X linked severe mental retardation, craniofacial dysmorphology, epilepsy, ophthalmoplegia, and cerebellar atrophy in a large South African kindred islocalised to Xq24-q27

To date over 150 X linked mental retardation (XLMR) conditions have been do cumented. We describe a five generation South African family with XLMR, com prising 16 affected males and 10 carrier females. The clinical features com mon to the 16 males included profound mental retardation (100%), mutism des pite apparently normal hearing (100%), grand mal epilepsy (87.5%), and limi ted life expectancy (68.8%). Of the four affected males examined, all had m ild craniofacial dysmorphology and three were noted to have bilateral ophth almoplegia and truncal ataxia. Three of 10 obligate female carriers had mil d mental retardation. Cerebellar and brain stem atrophy was shown by crania l imaging and postmortem examination. Linkage analysis shows the gene to be located between markers DXS424 (Xq24) and DXS548 (Xq27.3), with a maximum two point lod score of 3.10.