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X-linked dominant chondrodysplasia punctata (CDPX2), also known as Conradi-Hünermann-Happle syndrome, is a rare form of skeletal dysplasia that affects the skeleton producing short stature, asymmetric shortening of the limbs and scoliosis, as well as affecting the skin, hair and eyes. Frequency is unknown. The disorder is caused by mutations in the emopamil binding protein gene, EBP, the encoded protein of which normally functions as a delta(8)-delta(7) sterol isomerase in the cholesterol biosynthesis pathway catalysing the conversion of 8(9)-cholestenol to lathosterol. To date, over 50 separate familial and recurrent mutations have been reported with no obvious correlation between the molecular defects and the severity of the clinical phenotype. There is significant intrafamilial and interfamilial phenotypic variability in patients with EBP mutations. Affected patients require dermatological care, as regular emollient application improves skin scaliness. Scoliosis and limb asymmetry lead to premature arthritis, requiring orthopaedic input. Genetic counselling, diagnostic DNA and biochemical tests and possible prenatal diagnosis should be offered to all families. |