Longitudinal characterization of clinical and developmental trajectories in MECP2 duplication syndrome
Abstract number :
2.061
Submission category :
12. Genetics / 12A. Human Studies
Year :
2025
Submission ID :
575
Source :
www.aesnet.org
Presentation date :
12/7/2025 12:00:00 AM
Published date :
Authors :
Presenting Author: Kelsey Frahlich, RN, BSN – Citizen Health
Elizabeth Blomenberg, PA, MSHS – Citizen Health
Mariah Crabtree, AuD – Citizen Health
Ashley Mabry, APRN, CPNP-AC – Citizen Health
Emily McNaughton, MPH – Citizen Health
Elise Brimble, MSc, MS, CGC – Citizen Health
Rationale: MECP2 duplication syndrome (MDS) is a rare neurodevelopmental disorder characterized by developmental and intellectual disabilities (DD/ID), infantile hypotonia, recurrent infections, and epilepsy. With the advent of precision therapies, establishing natural history is critical for clinical trial readiness. However, these studies are challenging to conduct in small, distributed populations. In this study, we use real-world data (RWD) to characterize developmental and epilepsy trajectories in a large MDS sample population, and explore their contributions to overall disease burden.
Methods: Participants were enrolled in Citizen Health, a patient-centric RWD platform that collects and structures electronic health records. Records were reviewed for relevant variables and fit to a data model encompassing 18 clinical entities, including genetic test results, clinical and developmental phenotypes, and interventions. Data were harmonized through the use of standard terminologies. Technical and operational protocols were employed to ensure data completeness, conformance with data standards, and fidelity. Descriptive and inferential statistics were used in this retrospective observational study.
Results: The study population included 50 individuals (n=45 male) with (likely) pathogenic copy number gains involving MECP2, for whom a total of 22,967 variables were annotated. Median age of study participants was 6.3 years (range 1.1-22.3) with a median duration of follow-up of 6.0 years (range 0.9-21.9). Median duplication size was ~600 kb (range 242 kb-15.4 Mb) and encompassed a median of 110.5 genes (range 14-674). All participants had DD/ID, hypotonia, and feeding problems. Epilepsy was documented in n=23 (46%) with a median age of onset of 5.5 years (range 0.5-12.8). Individuals with epilepsy were older [median age 8.9 years (range 0.9-21.9) vs 4.5 years (range 1.3-12.6, P< 0.01], and had higher frequencies of hypertonia (74% vs 37%,
Genetics