Characterization of a family with c9FTD/ALS associated with the GGGGCC repeat expansion in C9ORF72

Background: The hexanucleotide repeat in the chromosome 9 open reading frame 72 (C9ORF72) gene was recently discovered as the underlying genetic cause of many families with frontotemporal dementia (FTD) and/or amyotrophic lateral sclerosis (ALS) linked to chromosome 9 (c9FTD/ALS). We report the clinical, neuropsychologic, and neuroimaging findings of a family with the C9ORF72 mutation and clinical diagnoses bridging the FTD, parkinsonism, and ALS spectrum. Objective: To characterize the antemortem characteristics of a family with c9FTD/ALS associated with the GGGGCC repeat expansion in C9ORF72. Design: Clinical series. Setting: Tertiary care academic medical center. Patients: The members of a family affected by the mutation with features of FTD and/or ALS. Main Outcome Measures: Clinical, neuropsychologic, and neuroimaging assessments. Results: All 3 examined subjects had the hexanucleotide expansion detected in C9ORF72. All had personality/behavioral changes early in the course of the disease. One case had levodopa-unresponsive parkinsonism, and 1 had ALS. Magnetic resonance imaging showed symmetric bilateral frontal, temporal, insular, and cingulate atrophy. Conclusions: This report highlights the clinical and neuroimaging characteristics of a family with c9FTD/ALS. Further studies are needed to better understand the phenotypical variability and the cliniconeuroimaging-neuropathologic correlations.