Semantic Variant Primary Progressive Aphasia Associated with the C9orf72 Hexanucleotide Expansion – A Longitudinal Case Report
Aaron Switzer1, Julie Fields1, Kejal Kantarci1, Val Lowe1, Nick Corriveau-Lecavalier1, David Jones1, Hugo Botha1, David Knopman1, Vijay Ramanan1, Ralitza Gavrilova1, Maria Lapid1, Leah Forsberg1, Kevin Nelson1, Tyler Kolander1, Bradley Boeve1
1Behavioral neurology, Mayo Clinic
Objective:
To highlight a rare phenotypic expression of the chromosome 9 open reading frame 72 (C9orf72) hexanucleotide expansion, and showcase three years of clinical, neuropsychological, MRI, and FDG-PET data.
Background:
The C9orf72 expansion is associated with frontotemporal dementia, parkinsonism, ALS, or some combination of these phenotypes. Of the FTD variants, the behavioral variant FTD phenotype is most common. Language variants are rare, and there is little longitudinal data on such cases.
Design/Methods:
Case report.
Results:
The patient is a member of a large FTD/ALS kindred with the
C9orf72 expansion, and he has been followed longitudinally with annual visits over 3 years (4 evaluations) in the ALLFTD (
www.allftd.org) natural history research program focused on frontotemporal lobar degeneration. At age 67 he began experiencing mild word finding difficulties, trouble identifying objects on a shopping list, and mild face blindness. These symptoms have progressed, and other than mild memory impairment and mild apathy, there are no other significant cognitive/behavioral/motor features. Neuropsychological testing has shown progressive deficits in high frequency object naming and loss of semantic word knowledge. MRI has demonstrated progressive atrophy of the left anterior temporal lobe. FDG-PET has shown progressive hypometabolism predominantly in the left anterior temporal lobe, with mild involvement of the prefrontal, cingulate, and parietal cortices. Clinical genetic testing has confirmed the presence of the hexanucleotide expansion in
C9orf72. He now carries the diagnosis of semantic variant primary progressive aphasia (svPPA) and continues to be followed longitudinally.
Conclusions:
This report characterizes the clinical, neuropsychological, and multimodal neuroimaging findings that are typical of svPPA, which in this case is associated with the C9orf72 expansion. This case displays the importance of assessing language in patients with a known C9orf72 expansion when determining if a cognitive syndrome is present.