Progressieve ataxie en cognitieve achteruitgang door een premutatie in het fragiele-X-mentale-retardatiegen

A 75-year-old man had progressive difficulty with walking, intention tremor, ataxia, and mild cognitive deficits. MRI scan of the brain showed symmetrical hyperintensities in the middle cerebellar peduncles. DNA analysis of the fragile-X gene revealed an expansion of 150-200 repetitions in the FMR1-gene, compatible with a premutation in the fragile-X gene. Two years later, after progression of the symptoms, the patient was admitted to a nursing home. The clinical picture of intention tremor, parkinsonism and ataxia with white matter lesions and atrophy on MRI occurs in carriers of this premutation and has recently been described as the fragile-X-associated tremor/ataxia syndrome. Recognition of this clinical picture is important for the patient but also for the relatives, since female carriers of the premutation have an increased risk of offspring with the fragile-X syndrome.