Semantic Variant Primary Progressive Aphasia Associated with the C9orf72 Hexanucleotide Expansion – A Longitudinal Case Report (P13-6.004)

Abstract

<h3>Objective:</h3> To highlight a rare phenotypic expression of the chromosome 9 open reading frame 72 (<i>C9orf72</i>) hexanucleotide expansion, and showcase three years of clinical, neuropsychological, MRI, and FDG-PET data. <h3>Background:</h3> The <i>C9orf72</i> 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. <h3>Design/Methods:</h3> Case report. <h3>Results:</h3> The patient is a member of a large FTD/ALS kindred with the <i>C9orf72</i> 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 <i>C9orf72</i>. He now carries the diagnosis of semantic variant primary progressive aphasia (svPPA) and continues to be followed longitudinally. <h3>Conclusions:</h3> This report characterizes the clinical, neuropsychological, and multimodal neuroimaging findings that are typical of svPPA, which in this case is associated with the <i>C9orf72</i> expansion. This case displays the importance of assessing language in patients with a known <i>C9orf72</i> expansion when determining if a cognitive syndrome is present. <b>Disclosure:</b> Dr. Switzer has nothing to disclose. The institution of Dr. Fields has received research support from National Institutes of Health. The institution of Dr. Fields has received research support from Patient-Centered Outcomes Research Institute. The institution of Dr. Kantarci has received research support from Eli Lilly. The institution of Dr. Kantarci has received research support from NIH. The institution of Dr. Kantarci has received research support from ADDF. Dr. Lowe has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for AVID Radiopharmaceutical. Dr. Lowe has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai Inc. The institution of Dr. Lowe has received research support from AVID Radiopharmaceuticals. Dr. Corriveau-Lecavalier has nothing to disclose. Dr. Jones has nothing to disclose. Dr. Botha has received research support from NIH. Dr. Knopman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for DIAN TU study. The institution of Dr. Knopman has received research support from NIH. Dr. Ramanan has nothing to disclose. Dr. Gavrilova has nothing to disclose. The institution of Maria Lapid has received research support from NIA. Ms. Forsberg has nothing to disclose. Mr. Nelson has nothing to disclose. Mr. Kolander has nothing to disclose. Dr. Boeve has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Rainwater Charitable Foundation. The institution of Dr. Boeve has received research support from Alector. The institution of Dr. Boeve has received research support from GE Healthcare. The institution of Dr. Boeve has received research support from Transposon. The institution of Dr. Boeve has received research support from Cognition Therapeutics. Dr. Boeve has received publishing royalties from a publication relating to health care.