Abstract / Summary
Inherited arrhythmias and cardiomyopathies are leading causes of sudden cardiac death in young individuals. Although global registries and genetic databases have advanced diagnosis and prevention globally, data from the Middle East (ME) remain limited and fragmented. This review synthesizes clinical and genetic evidence on long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome, arrhythmogenic right ventricular cardiomyopathy, hypertrophic cardiomyopathy, and dilated cardiomyopathy across the ME. A defining feature of ME cohorts is the high prevalence of consanguinity, which shapes a distinctive genetic and clinical landscape across these conditions. Autosomal recessive inheritance is consistently enriched, producing homozygous genotypes, which frequently manifest as earlier onset and more aggressive clinical phenotypes compared with those in non-ME populations. Population-specific founder variants have been identified across multiple conditions, whereas consanguineous pedigrees have contributed to the discovery of novel disease genes and recessive mechanisms that expand the global genetic landscape of inherited cardiovascular disease. However, a disproportionately high burden of variants of uncertain significance persists across conditions, driven largely by underrepresentation of ME populations in global genomic reference databases. Emerging large-scale genome initiatives such as the Qatar Biobank, the Egyptian Genome Project, and the Greater Middle East Variome offer a viable path toward ancestry-specific variant interpretation. Strengthening regional registries, genomic resources, and family-based screening programs will be essential to improving risk stratification and prevention of sudden cardiac death in the ME.