson and Oriatti, believe that a metabolic disorder is responsible as 1961). the condition is associated with bilateral cataract No significant biochemical changes have been

(Yakovac, 1954). noted. on September 24, 2021 by guest. Protected The condition is recognized clinically in the first The characteristic histological change is the focal few months or later in life. No record of a case deposition of lime in masses of degenerating con- reaching adult life can be found in the literature. nective tissue in the growing of both The disorder is congenital, affecting mainly cartilage, primary and secondary ossification centres (Wenzl muscle and eyes. In the very early months it may et al., 1961). The epiphysial cartilage and the be an accidental diagnosis (Wenzl et al., 1961). endochondral cartilage are well vascularized, These infants are dwarfs due to rhizomelia with there is mucoid degeneration with cartilage frag- severe shortening of humeri and femora, the former mentation and cyst formation, but whether the more than the latter. There is an asymmetry of primary defect is vascular or cartilagenous is not involvement which is unlike the symmetry of known. The mucoid degeneration and calcification achondroplasia. One limb involvement has been are not necessarily related. Calcification is followed described as dysplasia epiphysialis punctata mono- by breakdown, and removal is affected by fibro- 632 Arch Dis Child: first published as 10.1136/adc.38.202.632 on 1 December 1963. Downloaded from

CHONDROD YSTROPHIA CALCIFICANS CONGENITA 633 vascular tissue (Josephson and Oriatti, 1961). The proximal end of the tibia, the femur, humerus, the lens and cartilage have a high content of mucopoly- distal end of the tibia, the radius and ulna and both saccharide, lack an intrinsic blood supply and carry proximal and distal ends of the fibula are often on metabolic activity by a process of diffusion involved. Epiphyses about the elbow are commonly (Yakovac, 1954). involved in contradistinction to almost all the other Of the cases, 50% die of intercurrent infection dysplasias. The sacrum, entire vertebral column, before 1 year of age (Lane, 1960). Two clinical posterior ends of ribs and occasionally the aceta- forms are recognized. A severe type with marked bulum, ischium, sternum, scapula, tarsal and carpal generalized epiphysial involvement associated with bones, patella, hyoid bone, thyroid, larynx and other abnormalities. Cataracts in particular indi- tracheal rings may also be affected. Joint spaces cate a poor prognosis. The condition terminates and synovial membranes are not exempt from in death from overwhelming pulmonary and renal stippling. The long bones are often short and infection by 2 years of age. In a less severe variety thick with splayed ends and irregular epiphysial in which the lesion is limited to a single epiphysis lines. The proximal long bones, femora and or to one extremity with or without associated humeri are severely shortened. The joint spaces abnormalities, the prognosis is good: these children appear large due to large non-ossified epiphyses. may be left with a residual deformity that needs The vertebral column shows wedging or even corrective orthopaedic therapy years later. platyblasia with kyphosis as in Morquio's disease. From a survey of the published reports only Some of the longstanding extensive cases of coronal four cases have been followed beyond 41 years. cleft vertebra have been included in this condition. Selakovich and White (1955) report a case with The cruciate segmental appearance of the vertebral monomelic involvement followed for 11 years, bodies is suggestive of notochordal remnants. which resulted in shortening and hypoplasia of that Later the multiple stippling of the epiphyses tends to limb: Fairbank (1949) and Paul (1954) each followed fuse into single, smooth, flattened, well-outlined their cases for 9 years, and Wenzl et al. (1961) but deformed epiphyses (Lane, 1960). followed a case for 8 years and 3 months. All these cases were left with shortening of the limbs. Very Case Report by copyright. few cases reach adulthood. Perhaps milder cases may not be reported or not the A male baby Bittu was born normally on February 5, recognized and thus 1963, and admitted on March 22, 1963, to this hospital prognosis is undoubtedly better. for flexion deformities of both knee and elbow joints, which had been present since birth (Figs. 1, 2 and 3). Radiological Findings The 18-year-old mother had upper respiratory infection The characteristic radiological feature is the at the fifth and seventh months of pregnancy. The premature deposition of numerous, discrete, punc- father, 35 years of age, was healthy. No consanguinity tate calcific densities in the region of the developing was noted. There was no history of congenital abnor- malities in the family. epiphyses or preformed cartilage. The stippled On examination the baby was well nourished, weight http://adc.bmj.com/ densities are present before the normal time of 2,520 g., length 45 cm.; skull 33 cm. The skin of the appearance of the ossification centres. Occasionally cheeks and chin was rough, erythematous and scaling. stippling may surround a normal epiphysis or There was no cyanosis. Pulse rate 156 per minute, replace the epiphyses. The epiphyses of the respirations 48 per minute. The heart was not enlarged; on September 24, 2021 by guest. Protected

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FIGs. 1, 2 and 3.-Clinical photographs showing flexion deformities of both elbows and wrists. Note the equal length of second and third fingers and second and third toes on both sides. Arch Dis Child: first published as 10.1136/adc.38.202.632 on 1 December 1963. Downloaded from

-634 ARCHIVES OF DISEASE IN CHILDHOOD

FIG. 4.-Clinical photograph of eyes showing congenital bilateral cataract.

