Amyotrophic lateral sclerosis caused by the C9orf72 expansion in Norway - prevalence, ancestry, clinical characteristics and sociodemographic status.

Objective: The most common genetic cause of amyotrophic lateral sclerosis (ALS) is the C9orf72 expansion. A high incidence of this expansion has been detected in Sweden and Finland. This Norwegian population-based study aimed to identify the prevalence, geographic distribution, ancestry, and relatedness of ALS patients with a C9orf72 expansion (C9 _pos ). Further, we compared C9 _pos and C9 _neg patients' clinical presentation, family history of ALS and other neurodegenerative disorders, and sociodemographic status.
Methods: We recruited ALS patients from all 17 Departments of neurology in Norway. Blood samples and questionnaires regarding clinical characteristics, sociodemographic status and family history of ALS, and other neurodegenerative disorders were collected. The C9orf72 expansion was examined for all patients.
Results: The study enrolled 500 ALS patients, 8.8% of whom were C9 _pos , with half being sporadic ALS cases. The proportion of C9 _pos cases differed between regions, ranging from 17.9% in the Northern region to 1.9% in the Western region. The majority of C9 _pos patients had non-Finnish European descent and were not closely related. C9 _pos patients exhibited a significantly shorter mean survival time, had a higher frequency of relatives with ALS or dementia, and were more often unmarried/single and childless than C9 _neg patients.
Conclusion: C9 _pos patients constitute a large portion of the Norwegian ALS population. Ancestry and relatedness do not adequately explain regional differences. Relying on clinical information to identify C9 _pos patients has proven to be challenging. Half of C9 _pos patients were reported as having sporadic ALS, underlining the importance of carefully assessing family history and the need for genetic testing.