Date of Award

Spring 2021

Document Type

Open Access Thesis

Department

Genetic Counseling

First Advisor

Debera Zvejnieks

Abstract

Rett syndrome (RTT) is a neurodevelopmental disorder impacting 1 in 10,000 females worldwide, making it one of the most common causes of complex disability in girls. RTT is caused by pathogenic variants in the MECP2 gene and is characterized by developmental regression, stereotypical hand movements, and an abnormal gait. Despite consistency in the presence of these core features, a wide range of features and varying severity can be observed in girls with RTT. Similarly, the particular type of MECP2 variant present also differs between patients. Previous studies have assessed correlations between genotype and phenotype in patients with RTT. While past research revealed some correlations, they were limited by small sample size and inconsistencies in data collection methods. This study uses data from the Rett Syndrome Natural History Study (RSNHS), a nationwide study that has been enrolling patients for the past 15 years. The analysis focuses on further characterizing developmental regression and features present in patients with RTT. The study also elucidates genotype-phenotype correlations in RTT, including patients with less common variants in MECP2. Analysis of these correlations focuses not only on overall severity but also on details of development and the presence of particular features. Results are consistent with previous studies of genotype-phenotype correlations in RTT and suggest that multiple features of RTT, including overall severity, regression onset, motor skills, and head circumference, differ significantly based on the type of MECP2 variant present. These correlations could provide important prognostic information for families with a new diagnosis of RTT.

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