Genetic and phenotypic landscape of hypertrophic cardiomyopathy in the MENA region: a systematic review

Background Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy, and it is a leading cause of sudden cardiac death (SCD) in young people. Recessive genetic disorders are especially prevalent in the Middle East and North Africa (MENA) region due to consanguinity, which affects the genetic landscape of hereditary disorders. Here we conducted a systematic review of mutations in patients with HCM in the MENA and report genotype-phenotype associations to provide an evidence base for personalized diagnostic and therapeutic interventions. Methods We systematically searched the PubMed, ProQuest, and Scopus databases from inception until October 2025 to collect all genetic data and phenotypes of patients with HCM in the MENA. Broad search terms were used to capture all relevant literature describing genetic variants associated with HCM in the MENA region including inheritance patterns and genotype-phenotype associations. Results The database search returned 448 studies, with 17 meeting inclusion criteria. 14 studies were case series, 2 studies were case reports, and 1 was a case-control study. In 1323 HCM subjects in the MENA, there were 107 genetic variants in 21 genes. The majority of the variants occurred in MYBPC3 and MYH7, consistent with other populations. However, there were also homozygous variants in recessive genes, founder mutations, and novel variants in non-sarcomeric genes in the region, with patients experiencing more severe clinical phenotypes. Conclusion To our knowledge, this is the first systematic review on genetic variants associated with HCM in the MENA region. The genetic landscape of HCM is complex and unique in the MENA. The underrepresentation of MENA populations in global genomic resources remains a barrier to variant interpretation. Region-specific gene panels may be required to advance the diagnosis of HCM in the region.