Familial benign frontotemporal deterioration with C9ORF72 hexanucleotide expansion

Abstract

Background: In recent years, a benign variant of frontotemporal lobar degeneration (FTLD) has been recognized, with a particularly slow progression of cognitive deficits and scarce frontotemporal atrophy or hypoperfusion in neuroimaging studies. Patients with FTLD have been considered "phenocopies," with an underlying nondegenerative neurologic process.

Results: We report the first family with three affected members having benign FTLD associated with C9ORF72 gene hexanucleotide expansion. Onset of symptoms occurred during the fifth decade, with naming and memory problems as the main features. Two siblings have stabilized at mild cognitive impairment or incipient dementia for more than a decade, and remain quite independent for their activities of daily living at the current ages of 69 and 65 years, respectively. Their mother's cognitive deterioration evolved slowly during >30 years.

Conclusion: This family demonstrates that a benign evolution can be part of the growing spectrum of clinical phenotypes associated with neurodegenerative diseases caused by the C9ORF72 hexanucleotide expansion. Screening of this genetic marker should be considered in cases with this slow deterioration, especially if there is a family history.

Keywords: C9ORF72 gene; Frontotemporal dementia; Hexanucleotide expansion; Neurogenetics.