Early-Onset Alström Syndrome: Clinical Clues from a Pediatric Case Series

Abstract: Background; Alström syndrome (AS) is characterized by core clinical features, including cone-rod dystrophy, early-onset obesity, progressive bilateral sensorineural hearing loss, type 2 diabetes mellitus, and cardiomyopathy. Agespecific diagnostic criteria have been proposed. Early diagnosis is critical due to the variable and progressive nature of clinical manifestations. The limited number of reported cases hinders a comprehensive understanding of the natural history of the disease. Methods; We present three pediatric cases of AS, highlighting the syndrome’s clinical variability and discussing the challenges of early diagnosis in the pediatric age. Results; Case 1 involves a 4-year-old girl who presented with nystagmus, poor vision, photophobia, and sensorineural hearing loss starting at 3 months of age, later developing type 2 diabetes and early-stage dilated cardiomyopathy. Cases 2 and 3 illustrate marked intrafamilial phenotypic variability, with one sibling experiencing fatal neonatal cardiomyopathy and the other presenting a milder clinical course. Conclusions; Our cases show that the clinical features of AS evolve over time, with ocular manifestations appearing in early infancy and others emerging later. Significant intrafamilial phenotypic variability underscores the need for individualized clinical management, even within the same family. Given the potential for rapid and fatal progression of cardiomyopathy in infancy, early cardiac screening is strongly recommended in patients with early-onset nystagmus and in all individuals diagnosed with AS.