Parkinsonism in FMR1 premutation carriers may be indistinguishable from Parkinson disease

Abstract

Premutation carriers of repeat expansions in the fragile X mental retardation (FMR1) gene develop kinetic tremor and ataxia or the 'fragile X associated tremor/ataxia syndrome' (FXTAS). Affected FMR1 premutation carriers also have parkinsonism, but have not been reported to meet criteria for Parkinson disease. This case series illustrates that some patients who are FMR1 premutation carriers may appear by history and examination to have idiopathic Parkinson disease. Based on previous studies, it is likely that the genetic mutation and parkinsonism are associated. Although screening all PD patients is likely to be low yield, genetic testing of FMR1 in individuals with PD and a family history of fragile X syndrome, autism or developmental delay, or other related FMR1 phenotypes is warranted.

Figures

Fig. 1

(A) Pedigree of Case 2. (B) Pedigree of Case 3. (C) Pedigree of Case 4. FMR1 premutation carrier; ■ FMR1 full mutation; FMR1 premutation carrier with Parkinson disease; Parkinson disease; ◇ Unknown gender.