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JAMA Neurol. 2013 Mar 1;70(3):365-73. doi: 10.1001/2013.jamaneurol.181.

Distinct clinical characteristics of C9orf72 expansion carriers compared with GRN, MAPT, and nonmutation carriers in a Flanders-Belgian FTLD cohort.

Author information

1
VIB–Department of Molecular Genetics, Neurodegenerative Brain Diseases Group, University of Antwerp–CDE, Universiteitsplein 1, Antwerp, Belgium. christine.vanbroeckhoven@molgen.vib-ua.be

Abstract

OBJECTIVE:

To characterize patients with frontotemporal lobar degeneration (FTLD) with a repeat expansion mutation in the gene C9orf72, and to determine whether there are differences in the clinical presentation compared with FTLD carriers of a mutation in GRN or MAPT or with patients with FTLD without mutation.

DESIGN:

Patient series.

SETTING:

Dementia clinics in Flanders, Belgium.

PATIENTS:

Two hundred seventy-five genetically and phenotypically thoroughly characterized patients with FTLD.

MAIN OUTCOME MEASURES:

Clinical and demographic characteristics of 26 C9orf72 expansion carriers compared with patients with a GRN or MAPT mutation, as well as patients with familial and sporadic FTLD without mutation.

RESULTS:

C9orf72 expansion carriers developed FTLD at an early age (average, 55.3 years; range, 42-69 years), significantly earlier than in GRN mutation carriers or patients with FTLD without mutation. Mean survival (6.2 years; range, 1.5-17.0 years) was similar to other patient groups. Most developed behavioral variant frontotemporal dementia (85%), with disinhibited behavior as the prominent feature. Concomitant amyotrophic lateral sclerosis is a strong distinguishing feature for C9orf72 -associated FTLD. However, in most patients (73%), amyotrophic lateral sclerosis symptoms were absent. Compared with C9orf72 expansion carriers, nonfluent aphasia and limb apraxia were significantly more common in GRN mutation carriers.

CONCLUSIONS:

C9orf72 -associated FTLD most often presents with early-onset behavioral variant frontotemporal dementia with disinhibition as the prominent feature, with or without amyotrophic lateral sclerosis. Based on the observed genotype-phenotype correlations between the different FTLD syndromes and different genetic causes, we propose a decision tree to guide clinical genetic testing in patients clinically diagnosed as having FTLD.

PMID:
23338682
DOI:
10.1001/2013.jamaneurol.181
[Indexed for MEDLINE]
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