Fragile X syndrome and fragile XE mental retardation

There are two forms of mental handicap associated with fragile sites on the end of the long arm of the X chromosome. The well known common disorder Fragile X syndrome is associated with FRAXA and a rare non-specific form of mental handicap is associated with FRAXE. The cytogenetics of these fragile sites is considered. For Fragile X syndrome details are given of the molecular genetics, inheritance patterns, genetic counselling, methods for diagnosis of index cases, carrier detection and prenatal diagnosis. Series of prenatal diagnoses are briefly reviewed and technical and biological problems associated with this procedure are considered. Prenatal diagnosis of Fragile X syndrome using molecular genetic techniques is now a well established procedure, with the only significant problem being the inability to accurately predict phenotype in female fetuses with full mutations. Few prenatal diagnoses of Fragile XE non-specific mental retardation have been recorded. In principle the technical aspects of such a prenatal diagnosis should be little different from those for Fragile X syndrome. Incomplete knowledge of the phenotypic effect of the full mutation in males and females would make phenotypic prediction for any fetus shown to have such a mutation very difficult. At this stage all that could be determined with precision is that the mutation was present or absent in the fetus. Possible consequences of this are discussed.