Abstract

Rett syndrome is a severe neurodevelopmental condition, currently diagnosed by application of recently revised clinical criteria.[1] Since the discovery in 1999 of the association between MECP2 mutations and Rett syndrome,[2] there has been considerable research into the relationship between genotype and phenotype in this disorder. This research has been able to link a number of the more common mutations to milder or more severe clinical features or to specific Rett syndrome variants.[3, 4, 5] In addition to the common point mutations (p.R106W, p.R133C, p.R168X, p.R255X, p.R270X, p.R294X, p.R306C and p.T158M) of MECP2 which are present in between 60% to 70% of cases with pathogenic MECP2 mutations,[3, 4, 6, 7] deletions in the C-terminal region have been reported in approximately 6-14% of cases.[3, 4, 7, 8] In one study the phenotype of ten cases with C-terminal deletions has been examined in detail,[9] but in no other study would they appear to have been specifically examined as a separate group. Using the data collected as part of InterRett, an international Rett syndrome phenotype database, and including data from the Australian Rett Syndrome Database, a population-based cohort, the phenotype of C-terminal deletions is described and compared with the phenotype of cases with all other mutations and also with recognised severe and mild mutations.