Trajectory of skill acquisition, loss, and regain in females with classic Rett syndrome

TL;DR

This study tracks how developmental skills are gained, lost, and regained in females with Classic Rett syndrome, focusing on age-related patterns and implications for clinical trials.

Contribution

The study provides detailed age-specific trajectories of skill acquisition, loss, and regain in Classic Rett syndrome, offering new insights for clinical trial design.

Findings

Skill acquisition peaks at age 6, with lower-level skills acquired more frequently than advanced skills.

Skill loss typically occurs within 2 years of acquisition, with minimal regain in fine motor, communication, and social skills after age 6.

Regain of skills generally stops by age 6, suggesting functional gains post-6 years are rare and significant for treatment evaluation.

Abstract

To characterize frequency, timing, and trajectory of gain, loss, and regain of developmental skills in Classic Rett syndrome (RTT).

The frequency and timing of gain, loss, and regain of 51 developmental skills from 1228 females with Classic RTT and a pathogenic loss-of-function variant in MECP2 was assessed during in-person visits from participants enrolled in the US Natural History Study. The percentage of participants experiencing gain, loss, or regain events, mean and median age of event and time to event with confidence intervals, and the cumulative incidence curves were calculated and compared to normative data using SPSS v29.0.2.0. One-year incidence of either gain or regain of each skill from 0–20 years old and one-year incidence of either gain or regain of any of 51 developmental skills was calculated.

The acquisition of skills was greatest for lower-level skills and conversely lowest for more advanced skills. Acquisition of skills peaked at 6 years. Skill loss occurred mainly within 2 years of acquisition. Loss of fine motor, communication, and social adaptive skills changed little after age 6 years. The regain of lost skills involved less than 30% of fine motor, communication, and social adaptation. Regain of skills generally ceased by age 6 years.

These results provide critical endpoints essential for conducting clinical trials in RTT. The lack of acquisition of skills beyond age 6 years and absence of loss or regain of previously lost skills, aside from gross motor features, beyond 6 years suggest that functional gains in these realms would represent important indicators of efficacy.

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