Phenotypic spectrum of Alström syndrome in a Saudi cohort: Eight genetically confirmed cases

Abstract: PURPOSE: Alström syndrome (AS) is a rare autosomal recessive disorder caused by mutations in the ALMS1 gene, resulting in multisystemic manifestations, including cone-rod dystrophy and obesity. This study investigates AS in Saudi Arabia, where a high rate of consanguinity influences its prevalence. METHODS: We conducted a retrospective case series of eight patients from six families diagnosed with early-onset retinal dysfunction associated with ALMS1 mutations. Evaluations were performed at two tertiary care centers, including comprehensive ophthalmic examinations and genetic testing. RESULTS: All patients exhibited severe visual impairment, commonly presenting with photophobia and nystagmus. Systemic manifestations included cardiomyopathy (75%) and obesity (37.5%). Genetic testing confirmed pathogenic variants in ALMS1 for all individuals, with a 100% consanguinity rate. Notable mutations identified included c.2723C>G and c.8164C>T. CONCLUSION: This case series enhances the understanding of AS in Saudi Arabia and emphasizes the need to raise awareness among healthcare professionals. Early detection of symptoms is essential for timely interventions and improve clinical outcomes. Future research should focus on elucidating the molecular mechanisms underlying phenotypic variability with the goal of improving diagnostic accuracy and developing targeted therapeutic strategies.