Determining the incidence of familiality in ALS: A study of temporal trends in Ireland from 1994 to 2016. (June 2018)

• Record Type: Journal Article
• Authors: Ryan, Marie; Heverin, Mark; Doherty, Mark A.; Davis, Nicola; Corr, Emma M.; Vajda, Alice; Pender, Niall; McLaughlin, Russell; Hardiman, Orla
• Is Part Of: Neurology. Volume 4:Number 3(2018)
• Publication Date: 2018-06
• Subjects: Neurogenetics -- Periodicals; 616.80442
• DOI: 10.1212/NXG.0000000000000239
• Languages: English
• ISSNs: 2376-7839

Abstract

Abstract : Objective: To assess temporal trends in familial amyotrophic lateral sclerosis (FALS) incidence rates in an Irish population and to determine factors influencing FALS ascertainment. Methods: Population-based data collected over 23 years, using the Irish amyotrophic lateral sclerosis (ALS) register and DNA biobank, were analyzed and age-standardized rates of FALS and associated familial neuropsychiatric endophenotypes were identified. Results: Between 1994 and 2016, 269 patients with a family history of ALS from 197 unique families were included on the register. Using stringent diagnostic criteria for FALS, the mean age-standardized FALS incidence rate for the study period was 11.1% (95% confidence interval [CI], 8.8–13.4). The FALS incidence rate increased steadily from 5.2% in 1994 to 19.1% in 2016, an annual increase of 0.7% (95% CI, 0.5–0.9, p < 0.0001). Inclusion of the presence of neuropsychiatric endophenotypes within kindreds increased the FALS incidence rate to 30%. The incidence of FALS in newly diagnosed individuals from known families increased significantly with time, accounting for 50% of all FALS diagnoses by 2016. The mean annual rate of recategorization from "sporadic ALS" to "FALS" was 3% (95% CI, 2.6–3.8). Conclusions: The true population-based rate of FALS is at least 20%. Inclusion of extended endophenotypes within kindreds increases the rate of FALS to 30%. Cross-sectional analysis of clinic-based cohorts and stringent definitions of FALS underestimate the true rate of familial disease. This has implications for genetic counseling and in the recognition of presymptomatic stages of ALS.