title: Expanded clinical phenotype of women with the FMR1 premutation.
abstract: Fragile X-associated tremor/ataxia syndrome (FXTAS) is generally considered to be uncommon in older female carriers of premutation alleles (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene; however, neither prevalence, nor the nature of the clinical phenotype, has been well characterized in female carriers. In this study, we evaluated 146 female carriers (mean, 42.3 years; range, 20-75 years) with and without core features of FXTAS (tremor; gait ataxia), and 69 age-matched controls (mean, 45.8 years; range, 21-78 years). Compared with controls, carriers with definite or probable FXTAS had greater medical co-morbidity, with increased prevalence of thyroid disease (P = 0.0096), hypertension (P = 0.0020), seizures (P = 0.0077), peripheral neuropathy (P = 0.0040), and fibromyalgia (P = 0.0097), in addition to the typical symptoms of FXTAS-tremor (P < 0.0001) and ataxia (P < 0.0001). The non-FXTAS premutation group had more complaints of chronic muscle pain (P = 0.0097), persistent paraesthesias in extremities (P < 0.0001), and history of tremor (P < 0.0123) than controls. The spectrum of clinical involvement in female carriers with FXTAS is quite broad, encompassing a number of medical co-morbidities as well as the core movement disorder. The remarkable degree of thyroid dysfunction (17% in the non-FXTAS group and 50% in the FXTAS group) warrants consideration of thyroid function studies in all female premutation carriers, particularly those with core features of FXTAS.
authors.affiliation: Department of Pediatrics, University of California at Davis Medical Center, Sacramento, California 95817, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Coffey
authors.forename: Kylee
authors.initials: K
authors.lastname: Cook
authors.forename: Nicole
authors.initials: N
authors.lastname: Tartaglia
authors.forename: Flora
authors.initials: F
authors.lastname: Tassone
authors.forename: Danh V
authors.initials: DV
authors.lastname: Nguyen
authors.forename: Ruiqin
authors.initials: R
authors.lastname: Pan
authors.forename: Hannah E
authors.initials: HE
authors.lastname: Bronsky
authors.forename: Jennifer
authors.initials: J
authors.lastname: Yuhas
authors.forename: Mariya
authors.initials: M
authors.lastname: Borodyanskaya
authors.forename: Jim
authors.initials: J
authors.lastname: Grigsby
authors.forename: Melanie
authors.initials: M
authors.lastname: Doerflinger
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hagerman
authors.forename: Randi J
authors.initials: RJ
authors.lastname: Hagerman
mesh_terms: D000328:Adult; D000368:Aged; D001259:Ataxia / Q000235:genetics / Q000473:pathology; D042622:DNA Repeat Expansion; D005260:Female; D005356:Fibromyalgia / Q000473:pathology; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D006973:Hypertension / Q000473:pathology; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000473:pathology; D010641:Phenotype; D012640:Seizures / Q000473:pathology; D013959:Thyroid Diseases / Q000473:pathology; D014202:Tremor / Q000235:genetics / Q000473:pathology; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human