Language

English

Publication Date

8-22-2024

Journal

Genes

DOI

10.3390/genes15081107

PMID

39202466

PMCID

PMC11353339

PubMedCentral® Posted Date

8-22-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Although long-term survival in Rett syndrome (RTT) has been observed, limited information on older people with RTT exists. We hypothesized that increased longevity in RTT would be associated with genetic variants in MECP2 associated with milder severity, and that clinical features would not be static in older individuals. To address these hypotheses, we compared the distribution of MECP2 variants and clinical severity between younger individuals with Classic RTT (under 30 years old) and older individuals (over 30 years old). Contrary to expectation, enrichment of a severe MECP2 variant (R106W) was observed in the older cohort. Overall severity was not different between the cohorts, but specific clinical features varied between the cohorts. Overall severity from first to last visit increased in the younger cohort but not in the older cohort. While some specific clinical features in the older cohort were stable from the first to the last visit, others showed improvement or worsening. These data do not support the hypothesis that mild MECP2 variants or less overall severity leads to increased longevity in RTT but demonstrate that clinical features change with increasing age in adults with RTT. Additional work is needed to understand disease progression in adults with RTT.

Keywords

Rett Syndrome, Humans, Methyl-CpG-Binding Protein 2, Adult, Female, Disease Progression, Adolescent, Young Adult, Male, Middle Aged, Child, Child, Preschool, Aged, Longevity, Cohort Studies, Mutation, Rett syndrome, MECP2, old age, clinical severity, disease progression

Published Open-Access

yes

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