AUTHOR=Berry-Kravis Elizabeth , Filipink Robyn A. , Frye Richard E. , Golla Sailaja , Morris Stephanie M. , Andrews Howard , Choo Tse-Hwei , Kaufmann Walter E. , The FORWARD Consortium , Berry-Kravis Elizabeth , Velinov Milen , Talboy Amy L. , Sherman Stephanie L. , Kaufmann Walter E. , Schuster Marcy , Tartaglia Nicole , Filipink Robyn A. , Budimirovic Dejan B. , Barbouth Deborah , Lightbody Amy , Reiss Allan , Delahunty Carol M. , Hagerman Randi J. , Hessl David , Erickson Craig A. , Feldman Gary , Picker Jonathan D. , Lachiewicz Ave M. , Harris Holly K. , Esler Amy , Frye Richard E. , Evans Patricia A. , Morris Mary Ann , Haas-Givler Barbara A. , Gropman Andrea L. , Uy Ryan S. , Lozano Reymundo , Buchanan Carrie , Frazier Jean A. , Morris Stephanie M. TITLE=Seizures in Fragile X Syndrome: Associations and Longitudinal Analysis of a Large Clinic-Based Cohort JOURNAL=Frontiers in Pediatrics VOLUME=9 YEAR=2021 URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2021.736255 DOI=10.3389/fped.2021.736255 ISSN=2296-2360 ABSTRACT=

Fragile X syndrome (FXS), the most common inherited cause of intellectual disability, learning disability, and autism spectrum disorder, is associated with an increased prevalence of certain medical conditions including seizures. The goal of this study was to better understand seizures in individuals with FXS using the Fragile X Online Registry with Accessible Research Database, a multisite observational study initiated in 2012 involving FXS clinics in the Fragile X Clinic and Research Consortium. Seizure data were available for 1,607 participants, mostly male (77%) and white (74.5%). The overall prevalence of at least one seizure was 12%, with this rate being significantly higher in males than females (13.7 vs. 6.2%, p < 0.001). As compared to individuals with FXS without seizures, those with seizures were more likely to have autism spectrum disorder, current sleep apnea, later acquisition of expressive language, more severe intellectual disability, hyperactivity, irritability, and stereotyped movements. The mean age of seizure onset was 6.4 (SD 6.1) years of age with the great majority (>80%) having onset of seizures which was before 10. For those with epilepsy, about half (52%) had seizures for more than 3 years. This group was found to have greater cognitive and language impairment, but not behavioral disruptions, compared with those with seizures for <3 years. Antiepileptic drugs were more often used in males (60.6%) than females (34.8%), and females more often required more than one medication. The most commonly used anticonvulsants were oxcarbazepine, valproic acid, lamotrigine, and levetiracetam. The current study is the largest and first longitudinal study ever conducted to describe seizures in FXS. Overall, this study confirms previous reports of seizures in FXS and extends previous findings by further defining the cognitive and behavioral phenotype of those with epilepsy in FXS. Future studies should further investigate the natural history of seizures in FXS and the characteristics of seizures in FXS in adulthood.