Fragile X‐associated tremor/ataxia syndrome: Intrafamilial variability and the size of the <i>FMR1</i> premutation CGG repeat

Abstract

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurological progressive disorder associated with the FMR1 gene premutation. We report on variable presentation of findings associated with FXTAS in 3 brothers aged 68, 74, and 73 years, carrying premutation alleles of (CGG)(123,) (CGG)(109), and (CGG)(91) triplets, respectively. Based on previously proposed diagnostic criteria for the syndrome, clinical and radiological data allowed establishing a "definite" diagnosis of FXTAS in the two carriers of the longest (CGG)(n). The carrier of the (CGG)(91) allele, although presenting a major radiological sign of the syndrome (symmetrical white-matter lesions in the middle cerebellar peduncles), did not have any significant neurological manifestation at 73 years of age.