Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disorder. Familial (fALS) cases are usually reported to constitute 5%–10% of all ALS cases; however, no recent literature review or meta-analysis of this proportion (referred to throughout as "proportion fALS") has been conducted. Our objective was to estimate the proportion fALS by geographic region and to assess the effect of study characteristics on the estimates.

A comprehensive literature review was performed to identify all original studies reporting the number of fALS cases in an ALS cohort. The results were stratified by geographic region, study design (case series or population-based), and decade of study publication. Subgroup analyses were conducted according to family history criteria used to define fALS. We report pooled estimates of the proportion fALS from random-effects meta-analyses when >2 studies are available and I² is < 90%; weighted averages and ranges are otherwise presented.

The overall pooled proportion fALS based on a total 165 studies was 8% (0%, 71%). The proportion fALS was 9% (0%, 71%) among 107 case series and 5% (4%, 6%) among 58 population-based studies. Among population-based studies, proportion fALS by geographic region was 6% (5%, 7%; N = 37) for Europe, 5% (3%, 7%; N = 5) for Latin America, and 5% (4%, 7%; N = 12) for North America. Criteria used to define fALS were reported by 21 population-based studies (36%), and proportion fALS was 5% (4%, 5%; N = 9) for first-degree relative, 7% (4%, 11%; N = 4) for first or second-degree relative, and 11% (N = 1) for more distant ALS family history. Population-based studies published in the 2000s or earlier generated a lower pooled proportion fALS than studies published in the 2010s or later.

The results suggest that variability in the reported proportion fALS in the literature may be, in part, due to the differences in geography, study design, fALS definition, and decade of case ascertainment. Few studies outside of European ancestral populations were available. The proportion fALS was marginally higher among case series compared with population-based studies, likely because of referral bias. Criteria used to define fALS were largely unreported. Consensus criteria for fALS and additional population-based studies in non-European ancestral populations are needed.