Fragile Females: Case Series of Epilepsy in Girls With <i>FMR1</i> Disruption.

Abstract

Girls with pathogenic variants in <i>FMR1</i>, the gene responsible for Fragile X syndrome, have received relatively little attention in the literature. The reports of girls with trinucleotide expansions or deletions affecting <i>FMR1</i> describe variable phenotypes; having normal intelligence and no severe neurologic sequelae is not uncommon. We reviewed epilepsy genetics research databases for girls with <i>FMR1</i> pathogenic variants and seizures to characterize the spectrum of epilepsy phenotypes. We identified 4 patients, 3 of whom had drug-resistant focal epilepsy. Two had severe developmental and epileptic encephalopathy with late-onset epileptic spasms. Our findings demonstrate that <i>FMR1</i> loss-of-function variants can result in severe neurologic phenotypes in girls. Similar cases may be missed because clinicians may not always perform Fragile X testing in girls, particularly those with severe neurodevelopmental impairment or late-onset spasms.