In genetic counseling, it is important to distinguish this autosomal dominant type from the clinically similar X-linked dominant type, which is fatal in hemizygous males. Severely affected infants are either stillborn or die soon after birth. Prognosis for survival is relatively good for those less severely affected. The Conradi-Hünermann type is X-linked recessive affecting Xp22 and the arylsulfatase E (ARSE) gene.

Clinical Manifestations. The major signs are usually evident at birth: a head of average circumference with a distinctive flat facies, mildly flattened nasal bridge, relatively short neck, and asymmetric shortening of the limbs. By early childhood, the characteristic facies largely disappears but the limb asymmetry may need surgical correction. Congenital cataracts are seen in about 18% of cases. Scoliosis is common after age 1; joint contractures occur later. The skin is often dry, scaly, and atrophic. The ichthyosiform skin changes and alopecia usually persist into adulthood. Adult height is 51 to 63 inches.

Radiographic Findings. Early signs consist of punctate calcifications in the vertebral column and the epiphyses of the long bones and the carpal, tarsal, and pelvic bones, usually in asymmetric distribution. The metaphyses are intact, but the epiphyses frequently become dysplastic (flattened, small, or irregularly shaped).

RHIZOMELIC TYPE

Rhizomelic-type chondrodysplasia punctata has an autosomal recessive inheritance and is more severe than the Conradi-Hünermann or X-linked dominant type. The PEX7 gene is affected, which encodes the protein peroxin 7. Recurrent infections usually cause death in the first year of life. Survivors have a high incidence of profound psychomotor retardation and other neurologic abnormalities, such as spastic quadriparesis.

Clinical Manifestations. The features of rhizomelic-type chondrodysplasia punctata are the same as those of the Conradi-Hünermann type, but the rhizomelic shortening of the limbs is more severe and congenital cataracts are extremely common. Microcephaly, contractures, and postnatal failure to thrive are also typical.

Radiographic Findings. The epiphyseal and extraepiphyseal calcifications are usually severe, with a symmetric distribution sparing the vertebral column. Lateral radiographs reveal vertical coronal clefts of the vertebral bodies. In the humerus and/or femur, severe shortening, splaying, and metaphyseal cupping are characteristic.

X-LINKED DOMINANT TYPE

Approximately 25% of reported cases of chondrodysplasia punctata are probably transmitted as an X-linked dominant trait. This results in a mutation in the emopamil-binding protein and alters the effects on the cholesterol biosynthesis pathway. Most patients are female, and the disorder is usually fatal in males.

Clinical Manifestations. This disorder shares many features with the Conradi-Hünermann type, with hypoplasia of the distal phalanges a distinctive trait. Pathognomonic cutaneous findings in the first months of life include erythematous skin changes and striated ichthyosiform hyperkeratosis. Patterned ichthyosis, coarse and lusterless hair, and cicatricial alopecia become evident later. A variable severity, marked asymmetry of long bones, and cataracts are thought to be consistent with functional X-chromosome mosaicism in females.