Familial Multiple Sclerosis: A Global Perspective on Prevalence and Contributing Factors
Multiple sclerosis (MS) is a complex, immune-mediated, neurodegenerative disease that primarily affects the central nervous system. Its clinical presentation can vary significantly, but it often leads to debilitating neurological impairment in young adults. Familial multiple sclerosis (FMS), where more than one family member is affected, highlights the role of genetic factors in MS susceptibility, though environmental triggers also play a substantial role. A recent research published by Ehtesham et al. (2021) offers insights into the global prevalence of FMS, emphasizing differences based on geography, sex, and age of onset.
Global Prevalence and Age of Onset
The pooled prevalence of MS in families was estimated to be 11.8% across 49 studies included in the analysis. This figure, while slightly lower than a prior estimate of 12.6%, suggests that approximately 1 in 10 individuals with MS have a family member also affected by the condition. Interestingly, the prevalence of FMS was found to be significantly higher in pediatric-onset MS (POMS) cases (15.5%) than in adult-onset cases (AOMS), which showed a prevalence of 10.8%. The mean age of disease onset in FMS cases was also slightly younger, at 28.7 years.
These findings suggest that genetic factors play a larger role in earlier-onset MS, with a higher genetic load potentially contributing to the earlier manifestation of symptoms. The association between the HLA-DRB1*15:01 allele and an earlier onset supports this theory, as the allele is known to reduce the age of symptom onset in MS patients.
Sex Differences in FMS
One key finding of the study is the lack of a significant sex difference in FMS prevalence. While MS is generally more common in females, the meta-analysis showed that FMS affects men and women at similar rates (13.7% in men versus 15.4% in women). This challenges the "Carter effect" hypothesis, which posits that the less commonly affected sex in a disease (in this case, men) may have a higher genetic load and thus a higher likelihood of passing the disease to offspring.
Geographical Variation and Environmental Influences
The study also revealed significant geographical variation in FMS prevalence, with higher rates in some regions, such as the Middle East, compared to others like Europe. A meta-regression analysis showed that FMS prevalence decreases with increasing latitude and MS prevalence. This finding is somewhat surprising, as MS is generally more common at higher latitudes, likely due to lower sunlight exposure and vitamin D deficiency.
The authors hypothesize that as MS becomes more prevalent in a population, increased public awareness and genetic counseling may lead to a reduction in consanguineous marriages or other high-risk family structures, ultimately reducing FMS prevalence. However, they note that cultural and social factors, including marriage patterns and healthcare access, likely also play a role in these regional differences.
Implications for Understanding MS Risk
The study underscores the importance of both genetic and environmental factors in MS development. While familial cases account for a relatively small proportion of total MS cases, they offer valuable insights into the genetic underpinnings of the disease. Identifying these genetic risk factors could lead to improved screening and early interventions for individuals at higher risk.
Moreover, the findings related to pediatric MS highlight the need for further research into the genetic factors that contribute to early-onset MS. Given the higher prevalence of FMS in pediatric cases, genetic screening may be particularly beneficial in families with a history of early-onset MS.
Conclusion
This comprehensive review of familial multiple sclerosis presents a nuanced picture of the factors contributing to MS risk, emphasizing the interplay between genetics, environment, and geography. While the global prevalence of FMS is relatively stable, significant variations based on age, sex, and location suggest that future research should focus on understanding these differences and their underlying causes. By improving our understanding of FMS, we can develop more targeted strategies for prevention, diagnosis, and treatment, particularly in high-risk populations.
This meta-analysis highlights the complex nature of MS and the need for continued investigation into both its genetic and environmental determinants. With further research, it may be possible to identify individuals at higher risk of developing MS and provide early interventions that could delay or even prevent the onset of symptoms.
Reference:
Ehtesham, N., Rafie, M.Z. & Mosallaei, M. The global prevalence of familial multiple sclerosis: an updated systematic review and meta-analysis. BMC Neurol 21, 246 (2021).