UC Davis

It is now recognized that FMR1 premutation carriers (PC) are at risk to develop a range of neurological, psychiatric, and immune-mediated disorders during adulthood. There are conflicting findings regarding the incidence of hypertension, hypothyroidism, diabetes, and cancer in these patients that warrant further study. A retrospective controlled study was performed in a convenience sample of 248 controls (130 men, 118 women) and 397 FMR1 PC with and without fragile X-associated tremor ataxia syndrome (FXTAS) (176 men, 221 women); all participants were at least 45 years old (men: mean 62.4, SD 9.5; women: mean 62.8, SD 9.9; p = 0.63). Memory and cognitive assessments (Wechsler Adult Intelligence Scale (WAIS-III), Wechsler Memory Scale (WMS-III)) and molecular testing (CGG repeats and FMR1-mRNA levels) were performed. Additional data included body mass index (BMI), cholesterol levels, blood pressure, hemoglobin A1c (HbA1c) levels, and medical history. A higher percentage of PC subjects self-reported having a diagnosis of hypertension (50.0 vs. 35.0 %, p = 0.006) and thyroid problems (20.4 vs. 10.0 %, p = 0.012) than control subjects. When comparing controls versus PC with FXTAS, the association was higher for diabetes (p = 0.043); however, the effect was not significant after adjusting for demographic predictors. Blood pressure, blood glucose levels, HbA1c, and BMI values were not significantly different between the two groups. The PC with FXTAS group performed consistently lower in neuropsychological testing compared with the PC without FXTAS group, but the differences were very small for all but the WAIS full-scale IQ. Based on these findings, it appears that the risk for hypertension, thyroid problems, and diabetes may be more frequent in PC with FXTAS, which will require verification in future studies.