Multiple System Atrophy and Amyotrophic Lateral Sclerosis in a Family With Hexanucleotide Repeat Expansions in C9orf72
ABSTRACT IMPORTANCE Here we report a family with coexistence of multiple system atrophy (MSA) and amyotrophic lateral sclerosis (ALS) with hexanucleotide repeat expansions in C9orf72. OBSERVATIONS A 65-year-old woman had a 2-year history of ataxia with autonomic dysfunction but without motor neuron signs. She was diagnosed as having MSA based on her clinical history and the hot cross bun sign on brain magnetic resonance imaging. Her 62-year-old brother had progressive weakness, fasciculations, hyperreflexia, and active denervation on electromyography without cerebellar ataxia. He was diagnosed as having ALS. Both patients had a greater than 1000/2 hexanucleotide expansion in C9orf72. CONCLUSIONS AND RELEVANCE Patients with hexanucleotide repeat expansions in C9orf72 can present with MSA as well as ALS or frontotemporal dementia. We report this family with coexisting MSA and ALS, highlighting the phenotypic variability in neurologic presentations with hexanucleotide repeat expansions in C9orf72.
- Journal of the Neurological Sciences 07/2014; 345(1-2). DOI:10.1016/j.jns.2014.07.027 · 2.26 Impact Factor
- JAMA Neurology 09/2014; 71(9):1191-2. DOI:10.1001/jamaneurol.2014.1811 · 7.01 Impact Factor
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ABSTRACT: Multiple system atrophy (MSA) is a fatal neurodegenerative disorder of unknown etiology that presents with variable combinations of progressive ataxia, parkinsonism and autonomic instability. Pathologic expansion of a hexanucleotide repeat in the gene C9orf72 gene has been demonstrated to cause neurodegeneration with diverse neurological presentations. To test the hypothesis whether pathologic expansions in C9orf72 are a cause of MSA, we undertook genetic screening in 100 neuropathologically confirmed cases. No pathologic repeat expansions were detected suggesting that MSA is not a C9orf72-related neurodegenerative disease.Neurobiology of Aging 09/2014; 36(2). DOI:10.1016/j.neurobiolaging.2014.08.033 · 4.85 Impact Factor