A novel missense mutation of NSDHL in an unusual case of CHILD syndrome showing bilateral, almost symmetric involvement.

The CHILD syndrome (MIM 308050), an acronym for congenital hemidysplasia with ichthyosiform nevus and limb defects, is an X-linked dominant trait with lethality for male embryos. Recently, we elucidated the underlying gene defect by demonstrating point mutations in NSDHL (NAD[P]H steroid dehydrogenase-like protein) at Xq28 in 6 patients with classic CHILD syndrome. The most striking clinical feature is an inflammatory nevus that usually shows a unique lateralization with strict midline demarcation. Ipsilateral defects involve all skeletal structures and internal organs such as the brain, the lung, the heart, or the kidney. As an exception to this rule, in some cases the CHILD nevus may occur in a more or less bilateral distribution. In 1997 Fink-Puches et al described a case of CHILD nevus with an almost symmetric arrangement. To test the correctness of the diagnosis, we now examined blood lymphocytes of this patient by single-strand conformation analysis and genomic sequencing. We identified a novel missense mutation in NSDHL that potentially may impair protein function. We conclude that a diagnosis of CHILD syndrome can be based on clinical features such as the highly characteristic morphology of the CHILD nevus. A symmetric distribution of this nevus can exceptionally be seen in patients with CHILD syndrome, and this bilateral involvement should not mislead the clinician to any other diagnosis. Apparently, the effect of random X-inactivation is responsible for different patterns of cutaneous involvement in female carriers of NSDHL mutations.