• Tim Van Langenhove, Julie van der Zee, Ilse Gijselinck, Sebastiaan Engelborghs, Rik Vandenberghe, Mathieu Vandenbulcke, Jan De Bleecker, Anne Sieben, Jan Versijpt, Adrian Ivanoiu, Olivier Deryck, Christiana Willems, Lubina Dillen, Stéphanie Philtjens, Githa Maes, Veerle Bäumer, Marleen Van Den Broeck, Maria Mattheijssens, Karin Peeters, Jean-Jacques Martin, Alex Michotte, Patrick Santens, Peter De Jonghe, Patrick Cras, Peter P De Deyn, Marc Cruts, and Christine Van Broeckhoven.
• VIB–Department of Molecular Genetics, Neurodegenerative Brain Diseases Group, University of Antwerp–CDE, Universiteitsplein 1, Antwerp, Belgium. christine.vanbroeckhoven@molgen.vib-ua.be
• JAMA Neurol. 2013 Mar 1; 70 (3): 365-73.

ObjectiveTo 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.DesignPatient series.SettingDementia clinics in Flanders, Belgium.PatientsTwo hundred seventy-five genetically and phenotypically thoroughly characterized patients with FTLD.Main Outcome MeasuresClinical 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.ResultsC9orf72 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.ConclusionsC9orf72 -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.

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