Screening for the fragile X syndrome among the mentally retarded: a clinical study

The fragile X syndrome is characterised by mental retardation with other fe atures such as a long face with large, protruding ears, macro-orchidism, an d eye gaze avoidance. This X linked disorder is caused by an expanded CGG r epeat in the first exon of the fragile X mental retardation (FMR1) gene whi ch is associated with shut down of transcription and absence of the fragile X mental retardation protein (FMRP). Molecular testing is used for detecti on of patients and carriers of the fragile X syndrome. In a screening programme for the fragile X syndrome in the south west of Th e Netherlands, 896 males and 685 females with an unknown cause for their me ntal retardation were scored on seven fragile X features. All were tested b y DNA analysis and 11 new cases were diagnosed. The seven item checklist al lowed exclusion from further testing in 86% of the retarded males (95% CI 0 .83-0.88) without missing either any of the newly diagnosed cases or, in re trospect, any of the 50 previously diagnosed cases known to our department. These results showed that clinical preselection for DNA testing in mentally retarded males is feasible using a simple scoring list, which will increas e the efficiency of further testing eightfold.