TY - JOUR
T1 - Distinct Clinical Characteristics of C9orf72 Expansion Carriers Compared With GRN, MAPT, and Nonmutation Carriers in a Flanders-Belgian FTLD Cohort
AU - Van Langenhove, Tim
AU - van der Zee, Julie
AU - Gijselinck, Ilse
AU - Engelborghs, Sebastiaan
AU - Vandenberghe, Rik
AU - Vandenbulcke, Mathieu
AU - De Bleecker, Jan
AU - Sieben, Anne
AU - Versijpt, Jan
AU - Ivanoiu, Adrian
AU - Deryck, Olivier
AU - Willems, Christiana
AU - Dillen, Lubina
AU - Philtjens, Stephanie
AU - Maes, Githa
AU - Baumer, Veerle
AU - Van den Broeck, Marleen
AU - Mattheijssens, Maria
AU - Peeters, Karin
AU - Martin, Jean-Jacques
AU - Michotte, Alex
AU - Santens, Patrick
AU - De Jonghe, Peter
AU - Cras, Patrick
AU - De Deyn, Peter P.
AU - Cruts, Marc
AU - Van Broeckhoven, Christine
PY - 2013/3
Y1 - 2013/3
N2 - 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. JAMA Neurol. 2013;70(3):365-373. Published online January 21, 2013. doi:10.1001/2013.jamaneurol.181
AB - 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. JAMA Neurol. 2013;70(3):365-373. Published online January 21, 2013. doi:10.1001/2013.jamaneurol.181
KW - AMYOTROPHIC-LATERAL-SCLEROSIS
KW - FRONTOTEMPORAL LOBAR DEGENERATION
KW - HEXANUCLEOTIDE REPEAT EXPANSION
KW - PROGRESSIVE SUPRANUCLEAR PALSY
KW - CORTICOBASAL DEGENERATION
KW - PATHOLOGICAL FEATURES
KW - DIAGNOSTIC-CRITERIA
KW - CHROMOSOME 9P
KW - DEMENTIA
KW - MUTATION
U2 - 10.1001/2013.jamaneurol.181
DO - 10.1001/2013.jamaneurol.181
M3 - Article
SN - 2168-6149
VL - 70
SP - 365
EP - 373
JO - Jama neurology
JF - Jama neurology
IS - 3
ER -