Chondrodysplasia Punctata, Tibia-Metacarpal Type

For a general phenotypic description and a discussion of genetic heterogeneity of chondrodysplasia punctata, see CDPX2 (302960).

Clinical Features

Rittler et al. (1990) described 7 sporadic cases of what appeared to be a new form of chondrodysplasia punctata. Two of the cases had previously been reported by Burck et al. (1980) and Burck (1982). The principal clinical manifestations in all of the patients were flat midface and nose, short limbs, and otherwise normal development. Consistent radiologic manifestations in the newborn were discrete calcific stippling, coronal clefts of vertebral bodies, short tibias, and short second and third metacarpal bones. Radiologic findings in the older child included shortness of the tibias and of the third and fourth metacarpals. The same disorder was reported by Haynes and Wangner (1951) and by Asanti and Heikel (1963).

Savarirayan et al. (2004) reported long-term clinical and radiologic progression in 3 unrelated patients with the tibia-metacarpal form of chondrodysplasia punctata who had been followed for 37, 25, and 32 years, respectively. At follow-up, intellectual function was normal, physical function was well preserved, and there was marked resolution of several significant early radiographic features. Two patients had chronic serous otitis media during childhood which required tympanostomy tubes. One patient underwent lumbar laminectomy at age 26 for back pain related to spinal stenosis. One patient had hip dysplasia requiring orthopedic surgical intervention. All 3 had recurrent patella dislocation. Savarirayan et al. (2004) suggested that the long-term clinical and functional prognosis in this condition appears to be better than that expected based on initial clinical and radiologic findings.

Shukla and Phadke (2015) described a 1.5-year-old Indian boy, born of unrelated parents, with features suggesting a severe form of the MT type of chondrodysplasia punctata. The patient had a length of 63 cm (-7 SD), with a head circumference of 43 cm (50th centile). He had midface retrusion, depressed nasal bridge, short and proximally placed second digits, trident hand, and mild pectus carinatum. Radiographic features included severe shortening of the first, fourth, and fifth metacarpals, all the distal phalanges, and the proximal phalanx of the second digit of the hands, as well as severe shortening of the first, second, and third metatarsals and all the phalanges of both feet. Additional radiographic features included rounded vertebral bodies with decreased height, axe-shaped iliac bones, short humerus, distal ulnar hypoplasia, short and bent femur with widened metaphyses, and longer fibula that overshot the tibia at the upper end. There was stippling of the carpals, metacarpals, and phalanges, and punctate calcification in the sacral area.

Association with Maternal Systemic Lupus Erythematosus

Elcioglu and Hall (1998) reported 2 sibs with features consistent with a diagnosis of either the metacarpal or the brachytelephalangic type (see 302950) of chondrodysplasia punctata, one of whom was stillborn at 36 weeks and the other at 24 weeks, from a mother with systemic lupus erythematosus (SLE; 152700). Austin-Ward et al. (1998) reported a child with chondrodysplasia punctata and other congenital anomalies resembling those associated with the use of oral anticoagulants, but with no history of exposure, again born to a mother with SLE. Elcioglu and Hall (1998) and Austin-Ward et al. (1998), as well as Toriello (1998) in a commentary on these 2 papers, concluded that there was an association between chondrodysplasia punctata and maternal SLE.

Kozlowski et al. (2004) described 2 brothers with chondrodysplasia punctata, whose mother had longstanding lupus erythematosus and epilepsy, for which she had been treated with chloroquine and other therapeutic agents during both pregnancies. Kozlowski et al. (2004) pointed to 7 previously reported instances of the association between chondrodysplasia punctata and maternal SLE.

Inheritance

Of the 7 cases reported by Rittler et al. (1990), occurrence in both males and females, advanced paternal age in 1 case, and absence of parental consanguinity were compatible with autosomal dominant mutation.