Consanguineous Marriage and Familial Multiple Sclerosis: Insights from a National Registry-Based Study in Iran

Multiple sclerosis (MS) is a complex autoimmune disorder that affects the central nervous system, leading to a range of physical and cognitive disabilities. While the precise etiology of MS remains elusive, both genetic and environmental factors are recognized as significant contributors to disease susceptibility. In Iran, the prevalence of MS has been increasing, prompting research into potential genetic influences, including the impact of parental consanguinity on MS risk, particularly among familial MS (FMS) patients.

Consanguineous marriage, the union between individuals with shared ancestry, is a common practice in certain regions and has been linked to an increased risk of various hereditary diseases. This study aimed to investigate the potential impact of parental consanguinity on MS risk among familial MS patients in Iran, using data from the Nationwide MS Registry of Iran (NMSRI). By examining the prevalence and effects of consanguineous marriage among FMS patients, the study sought to enhance the understanding of MS genetics and encourage further research in this field.

A cross-sectional study design was employed, involving 2307 FMS patients from the NMSRI. Data were collected through both registry records and structured telephone follow-ups to gather detailed family histories and information on parental relationships. The study proposed a family penetration score to quantify the extent of family involvement in MS.

Results
The study population included 2307 FMS patients, with a female to male ratio of 3.07:1. Among these patients, 19.3% reported parental consanguinity, with 14.2% having parents who were cousins and 5.1% having parents who were distant relatives. Key findings of the study included:

Age of Onset: While the rate of consanguineous marriage was higher among patients with an onset age of less than 18 years, there was no statistically significant difference in disease onset age based on parental consanguinity status.

Sex Differences: Males exhibited higher EDSS scores and a higher frequency of progression to secondary progressive MS (SPMS) compared to females. However, no significant sex differences were observed in terms of the number of family members affected by MS or the prevalence of consanguinity.

Discussion
The findings highlight the complexity of factors influencing MS development, including genetic and environmental components. Despite the higher prevalence of consanguinity among certain populations, the study found no significant impact of parental consanguinity on MS risk or severity. This aligns with some previous studies but contrasts with others that have suggested a potential role for consanguinity in increasing MS risk.

Implications for Future Research
The study underscores the need for further research to elucidate the genetic and environmental factors contributing to MS. Longitudinal studies tracking disease progression in patients with a history of parental consanguinity could provide deeper insights into the potential causal relationships. Additionally, genetic studies focusing on specific variations associated with familial MS in consanguineous populations could enhance the understanding of MS pathogenesis.

Conclusion
This national registry-based study in Iran contributes valuable data to the ongoing exploration of MS genetics. While no significant association was found between parental consanguinity and MS risk or severity, the findings emphasize the multifactorial nature of MS and the importance of continued research in diverse populations. By advancing the understanding of MS etiology, such studies can inform potential interventions and improve disease management strategies.

Reference:
Salehi, Z., Naghizadeh, M. M., Ezabadi, S. G., Ebrahimitirtashi, A., Kasbi, N. A., Khodaie, F., ... & Eskandarieh, S. (2024). Consanguineous marriage among familial multiple sclerosis subjects: A national registry-based study. Heliyon.