ALS in Finland: Major Genetic Variants and Clinical Characteristics of Patients With and Without the C9orf72 Hexanucleotide Repeat Expansion

• Published in: Neurology. Genetics Vol. 8; no. 2; p. e665
• Main Authors: Laaksovirta, Hannu, Launes, Jyrki, Jansson, Lilja, Traynor, Bryan J, Kaivola, Karri, Tienari, Pentti J
• Format: Journal Article
• Language: English
• Published: United States 01.04.2022
• ISSN: 2376-7839; 2376-7839
• DOI: 10.1212/NXG.0000000000000665

To analyze the frequencies of major genetic variants and the clinical features in Finnish patients with amyotrophic lateral sclerosis (ALS) with or without the hexanucleotide repeat expansion. A cohort of patients with motor neuron disease was recruited between 1993 and 2020 at the Helsinki University Hospital and 2 second-degree outpatient clinics in Helsinki. Finnish ancestry patients with ALS fulfilled the diagnosis according to the revised El Escorial criteria and the Awaji-criteria. Two categories of familial ALS (FALS) were used. A patient was defined FALS-A if at least 1 first- or second-degree family member had ALS, and FALS-NP, if family members had additional neurologic or psychiatric endophenotypes. Of the 815 patients, 25% had FALS-A and 45% FALS-NP. expansion ( ) was found in 256 (31%) of all patients, in 58% of FALS-A category, in 48% of FALS-NP category, and in 23 or 17% of sporadic cases using the FALS-A or FALS-NP definition. or p.D91A homozygosity was found in 328 (40%) of the 815 patients. We compared demographic and clinical characteristics between and patients with unknown cause of ALS ( ). We found that the age at onset was significantly earlier and survival markedly shorter in the vs patients with ALS. The shortest survival was found in bulbar-onset male patients, whereas the longest survival was found in limb-onset males. Older age at onset associated consistently with shorter survival in and patients in both limb-onset and bulbar-onset groups. There were no significant differences in the frequencies of bulbar-onset and limb-onset patients in and groups. ALS-frontotemporal dementia (FTD) was more common in (17%) than in (4%) patients, and of all patients with ALS-FTD, 70% were . These results provide further evidence for the short survival of -associated ALS. A prominent role of the and variants was found in the Finnish population. An unusually high frequency of was also found among patients with sporadic ALS. The enrichment of these 2 variants likely contributes to the high incidence of ALS in Finland.