AI Article Synopsis
- The study investigates neurodevelopmental disorders caused by pathogenic variants, focusing on individuals without epilepsy, as little is known about their development and potential treatment endpoints beyond seizure control.
- Researchers conducted a retrospective study collecting data from 71 individuals, including 44 new cases, assessing their medical histories and developmental outcomes using standardized measures.
- Findings revealed that 25% of the participants did not have epilepsy, and those without it generally had better motor function and developmental outcomes, suggesting distinct clinical features between individuals with and without a history of seizures.
Article Abstract
Background And Objectives: Pathogenic variants in are among the major genetic causes of neurodevelopmental disorders. Despite the increasing number of individuals diagnosed without a history of epilepsy, little is known about the natural history and developmental trajectories in this subgroup and endpoints for future therapeutic studies are limited to seizure control.
Methods: We performed a cross-sectional retrospective study using standardized questionnaires for clinicians and caregivers of individuals with -related disorders capturing medical histories, genetic findings, and developmental outcomes. Motor and language function were assessed using Gross Motor Function Classification System (GMFCS) scores and a speech impairment score and were compared within and across clinically defined subgroups.
Results: We collected data of 71 individuals with -related disorders, including 44 previously unreported individuals. Median age at inclusion was 5.3 years (interquartile range 3.5-9.3) with the oldest individual aged 43.8 years. Epilepsy was absent in 18/71 (25%) of individuals. The range of developmental outcomes was broad, including 2 individuals presenting with close to age-appropriate motor development. Twenty-nine of 61 individuals (48%) were able to walk unassisted, and 24/69 (35%) were able to speak single words. Individuals without epilepsy presented with a similar onset and spectrum of phenotypic features but had lower GMFCS scores (median 3 vs 4, < 0.01) than individuals with epilepsy. Individuals with epileptic spasms were less likely to walk unassisted than individuals with other seizure types (6% vs 58%, < 0.01). Individuals with early epilepsy onset had higher speech impairment scores ( = 0.02) than individuals with later epilepsy onset.
Discussion: We expand the spectrum of -related disorders and provide clinical features and developmental trajectories in individuals with and without a history of epilepsy. Individuals with epilepsy, in particular epileptic spasms, and neonatal or early-onset presented with less favorable motor and language functional outcomes compared with individuals without epilepsy. These findings identify children at risk for severe disease and can serve as comparator for future interventional studies in -related disorders.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10501093 | PMC |
| http://dx.doi.org/10.1212/WNL.0000000000207550 | DOI Listing |
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