Challenges in prenatal screening and counselling for fragile X syndrome.

Fragile X syndrome (FXS) is the most frequent cause of intellectual disability after Down syndrome. It is caused by the expansion of an unstable cysteineguanine-guanine (CGG) trinucleotide repeat on the 5’ untranslated region of the fragile X mental retardation-1 (FMR1) gene. In full mutation (FM), the expansion is >200 CGG repeats with aberrant methylation of the promoter region causing loss of the gene expression. Affected individuals display a spectrum of neurological, psychiatric, and developmental problems, as well as abnormal ophthalmological and facial features. Fragile X syndrome is an X-linked, dominant disorder. Although all males with a FM have FXS, only half of the females with a FM are clinically affected because of X-chromosome inactivation. The inheritance pattern of FXS is distinctive because a healthy woman who carries a pre-mutation (PM) or a mild expansion of 55-200 CGG repeats can pass on a FM to a child through mitotic expansion of the unstable PM allele. In Cheng et al’s article,1 two PM carriers (1 in 1325) and one FM carrier (1 in 2650) were detected in a sample of 2650 Hong Kong Chinese pregnant women. In Chinese children with unknown intellectual developmental disorder, the prevalence of FXS has been reported to be 0.93%.2 It would appear that FXS is not rare in the Chinese population.