Clinical Characteristics of C9ORF72-Linked Frontotemporal Lobar Degeneration

• Main Authors: Anna-Lotta Kaivorinne, Michaela K. Bode, Liisa Paavola, Hannu Tuominen, Mika Kallio, Alan E. Renton, Bryan J. Traynor, Virpi Moilanen, Anne M. Remes
• Format: Article
• Language: English
• Published: Karger Publishers 2013-08-01
• Series: Dementia and Geriatric Cognitive Disorders Extra
• Subjects: Association study; Clinical features; Frontotemporal dementia; Frontotemporal lobar degeneration; Genetics
• Online Access: http://www.karger.com/Article/FullText/351859

Background: The most common genetic cause of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) has been linked to a hexanucleotide repeat expansion in the C9ORF72 gene. The frequency of the C9ORF72 expansion in Finland is among the highest in the world. Methods: We assessed 73 Finnish patients with FTLD in order to examine the clinical characteristics associated with the expanded C9ORF72. Demographic and clinical features were evaluated. As a potential disease modifier, the apolipoprotein E (APOE) genotype was also assessed. Neuropathological analysis was available on 2 expansion carriers and 1 non-carrier. Results: The C9ORF72 expansion was present in 20 of 70 (29%) probands. Significant associations with the C9ORF72 expansion were observed for concomitant ALS and positive family history of dementia or ALS. Psychoses were detected in both carriers and non-carriers (21 vs. 10%, p = 0.25). The APOE ε4 allele did not cluster among expansion carriers. Numerous p62-positive neuronal inclusions were detected in the cerebellar cortex of the 2 expansion carriers. Conclusion: In line with the suggested C9ORF72 core phenotype, we also detected a high frequency of neuropsychiatric symptoms; however, these symptoms seem not be specific to C9ORF72-associated FTLD. FTLD should be considered in cases of middle-age-onset psychosis.