Behavioral Variant Frontotemporal Dementia With C9orf72 Intermediate Repeat Expansion

Hexanucleotide repeat expansion in the chromosome 9 open reading frame 72 ( C9orf72 ) gene has been identified as the most common genetic cause of both frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). While large pathogenic expansions can reach hundreds to thousands of repeats, the lower limit for the number of pathogenic repeats remains controversial. Pathogenic threshold ranges from 30 to >60 repeats. Here, we report a rare case of behavioral variant frontotemporal dementia (bvFTD) associated with a C9orf72 repeat expansion of 49 units, a size that falls within the intermediate-length range. The patient presented with progressive neuropsychiatric decline, which progressed to include emotional blunting and memory impairment. Neuroimaging demonstrated bilateral temporal and hippocampal atrophy, with a reduction in glucose metabolism observed in the left fronto-parieto-temporal cortex and thalamus. This study may provide crucial clinical evidence for the ongoing debate on the pathogenicity of intermediate-length alleles in C9orf72 .