Pigmentary mosaicism, subcortical band heterotopia, and brain cystic lesions

A 10-year-old boy presented with a severe and diffuse mosaic skin hypopigmentation running (in narrow bands) along the lines of Blaschko associated with mosaic areas of alopecia, facial dysmorphism with midface hypoplasia, bilateral punctate cataract, microretrognathia, short neck, pectus excavatum, joint hypermobility, mild muscular hypotonia, generalized seizures, and mild mental retardation. Cranial magnetic resonance imaging revealed hypoplastic corpus callosum (primarily posterior), subcortical band heterotopia, and diffuse subcortical, periventricular cystic-like lesions. Similar dysmorphic features were observed in the child's mother, but with no imaging abnormalities. The facial phenotype coupled with the cysts in the brain was strongly reminiscent of the oculocerebrorenal Lowe syndrome. Full chromosome studies in the parents and the proband and mutation analysis on peripheral blood lymphocytes (and on skin cultured fibroblasts from affected and unaffected skin areas in the child) in the genes for subcortical band heterotopia (DCX (Xq22.3-q23)], lissencephaly (PAFAH1B1, alias LIS1, at 17p13.3), and oculocerebrorenal syndrome of Lowe (OCRL at Xq23-q24)] were unrevealing. This constellation of multiple congenital anomalies including skin hypopigmentation and eye, musculoskeletal, and nervous system abnormalities was sufficiently characterized to be regarded as a novel example of pigmentary mosaicism of the Ito type (i.e., hypomelanosis of Ito).