Fragile X syndrome is the most frequent cause of inherited mental retardation. It is caused by a dynamic mutation i.e. the progressive expansion of polymeric (CGG)n trinuleotide repeats located in the non coding region at the 5' end of the FMR1 gene at Xq 27.3. It is an X linked disorder; the manifestations are seen in all of carrier males and in 35% of carrier females. This type of mode of inheritance is described as X linked semidominant or X linked dominant with decreased penetrance.
The clinical features other than mental retardation include subtle dysmorphism, behavioral abnormalities and macroorchidism in postpubertal males. The phenotype being subtle, clinical diagnosis may be difficult especially in young children. Hence, testing all cases with mental retardation without obvious cause for fragile X syndrome is often the only way to identify fragile X syndrome cases. The parents and relatives of such a case need to be offered genetic counseling to prevent the recurrence of fragile X syndrome in the family. The cytogenetic and molecular diagnostic tests are available; the latter replacing the formers over the years. Polymerase chain reaction based tests are used for screening and Southern blot hybridization is the diagnostic test for detections of mutation and premutation. Prenatal diagnosis is possible by carrying out Southern blot hybridization on samples of chorionic villi or amniotic fluid. The complexities due to premutation and variable severity of manifestations in carrier females need to be understood while counseling families with fragile X syndrome.