Background: Rett syndrome (RTT) is a genetic-related neurodevelopmental disorder that usually affects females. In Taiwan, there is lack of information in terms of the genetic mutations and clinical characteristics of RTT. Therefore, our aim is to describe the clinical features and delineate the genotype-phenotype correlation of RTT in Taiwan.

Method: In this nation-wide cross-sectional study, a database registry of RTT, covering both clinical characteristics and genetic mutations, was setup for registry. We recruited all individuals diagnosed with RTT in Taiwan.

Results: A total of 72 cases of typical RTT and 17 cases of atypical RTT, aged from 1.9 to 39.9 years, were enrolled. The majority (66.3%) was in moderate clinical severities, while 14.6% and 19.1 % were associated with mild and severe clinical severities. The hand function, gait and language function were significantly regressed in typical RTT. The mean age of onset of regression was 1.1 ±0.8 years for hand function, 2 ±1.6 years for language, and 3.6 ±4 years for ambulation. Total 70.8% did not have language function, 43.9% retained some hand functions, and 56.1% do not have independent gait. Regarding genetic mutation, 79% had MECP2 mutation, 5% had CDKL5 mutation, while 3% had FOXG1 mutation. Certain genotypes (p.R294X, and C-terminal mutations) were associated with milder phenotype, while R168X was associated with severe phenotype.

Conclusion: We described the clinical characteristics and genotype-phenotype correlations of RTT in Taiwan. The much variability of genotype-phenotype correlation found in our cohort may reflect the distinctive clinical entities in our cohort.