Neurological and endocrine phenotypes of fragile X carrier women

Clin Genet. 2016 Jan;89(1):60-7. doi: 10.1111/cge.12646. Epub 2015 Sep 4.

Abstract

Women who carry fragile X mental retardation 1 (FMR1)gene premutation expansions frequently report neurological or endocrine symptoms and prior studies have predominantly focused on questionnaire report of medical issues. Premutation carrier (PMC) women (n = 33) and non-carrier controls (n = 13) were recruited and evaluated by a neurologist, neuropsychologist, and endocrinologist. Blood and skin biopsies were collected for molecular measures. Scales for movement disorders, neuropathy, cognitive function, psychiatric symptoms, sleep, and quality of life were completed. The average age of the women was 51 years (n = 46) and average CGG repeat size was 91 ± 24.9 in the FMR1 PMC women. Seventy percent of the PMC women had an abnormal neurological examination. PMC women had significantly higher scores on the Fragile X-Associated Tremor Ataxia Syndrome (FXTAS) rating scale, more neuropathy, and difficulty with tandem gait compared to controls. Central sensitivity syndromes, a neuroticism profile on the NEO Personality Profile, and sleep disorders were also prevalent. Discrepancies between subject report and examination findings were also seen. This pilot study suggests that women with the FMR1 premutation may have a phenotype that overlaps with that seen in FXTAS. Additional research with larger sample sizes is warranted to better delineate the clinical features.

Keywords: fragile X mental retardation 1 gene; fragile X syndrome; fragile X-associated tremor/ataxia syndrome; premutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Female
  • Fragile X Mental Retardation Protein / genetics
  • Fragile X Syndrome / diagnosis*
  • Fragile X Syndrome / genetics*
  • Fragile X Syndrome / physiopathology
  • Genetic Association Studies*
  • Heterozygote*
  • Humans
  • Middle Aged
  • Mutation
  • Neuropsychological Tests
  • Phenotype*
  • Trinucleotide Repeat Expansion

Substances

  • FMR1 protein, human
  • Fragile X Mental Retardation Protein