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Abstracts

Clinical Signature and Longitudinal Seizure Pattern of SLC6A1-Related Neurodevelopmental Disorder

Abstract number : 2.059
Submission category : 12. Genetics / 12A. Human Studies
Year : 2025
Submission ID : 1222
Source : www.aesnet.org
Presentation date : 12/7/2025 12:00:00 AM
Published date :

Authors :
Presenting Author: Laina Lusk, MMSc, CGC – Children's Hospital of Philadelphia

Samuel Miller, MS – University of Pennsylvania
Pamela Pojomovsky McDonnell, MD – Children's Hospital of Philadelphia
Michael Kaufman, MS – Children's Hospital of Philadelphia
Jillian McKee, MD, PhD – Children's Hospital of Philadelphia & University of Pennsylvania
Ingo Helbig, MD – Children's Hospital of Philadelphia

Rationale: SLC6A1-related Neurodevelopmental Disorder (NDD) is characterized by mild to severe developmental delays and/or intellectual disability, early onset epilepsy, hypotonia, and neurobehavioral manifestations that can include autism spectrum disorder, psychiatric disorders, and behavioral problems. Movement disorders and gastrointestinal symptoms may occur as well. While seizure onset and types are documented, data on natural history, medication response, and long-term prognosis are limited.

Methods: Retrospective chart review was performed on patients seen at the Children’s Hospital of Philadelphia. Data collection included genetic diagnosis, all documented diagnoses (particularly neurological diagnoses), and developmental milestones. Seizure types and frequencies as well as anti-seizure medication (ASM) types were recorded for each month of life. Phenotypic traits were also recorded and standardized using the Human Phenotype Ontology (HPO).

Results: Our cohort included 33 individuals (17 female), with an age range of 3-37 years at the time of data collection, and a total of 3476 patient-months (289.7 patient-years). Gross and fine motor milestones were achieved on time by 64% (21/33) and 61% (20/33), respectively. Only 6% (2/33) reached language milestones on time. 67% (22/33) of the individuals had seizures, with the most common types being atypical absence (77%, 17/22), myoclonic atonic (27%, 6/22), atonic (18%, 4/22), and typical absence (14%, 3/22). Median age of onset was 29 months (range: 6-89 months). 55% (12/22) achieved at least 24 months of seizure freedom at a median seizure offset of 7.4 years (range 4-12 years). Among the 5 adults with epilepsy history data, 60% (3/5) were seizure free with or without ASM. The overall pattern of seizures involved onset around 1 year of age (with some diagnosed in infancy), peak of seizures around 3 years of age, and gradual tapering of seizures in later years. The most common ASMs used were valproic acid (59%, 13/22), levetiracetam (59%, 13/22), lamotrigine (50%, 11/22), ethosuximide (45%, 10/22), and clobazam (41%, 9/22). Valproic acid (VPA) and clobazam (CLB) were significantly associated with maintenance of seizure freedom (ORs: VPA = 3.0, CLB = 3.3) and either a decrease in seizures or maintenance of seizure freedom (ORs: VPA = 1.3, CLB 1.4) in our cohort (p < 0.001).
Genetics