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22-02-2012 | Psychology | Article

ALS patients with genetic repeat expansion show similar recognizable characteristics


Free abstract

MedWire News: Specific clinical characteristics have been identified in patients with amyotrophic lateral sclerosis (ALS) who exhibit a repeat expansion sequence in the C9orf72 gene, according to research published in The Lancet Neurology.

The researchers found that the expansion was associated with earlier disease onset, cognitive and behavioral impairment, specific neuroimaging changes, a family history of neurodegeneration, and reduced survival, among ALS patients.

In an accompanying editorial Peter Andersen of Umeå University in Sweden writes: "Byrne and colleagues' findings substantially increase our knowledge about families with the C9orf72 repeat expansion but I concur with the investigators that predictive testing in these families is premature.

"Unfortunately, the high prevalence of this repeat expansion might tempt DNA diagnostic laboratories to offer this test soon."

ALS is a progressive neurodegenerative disease associated with cognitive impairment in up to half of cases, and frontotemporal dementia (FTD) in every one in seven.

In this study, Susan Byrne (Trinity College, Dublin, Ireland) and colleagues studied DNA bank samples from 49 patients with known familial ALS and 386 apparently sporadic cases. They found that 41% of the familial ALS cases and 5% of the apparently sporadic cases had the GGGGCC repeat expansion in C9orf72.

The research team analyzed phenotype data for 191 patients, 11% of whom had the repeat expansion.

They found that the mean age of disease onset was 56.3 years in the patients with the repeat expansion, which was significantly lower than the 61.3 years seen in the patients without the expansion.

A family history of ALS or FTD was found in 86% of patients with the repeat expansion, whereas a family history of FTD was found in only 2% of the patients without the expansion. The patients with the repeat expansion also had a significantly higher incidence of co-morbid FTD than those without (50 vs 12%), and shorter survival (20 vs 26 months).

In addition, the researchers conducted 3 T magnetic resonance gray-matter voxel-based morphometry in 10 patients with the repeat expansion and 30 age- and disease-matched controls. They found significant differences in the right inferior frontal gyrus, right superior frontal gyrus, left anterior cingulated gyrus, and the right precentral gyrus.

"Other consequences of the study might be that the Awaji-El Escorial diagnostic criteria for ALS need to be revised to incorporate tests for cognitive and behavioural impairment, and the definition of familial ALS should include the presence of a family history of other neurodegenerative diseases, especially FTD," suggests Anderson.

By Chloe McIvor

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