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Background: The rising prevalence of familial multiple sclerosis (MS) in Iran has spurred interest in the potential impact of parental consanguinity on the risk of developing the disease. This study aims to aggregate current knowledge on parental consanguinity and its possible effect on MS risk, particularly among familial MS patients from various regions and ethnicities in Iran. The objective is to enhance the understanding of MS genetics and encourage further research in this field., Materials and Methods: A cross-sectional study was conducted on clinically definite familial MS (FMS) patients registered in the nationwide MS registry of Iran (NMSRI). Data were extracted and supplemented with structured telephone follow-ups to gather detailed histories of MS in relatives and the familial relationships of the patients' parents. A family penetration score was proposed. Descriptive statistics and inferential statistical tests were used to analyze the data at a significance level of 0.05, adhering to ethical guidelines., Results: Out of 19,911 individuals registered in the NMSRI, 2307 FMS patients across 13 provinces were included in the final analysis. Among these, 385 (19.3 %) reported parental consanguinity, with 283 (14.2 %) having parents who were cousins and 102 (5.1 %) having parents who were distant relatives. The data showed no significant association between parental kinship and variables such as MS phenotype, number of affected relatives with MS, hospitalization rates, and expanded disability status scale score. Similarly, MS severity did not differ based on parental consanguinity ( P -value >0.05). While the rate of consanguineous marriage was higher among patients with an onset age less than 18 years, there was no statistically significant difference in disease onset age based on parental consanguinity status., Conclusion: Our study highlights the complexity of factors influencing MS development, including genetic and environmental components. These results highlight the need for further research to achieve a more comprehensive understanding of MS etiology., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Sharareh Eskandarieh reports financial support was provided by 10.13039/501100004484Tehran University of Medical Sciences. Sharareh Eskandarieh reports a relationship with 10.13039/501100004484Tehran University of Medical Sciences that includes: consulting or advisory, employment, equity or stocks, and funding grants. Sharareh Eskandarieh has patent licensed to NMSRI. None If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Support for the Reported Work: Tehran University of Medical Sciences. Relevant support: advisory positions, consulting fees. Intellectual Property: National multiple sclerosis registry system of Iran (NMSRI). Other Activities: None. The entire data of the study has been sent to the journal in Excel file format. If needed, it will be provided by contacting the website https://nmsri.ir/or by email., (© 2024 The Authors.)