CHILD syndrome caused by deficiency of 3β-hydroxysteroid-Δ8, Δ7- isomerase

Abstract

CHILD (congenital hemidysplasia, ichthyosis, and limb defects) syndrome is a rare, usually sporadic disorder associated with unilateral distribution of ichthyosiform skin lesions, limb defects, punctate calcifications of cartilaginous structures, and visceral anomalies. CHILD syndrome shares some manifestations with X-linked dominant Conradi-Hunermann syndrome (CDPX2), although the skeletal defects and skin lesions in CDPX2 are bilateral and asymmetric. Because CDPX2 patients have abnormal 8-dehydrosterol metabolism caused by mutations in 3β-hydroxysteroid-Δ8,Δ7-isomerase, we measured plasma sterols in a patient with CHILD syndrome and found levels of 8- dehydrocholesterol and 8(9)-cholestenol increased to the same degree as in CDPX2 patients. Subsequently, we identified a nonsense mutation in exon 3 of the patient's 3β-hydroxysteroid-Δ8,Δ7-isomerase gene. We speculate that at least some cases of CHILD syndrome are allelic with CDPX2 caused by 3β- hydroxysteroid-Δ8,Δ7-isomerase deficiency. (C) 2000 Wiley-Liss, Inc.