Clinical features of boys with fragile X premutations and intermediate alleles

Fragile X syndrome has a characteristic behavioural and physical phenotype. Clinical experience and case reports suggest that boys with premutations and intermediate alleles may have similar, but possibly milder, clinical features than those with the full mutation. We conducted detailed physical, psychiatric, psychological and speech and language evaluations on a clinical series of 10 boys, with either premutation or intermediate CGG triplet expansions. Wherever possible we measured the levels of FMR1 protein in participants' hair roots. Many participants demonstrated striking resemblance in their clinical picture, behavioural and physical, to individuals with the fragile X syndrome full mutation. However, protein expression was normal in all participants where it was assessed, despite large variation in CGG triplet repeats. We propose that the findings are unlikely to be attributable to ascertainment bias alone. Replication on larger independent samples is required to confirm our impression that fragile X premutations and intermediate alleles may be associated with important developmental disabilities and physical features.