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  • Case Study
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Fragile X-associated tremor/ataxia syndrome—an older face of the fragile X gene


Background A 76-year-old man presented with an 8-year history of balance problems and a 2-year history of short-term memory loss. He had also been experiencing long-term problems with impotence and episodes of urinary incontinence, and had been managed for hypertension for 25 years. His medical history was otherwise unremarkable. Three of his grandchildren had been diagnosed with fragile X syndrome.

Investigations Neurological examination, cognitive and neuropsychological testing, nerve conduction studies, MRI, and genetic testing.

Diagnosis Fragile X-associated tremor/ataxia syndrome (FXTAS) resulting from a premutation (CGG repeat) expansion of the FMR1 gene.

Management Explanation of the genetic ramifications of premutation carrier status for the FMR1 gene, and symptomatic treatment for the clinical difficulties experienced by the patient.

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Figure 1: MRI of the patient at the age of 72 years.
Figure 2: Clinical and pathogenic consequences of expanded CGG repeats in the FMR1 gene.
Figure 3: Ubiquitin-positive intranuclear inclusions (black arrowhead) within a centrally located neuronal cell body and two adjacent astroglial nuclei from a patient who died with fragile X-associated tremor/ataxia syndrome.


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The authors wish to thank Dr J Brunberg and Dr C Greco for their contributions of MRI and inclusion images, respectively, and Dr R Maselli and G Fenton-Farrell for their input into the nerve conduction studies. This work was supported by the NINDS (NS43532; PJH), the NIA (AG024488; PJH), the NICHD (HD36071 and HD02274; RJH), and the CDC (U1O/CCU 92513; RJH).

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Correspondence to Paul J Hagerman.

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Hagerman, P., Hagerman, R. Fragile X-associated tremor/ataxia syndrome—an older face of the fragile X gene. Nat Rev Neurol 3, 107–112 (2007).

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