CHILD syndrome (congenital hemidysplasia with ichthyosiform nevus and limb defects, MIM 308050) is an X linked dominant, male lethal, multisystem birth defect characterised by an inflammatory epidermal nevus showing a unique lateralisation pattern and strict midline demarcation. Hypoplasia or aplasia of skeletal or visceral structures may be found ipsilateral to the major cutaneous involvement.¹ Owing to the highly characteristic clinical and histopathological features of the CHILD naevus,² a diagnosis can be established not only in classical cases (fig 1) but also in cases with minimal or atypical involvement.³ In 2000, mutations in NSDHL (NAD(P)H steroid dehydrogenase-like protein) at Xq28 were identified by some of us to be the cause of this syndrome.⁴ Four additional NSDHL mutations have subsequently been reported in individuals with CHILD syndrome.^5–8 Studies carried out on the murine Nsdhl mutants bare patches (Bpa) and striated (Str) have shown that this gene encodes a 3β-hydroxysteroid dehydrogenase (3β-HSD) that catalyses a step in the post-squalene cholesterol biosynthetic pathway and is localised within membranes of the endoplasmic reticulum and on the surface of intracellular lipid storage droplets.^9–11 Non-functional NSDHL might cause the CHILD phenotype through a lack of cholesterol or other sterols downstream of the block in biosynthesis, or by the accumulation of intermediates upstream of the product generated by NSDHL.

A related trait, X linked dominant chondrodysplasia punctata (CDPX2, MIM 302960),²² is caused by mutations in EBP (emopamil binding protein) at Xp11.22–p11.23 that functions similarly in the late cholesterol biosynthesis, downstream of NSDHL.^23,24 In the past, a case of X linked dominant chondrodysplasia punctata showing unilateral involvement …