Title: Distinct Clinical Characteristics of C9orf72 Expansion Carriers Compared With GRN, MAPT, and Nonmutation Carriers in a Flanders-Belgian FTLD Cohort
Authors: Van Langenhove, Tim ×
van der Zee, Julie
Gijselinck, Ilse
Engelborghs, Sebastiaan
Vandenberghe, Rik
Vandenbulcke, Mathieu
de Bleecker, Jan
Sieben, Anne
Versijpt, Jan
Ivanoiu, Adrian
Deryck, Olivier
Willems, Christiana
Dillen, Lubina
Philtjens, Stéphanie
Maes, Githa
Bäumer, Veerle
Van Den Broeck, Marleen
Mattheijssens, Maria
Peeters, Karin
Martin, Jean-Jacques
Michotte, Alex
Santens, Patrick
De Jonghe, Peter
Cras, Patrick
De Deyn, Peter P
Cruts, Marc
Van Broeckhoven, Christine #
Issue Date: Mar-2013
Publisher: American Medical Association
Series Title: JAMA Neurology vol:70 issue:3 pages:365-373
Article number: 10.1001/2013.jamaneurol.181
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.
ISSN: 2168-6149
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Research Group Psychiatry
Medicine Teaching Programs
× corresponding author
# (joint) last author

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