Screening for fragile X syndrome: a model for genetic disorders?

The merits of screening should be considered separately for each disorder

The fragile X syndrome is often cited as the commonest inherited cause of mental handicap. It was described after the finding that a fragile site at the distal end of the X chromosome was associated with mental handicap. The X linked inheritance pattern is atypical; female carriers may show some features, and males may also occasionally be asymptomatic carriers. Fragile X syndrome was the first of an increasing number of neurological genetic conditions in which a dynamic mutation of a triplet repeat was identified, where instability between generations explained the unusual inheritance pattern.1 The documentation of the molecular pathology in fragile X allowed confirmation of carrier status in both male and female family members. The growth in understanding of the condition led to early calls for screening,2 proposed both to implement early therapy and to reduce the birth prevalence.

Several approaches to screening are possible, broadly divided into either case finding with cascade screening (of relatives at risk in the extended family) or population …