Fragile Females: Case Series of Epilepsy in Girls With FMR1 Disruption

Pediatrics. 2019 Sep;144(3):e20190599. doi: 10.1542/peds.2019-0599. Epub 2019 Aug 22.

Abstract

Girls with pathogenic variants in FMR1, 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 FMR1 describe variable phenotypes; having normal intelligence and no severe neurologic sequelae is not uncommon. We reviewed epilepsy genetics research databases for girls with FMR1 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 FMR1 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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Brain Diseases / genetics
  • Child
  • Child, Preschool
  • Drug Resistant Epilepsy / genetics*
  • Female
  • Fragile X Mental Retardation Protein / genetics*
  • Fragile X Syndrome / genetics*
  • Humans
  • Intellectual Disability / genetics*
  • Loss of Function Mutation*
  • Retrospective Studies

Substances

  • FMR1 protein, human
  • Fragile X Mental Retardation Protein