CHILD syndrome in 3 generations -: The importance of mild or minimal skin lesions

Background: CHILD syndrome (congenital hemidysplasia with ichthyosiform nevus and limb defects, Online Mendelian Inheritance in Mail 308050) is an X-linked dominant trait with lethality for male embryos. The disorder is caused by mutations in NSDHL (Online Mendelian Inheritance in Man 300275), a gene playing an important role in the cholesterol biosynthetic pathway. Most reports deal with sporadic cases, and only 5 cases of mother-to-daughter transmission have been documented. We present here a family with mild features of CHILD syndrome in 3 generations. Molecular analysis was used to confirm the diagnosis. Observations: We studied 14 members of a family with CHILD syndrome. The 23-year-old proposita, her mother, 2 aunts, and her grandmother presented with mild or minimal skin lesions that had been present since infancy. Analysis of the NSDHL gene showed missense mutation c.370G-->A in these 5 patients. This mutation was absent in the 9 clinically unaffected family members tested. Conclusions: In this family, we recognized CHILD syndrome with mild or minimal features in 3 generations because we were able to verify our clinical diagnosis by means of molecular analysis. We assume that many cases that so far have been considered sporadic may in fact be familial when a meticulous physical examination of female family members is combined with molecular testing.