The global prevalence of familial multiple sclerosis: an updated systematic review and meta-analysis

Abstract

Background: Considering that familial multiple sclerosis (FMS) can reveal the extent to which genetic and environmental factors each involve in the etiopathogenesis of the disease, we performed an updated meta-analysis of the worldwide prevalence of FMS by addition of recent publications. Methods: A search in PubMed, Scopus, the ISI Web of Science, and Google Scholar up to 20 December 2020 was done. The inclusion criteria were based on the CoCoPop approach (condition, context, and population). The qualified studies entered the process of the meta-analysis by using comprehensive meta-analysis ver. 2 software.Results: The pooled prevalence of MS in relatives of 16179 FMS cases was estimated to be 11.8% (95% CI: 10.7-13) based on a random-effects model. The pooled mean age of disease onset in adult probands was calculated to be 28.7 years (95% CI: 27.2± 30.2). In 13 studies that reported the data of FMS in pediatrics (n=6636) and adults (n=877), the FMS prevalence was 10.8% (95% CI: 8.1-14.2) and 15.5% (95% CI: 13.8-17.4), respectively. Considering the data of 9 studies, the prevalence of FMS in males (n=5243) and females (n=11503) patients was calculated to be 13.7% (95% CI: 10.1-18.2) and 15.4% (95% CI: 10.3-22.4), respectively. The odds ratio of male/female in FMS cases was not statistically significant (OR= 0.9; 95% CI: 0.6-1.2, P=0.55). Subgroup analysis demonstrated a significant difference in the prevalence of FMS between the geographical areas (P= 0.007). The meta-regression model for FMS prevalence was significantly lower in terms of higher latitude (P< 0.001) and increased MS prevalence (P< 0.001). In contrast, meta-regression based on prevalence day was not statistically significant (P=0.29).Conclusions: The prevalence of FMS is more in the pediatric group than that of adults, is distinct between geographical areas, and diminishes with the increment of MS prevalence and latitude. Also, the symptoms initiate relatively at lower ages in FMS cases. By contrast with multifactorial diseases, our analysis unveiled that the prevalence of FMS was not more prevalent in men than women and the risk of MS development in relatives was not more when the affected proband was male.