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.