both sounds were normal. A systolic murmur was best heard in the third and fourth interspaces. Both eyes had cataracts. On dilating the pupil the left eye showed a large cataract filling the pupillary aperture (Fig. 4). The right eye had a cataractous lens which was displaced upwards. The red reflex could be seen through the aphakic portion. No details of the fundi could be made out. In the upper limbs the elbows reached down to the FIG. 6.-Skiagram of lateral view of knee joint showing clearly the

level of the nipple line. Both elbows and wrists were punctate stippling. by copyright. flexed at 30 degrees, but the latter could be passively fully extended. The thumbs were directed across the palm towards the ring fingers and the index and the middle fingers were of the same size. In the lower limbs the hips could not be abducted more than 20 X-ray Reports. (1) Antero-posterior view of chest degrees and could not be extended The fourth and shows lung fields clear. Cardiac size and contour are fifth toes of both feet were very short in length. Inves- not remarkable except for a questionable right ventricular tigations revealed a serum calcium 7 9 mg./100 ml.; dilatation. The ends of both humeri and the lower Hb 13-5 g., red blood cells 3 95 million/c.mm., white cervical and upper dorsal vertebrae show discrete blood cells 9,300/c.mm. Mother and baby were both punctate stippling. Rh positive. (2) Antero-posterior view of upper extremities shows http://adc.bmj.com/ characteristic stippling present at both ends of humeri and the distal ends of both radii (Fig. 5). The humeri are short with flaring of the proximal and distal ends. (3) Antero-posterior view of pelvis and lower extre- mities shows bilateral stippling around the hip joints, knee joints (Fig. 6) and ankle joints. The ischium shows similar changes. Both femora are shortened and the ends are flared. (4) Lateral view of the lower extremities shows on September 24, 2021 by guest. Protected stippling in the calcaneum as well. (5) Lateral view of skull shows that the bones of the cranial vault are normal. The lower cervical and upper dorsal vertebrae show the stippled appearance seen in the other bones. Summary A case of chondrodystrophia calcificans con- genita is reported. The baby had typical radio- FIG. 5.-Skiagram of right humerus showing the stippled epiphyses flexion of both upper and lower ends. Note shortening of humerus. logical findings, bilateral cataract, of elbows The left humerus also showed similar changes. and knees and deformities of fingers and toes. Arch Dis Child: first published as 10.1136/adc.38.202.632 on 1 December 1963. Downloaded from

CHONDROD YSTROPHIA CALCIFICANS CONGENITA 635 We wish to express our to Dr. S. Jeune, M., Larbre, F., Carron, R. and Couette, I. (1953). La maladie appreciation Kurup, congenitale des epiphyses pointillees. Arch. franc. Pediat., Ophthalmologist, Lady Hardinge Medical College and 10, 914. Hospital, for confirming our findings. We thank Josephson, B. M. and Oriatti, M. D. (1961). Chondrodystrophia Prof. M. Chaudhuri, Principal, Lady Hardinge Medical calcificans congenita. , 28, 425. College and Member-Secretary, Kalavati Saran Chil- Lane, J. W. (1960). Roentgenographic manifestations of the carti- dren's Hospital, for permission to publish this paper. laginous dysplasias. Amer. J. med. Sci., 240, 636. Mosekilde, E. (1952). Stippled epiphyses in the newborn and in infants. Acta radiol. (Stockh.), 37, 291. Nelson, W. E. (1959). Textbook of Pediatrics, 7th ed., p. 1237. Saunders, Philadelphia. REFERENCES Paul, L. W. (1954). Punctate epiphyseal dysplasia (Chondro- dystrophia calcificans congenita). Report of case with 9 year Caffey, J. (1961). Pediatric X-Ray Diagnosis, 4th ed., p. 885. Year period of observation. Amer. J. Roentgenol., 71, 941. Book Medical Publishers, Chicago. Selakovich, W. G. and White, J. W. (1955). Chondrodystrophia Conradi, E. (1914). Vorzeitiges Auftreten von Knochen- und calcificans congenita. Report of a case. J. Bone Jt Surg., eigenartigen Verkalkungskernen bei Chondrodystrophia fotalis 37A, 127 1. hypoplastica. Histologische und Rontgenuntersuchungen. Jb. Kinderheilk., 80, 86. Sheach, J. M. and Middlemiss, J. H. (1956). Dysplasia epiphysialis Fairbank, H. A. T. (1927). Some general diseases of the skeleton. punctata. Brit. J. Radiol., 29, 111. Brit. J. Surg., 1S, 120. Wenzl, J. E., Ivins, J. C. and Stickler, G. B. (1961). Punctate epi- - (1949). An atlas of general affections of the skeleton. 8. physeal dysplasia, another cause of leg length inequality. J. Dysplasia epiphysialis punctata. Synonyms-stippled epiphyses, Pediat., 59, 390. chondrodystrophia calcificans congenita. Hunermann. J. Bone Yakovac, W. C. (1954). Calcareous chondropathies in the newborn Jt Surg., 31B, 114. infant. Arch. Path., 57, 62. by copyright. http://adc.bmj.com/ on September 24, 2021 by guest. Protected