Files and links (1)
Accepted (AM)Open Access (License Unspecified), Open
Journal article
Boricua Founder Variant inFRRS1LCauses Epileptic Encephalopathy With Hyperkinetic Movements
Journal of child neurology, v 36(2), pp 93-98
01 Feb 2021
PMID: 32928027
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Objective: To describe a founder mutation effect and the clinical phenotype of homozygousFRRS1Lc.737_739delGAG (p.Gly246del) variant in 15 children of Puerto Rican (Boricua) ancestry presenting with early infantile epileptic encephalopathy (EIEE-37) with prominent movement disorder. Background: EIEE-37 is caused by biallelic loss of function variants in theFRRS1Lgene, which is critical for AMPA-receptor function, resulting in intractable epilepsy and dyskinesia. Methods: A retrospective, multicenter chart review of patients sharing the same homozygousFRRS1L(p.Gly246del) pathogenic variant identified by clinical genetic testing. Clinical information was collected regarding neurodevelopmental outcomes, neuroimaging, electrographic features and clinical response to antiseizure medications. Results: Fifteen patients from 12 different families of Puerto Rican ancestry were homozygous for theFRRS1L(p.Gly246del) pathogenic variant, with ages ranging from 1 to 25 years. The onset of seizures was from 6 to 24 months. All had hypotonia, severe global developmental delay, and most had hyperkinetic involuntary movements. Developmental regression during the first year of life was common (86%). Electroencephalogram showed hypsarrhythmia in 66% (10/15), with many older children evolving into Lennox-Gastaut syndrome. Six patients demonstrated progressive volume loss and/or cerebellar atrophy on brain magnetic resonance imaging (MRI). Conclusions: We describe the largest cohort to date of patients with epileptic encephalopathy. We estimate that 0.76% of unaffected individuals of Puerto Rican ancestry carry this pathogenic variant due to a founder effect. Children homozygous for theFRRS1L(p.Gly246del) Boricua variant exhibit a very homogenous phenotype of early developmental regression and epilepsy, starting with infantile spasms and evolving into Lennox-Gastaut syndrome with hyperkinetic movement disorder.
Metrics
Details
- Title
- Boricua Founder Variant inFRRS1LCauses Epileptic Encephalopathy With Hyperkinetic Movements
- Creators
- Imane Abdelmoumen - St. Christopher's Hospital for ChildrenSandra Jimenez - St. Christopher's Hospital for ChildrenIgnacio Valencia - St. Christopher's Hospital for ChildrenJoseph Melvin - St. Christopher's Hospital for ChildrenAgustin Legido - St. Christopher's Hospital for ChildrenMayela M. Diaz-Diaz - University of Puerto Rico, Medical Sciences CampusChristopher Griffith - University of South FloridaLauren J. Massingham - Rhode Island HospitalMelissa Yelton - Boston Children's HospitalJanice Rodriguez-Hernandez - University of Puerto Rico, Medical Sciences CampusRhonda E. Schnur - Rowan UniversityLaurence E. Walsh - Indiana UniversityAna G. Cristancho - Children's Hospital of PhiladelphiaChristina A. Bergqvist - University of PennsylvaniaKirsty McWalter - GeneDxIain Mathieson - University of PennsylvaniaGillian M. Belbin - Institute for Genomic Health, 5925Icahn School of Medicine at Mount Sinai, New York, NY, USA.Eimear E. Kenny - Institute for Genomic Health, 5925Icahn School of Medicine at Mount Sinai, New York, NY, USA.Xilma R. Ortiz-Gonzalez - University of PennsylvaniaMichael C. Schneider - St. Christopher's Hospital for Children
- Publication Details
- Journal of child neurology, v 36(2), pp 93-98
- Publisher
- Sage
- Number of pages
- 6
- Grant note
- Robert Wood Johnson Foundation Harold Amos Faculty Development Award; Robert Wood Johnson Foundation (RWJF)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Web of Science ID
- WOS:000571234600001
- Scopus ID
- 2-s2.0-85091021464
- Other Identifier
- 991019169101104721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Clinical Neurology
- Pediatrics