Chromosome 9 open reading frame 72 (C9orf72) gene pathogenic variants have been typically associated with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), but recent studies suggest their involvement in other disorders. This report describes a family with an autosomal dominant pattern of inheritance of progressive verbal auditory agnosia due to GGGGCC repeat expansion in C9orf72. A 60-year-old right-handed male truck driver presented with slowly progressive poor speech perception for 8 years, which became most troublesome when receiving verbal orders over the phone. He had difficulty recognizing single-syllable spoken words beyond his hearing loss but had no problem understanding complex written language. He had a heterozygous pathogenic variant carrying 160 hexanucleotide repeats in the C9orf72 gene. His family history included his deceased mother with similar symptoms that had progressed over 30 years, as well as his older brother and youngest sister who experienced speech perception difficulty beginning in their early fifties. His asymptomatic younger brother had a heterozygous 2 repeat in the C9orf72 gene, while his symptomatic youngest sister had a heterozygous 159 repeat. The patient and his sister exhibited more pronounced cortical thinning in the frontotemporoparietal areas. The discrepancy observed between the distribution of atrophy and the presentation of symptoms in patients with C9orf72 pathogenic repeat expansion may be attributable to the slow progression of their clinical course over time. The variable symptom presentation of C9orf72 pathogenic repeat expansion highlights the importance of considering this pathogenic variant as a potential cause of autosomal dominant degenerative brain diseases beyond FTD and ALS.
© 2023 American Academy of Neurology.