O07 CHILD syndrome and ILVEN: disorders on the same spectrum?

Abstract

Abstract Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects (CHILD syndrome) is a rare X-linked dominant disorder caused by hemizygous variants in the NSDHL gene. Typically, affected girls are born with unilateral skin lesions in a Blaschkoid distribution due to random X-inactivation, and ipsilateral limb reductions. We report a genetically confirmed case without significant limb reductions and consider the relationship of CHILD syndrome to inflammatory linear verrucous epidermal naevus (ILVEN) also sometimes caused by mosaic variants in NSDHL. A 9-month-old girl presented with extensive congenital red, scaly lesions in a Blaschkoid distribution confined to the right side of her body. Examination was otherwise normal apart from sensorineural deafness in the right ear and overlapping right 4th and 5th toes. Histology showed the characteristic foamy histiocytes of CHILD syndrome and genetic testing revealed a heterozygous pathogenic variant of NSDHL, c.262C>T p.(Arg88*) previously reported in CHILD syndrome. Patients clinically diagnosed with ILVEN but with NSDHL mutations have sometimes been reclassified as CHILD syndrome (König A et al. ILVEN encompasses a spectrum of inflammatory mosaic disorders. Am. J.Med.Genet. 2000;90:339-46). The histology of ILVEN is less specific than CHILD syndrome, without the characteristic foamy histiocytes. Nonetheless these conditions could be on a spectrum, with limb defects arising if mutant skin cells overlie the primitive limb bud (Moss C, Burn J. Hypothesis: CHILD+ILVEN=PEN or PENCIL J.Med.Genet. 1990;27:390-391). NSDHL controls cholesterol synthesis and the topical treatment with statins plus cholesterol effective in CHILD syndrome could be considered in some cases of ILVEN.