X linked mental retardation and infantile spasms in a family: new clinicaldata and linkage to Xp 11.4-Xp22.11

In order to describe the neurological abnormalities and to identify the gen e localisation, we re-evaluated a previously reported family with X linked mental retardation (XLMR). Reliable data were obtained for six of the seven affected males, of whom two had had infantile spasms. Profound MR (IQ<20) was found in one and mild MR (IQ 50-70) in five males. No dysmorphic featur es, except for macrocephaly in one male, were found. Neurological abnormali ties included varying degrees of spinocerebellar involvement. Neuroimaging studies showed abnormalities, such as cerebellar atrophy or corpus callosum hypoplasia or both, in three of the six males. Several affected and unaffe cted subjects suffered from hyperhidrosis, which appeared to segregate inde pendently as an autosomal dominant trait. Genetic linkage analysis localise d the XLMR disease gene to Xp11.4-Xp22.11 with a maximum multipoint lod sco re of 3.57, overlapping the candidate region recently found in two Belgian XLMR-infantile spasm families. Compared to the Belgian patients, the majori ty of the affected males in this report had a considerably milder phenotype .