biostudies-literatureNeul JLNICHD NIH HHSNCATS NIH HHSNational Institutes of HealthNIAMS NIH HHS228-238https://www.ebi.ac.uk/biostudies/studies/S-EPMC10939125biostudies-literatureUnknown1(3)<h4>Objective</h4>To determine the longitudinal distribution of hand function skills in individuals with classic Rett Syndrome (RTT), an X-linked dominant neurodevelopmental disorder, and correlate with <i>MECP2</i> variants.<h4>Method</h4>We conducted a longitudinal study of 946 girls and young women with typical RTT seen between 2006 and 2021 in the US Natural History Study (NHS) featuring a structured clinical evaluation to assess the level of hand function skills. The specific focus in this study was to assess longitudinal variation of hand skills from age 2 through age 18 years in relation to specific <i>MECP2</i> variant groups.<h4>Results</h4>Following the initial regression period, hand function continues to decline across the age spectrum in individuals with RTT. Specific differences are noted with steeper declines in hand function among those with milder variants (Group A: R133C, R294X, R306C, and C-terminal truncations) compared to groups composed of individuals with more severe variants.<h4>Conclusions</h4>These temporal variations in hand use represent specific considerations which could influence the design of clinical trials that test therapies aiming to ameliorate specific functional limitations in individuals with RTT. Furthermore, the distinct impact of specific <i>MECP2</i> variants on clinical severity, especially related to hand use, should be considered in such interventional trials.Annals of the Child Neurology SocietyDistribution of hand function by age in individuals with Rett syndrome.PMC10939125UL1 TR002243U54 HD083211P30 AR072583P50 HD103537HD083181U54HD083211UL1 TR000445U54 HD061222R01 HD083181Benke TARyther RCCBeisang AALieberman DNEdwards LJAnanth AMarsh EDLane JBPercy AKHeydemann PTNeul JLHaas RHSkinner SAStandridge SMGlaze DGSuter BfalseDistribution of hand function by age in individuals with Rett syndrome.<h4>Objective</h4>To determine the longitudinal distribution of hand function skills in individuals with classic Rett Syndrome (RTT), an X-linked dominant neurodevelopmental disorder, and correlate with <i>MECP2</i> variants.<h4>Method</h4>We conducted a longitudinal study of 946 girls and young women with typical RTT seen between 2006 and 2021 in the US Natural History Study (NHS) featuring a structured clinical evaluation to assess the level of hand function skills. The specific focus in this study was to assess longitudinal variation of hand skills from age 2 through age 18 years in relation to specific <i>MECP2</i> variant groups.<h4>Results</h4>Following the initial regression period, hand function continues to decline across the age spectrum in individuals with RTT. Specific differences are noted with steeper declines in hand function among those with milder variants (Group A: R133C, R294X, R306C, and C-terminal truncations) compared to groups composed of individuals with more severe variants.<h4>Conclusions</h4>These temporal variations in hand use represent specific considerations which could influence the design of clinical trials that test therapies aiming to ameliorate specific functional limitations in individuals with RTT. Furthermore, the distinct impact of specific <i>MECP2</i> variants on clinical severity, especially related to hand use, should be considered in such interventional trials.2023-01-01T00:00:00Z2023 Sep2026-06-03T00:16:31.507Z2025-04-06T19:31:02.898ZS-EPMC109391253849682510.1002/cns3.20038