The Global Prevalence of Familial Multiple Sclerosis: A Comprehensive Overview
Multiple Sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system with varying clinical presentations. While the exact cause of MS remains unclear, it is widely believed to result from a complex interplay between genetic predispositions and environmental factors. Familial Multiple Sclerosis (FMS), where MS is observed in multiple family members, adds another layer of complexity to understanding this disease. A recent systematic review sheds light on the worldwide prevalence of FMS and highlights significant findings in the field.
Understanding Familial Multiple Sclerosis
FMS is defined as cases of MS where at least one family member, typically within the first to third degree, also has MS. The notion that MS could run in families was first reported in 1933 by Curtius and Speer, and subsequent studies have continually supported the idea of genetic susceptibility in MS. Research has identified over 100 genes or gene loci associated with MS, and studies on twins and familial aggregation have shown high concordance rates, suggesting a strong genetic component.
To estimate the prevalence of FMS globally, researchers conducted an extensive literature search using databases like PubMed, Web of Science, and Scopus, covering studies published from 1954 to 2016. The study included articles that met specific criteria, such as a neurologist’s diagnosis of MS and clear descriptions of familial cases. Ultimately, 17 studies encompassing a total of 14,619 MS patients were analyzed using MedCalc software to estimate pooled prevalence.
Key Findings
The analysis revealed that the prevalence of FMS is approximately 12.6% among MS patients worldwide, with a 95% confidence interval ranging from 9.6% to 15.9%. However, significant heterogeneity was observed across different regions, with prevalence rates ranging from as low as 2% in Hungary to as high as 32.7% in Saskatchewan, Canada. This wide variation indicates that factors beyond genetics, such as environmental influences, likely play a substantial role in the prevalence of FMS.
Genetic and Environmental Influences
The study found no consistent relationship between FMS prevalence and factors like latitude or ethnicity, suggesting that both genetic and environmental factors contribute to MS susceptibility. Some candidate genes linked to MS include those encoding myelin basic protein (MBP), proteolipid protein (PLP), and myelin oligodendrocyte glycoprotein (MOG). Additionally, microRNA (miRNA) profiles have shown potential in distinguishing between familial and sporadic MS cases.
Environmental factors such as Epstein-Barr Virus (EBV) infection, smoking, and vitamin D levels, influenced by sun exposure, have also been implicated in MS risk. Interestingly, the review highlighted regions with similar genetic backgrounds but differing FMS prevalence rates, further supporting the complex interaction between genetics and environment.
Regional Disparities
The review noted that certain regions exhibited consistent FMS prevalence rates across multiple studies. For instance, studies from Iran showed a prevalence of 11-12.2%, while regions like Saskatchewan, Finland, and Croatia-Slovenia reported higher rates, potentially reflecting regional environmental conditions or genetic predispositions.
Conversely, regions like Hungary, Mexico, and Brazil exhibited lower prevalence rates. These discrepancies underscore the need for further research to understand the underlying causes of these variations and to explore the potential role of rare genetic variants and environmental factors in FMS.
Conclusion and Future Directions
The study concludes that the prevalence of FMS is not solely dependent on genetic or environmental factors but rather on their cumulative and interactive effects. This significant heterogeneity in FMS prevalence calls for more comprehensive studies focusing on both genetic and environmental contributions to MS.
Future research should aim to investigate the prevalence of FMS in underrepresented regions and explore the specific genetic and environmental factors contributing to MS in families. Understanding these dynamics will be crucial in developing targeted interventions and improving outcomes for individuals with MS.
In summary, this systematic review provide a critical overview of the global prevalence of FMS, highlighting the intricate interplay of genetics and environment in the etiology of MS. By shedding light on these complexities, the study paves the way for future research and better management strategies for MS patients worldwide.
Reference:
Harirchian, M. H., Fatehi, F., Sarraf, P., Honarvar, N. M., & Bitarafan, S. (2018). Worldwide prevalence of familial multiple sclerosis: A systematic review and meta-analysis. Multiple sclerosis and related disorders, 20, 43-47.
