[Genetic causes of mental retardation--diagnostic possibilities]

Mental retardation is a life-long disability occurring in 2-3% of all children. Genetic causes are very heterogeneous and the clinical presentation most often non-specific. Current diagnostic tools can only identify a specific aetiology in 50-70%, and more importantly, often do not exclude a genetic cause in apparently sporadic cases of mental retardation. A proven genetic aetiology has many implications for the extended family. Fragile X syndrome is the most prevalent cause of inherited mental retardation and occurs in 2-6% of both females and males. Chromosomes and fragile X syndrome should be routinely investigated in patients with mental retardation of unknown aetiology. Molecular cytogenetics (FISH) provide specific diagnosis of several rare and clinically recognizable syndromes. Provision of extended clinical information is critical at referral, so that the most relevant investigations may be selected. Biochemical and molecular investigations can be performed for an increasing number of distinct but all very rare conditions associated with mental retardation. Efficient methods for simultaneous investigation of a panorama of rare biochemical and molecular abnormalities are now available and might improve the diagnostic yield considerably in the near future. We recommend a long-term diagnostic follow-up which allows us to apply modern methods and diagnose syndromes with phenotypes developing over several years.