Non-specific X-linked mental retardation (MRX) is a very common disorder which affects approximately 1 in 600 males. Despite this high frequency, little is known about the molecular defects underlying this disorder, mainly because of the clinical and genetic heterogeneity which is evident from linkage studies. Recently, a collaborative study using the candidate gene approach demonstrated the presence of mutations in GDIalpha, a Rab GDP-dissociation inhibitor encoded by a gene localized in Xq28, associated with non-specific mental retardation.
to date the diagnosis of MRX is only considered in cases of typical X-linked familial recurrence. Extensive investigations should be carried to search for a potential recurrence in the families of all male patients presenting with isolated, permanent intellectual deficit for which no cause has been found. However, the natural history, severity and clinical aspect of MRX often vary from one sibling to another in a given family