Recurrent Rhabdomyolysis in a Heterozygous DYSF Variant Carrier

Introduction: Recurrent rhabdomyolysis in young patients without clear triggers can be diagnostically challenging. Dysferlinopathies like limb-girdle muscular dystrophy type 2B are autosomal recessive, typically requiring two pathogenic variants. This case explores the diagnostic complexity of recurrent rhabdomyolysis in a heterozygous DYSF variant carrier Case Description: A 19-year-old female with hypertension and multiple episodes of rhabdomyolysis was evaluated for recurrent acute kidney injury, including one episode requiring hemodialysis. Her first episode occurred at age 14 after a viral illness, presenting with severe muscle pain, fatigue, and dark urine. Creatine kinase (CK) exceeded 200,000 U/L. At 16, she had a second episode two days after her second COVID-19 vaccine, with CK over 100,000 U/L. A third episode followed pharyngitis, leading to hospitalization, aggressive fluids, and hemodialysis. Between episodes, she reported chronic fatigue but denied myalgia or exercise intolerance. Examination showed normal muscle tone, full strength, and intact cranial nerves. Laboratory tests, including muscle enzymes and autoimmune markers, were unremarkable. Given recurrent severe rhabdomyolysis without clear triggers such as trauma or exertion, genetic testing was pursued. Discussion: Whole exome sequencing revealed a heterozygous pathogenic variant in the DYSF gene (c.2643+1G>A), encoding dysferlin, essential for muscle membrane repair. Dysferlinopathies are classically recessive, but heterozygous carriers can have symptoms due to incomplete penetrance. This patient likely represents such a case, with early symptom onset despite a single variant. She was counseled to avoid strenuous activity and maintain hydration to prevent further episodes. Since then, she has remained symptom-free with stable kidney function. This case highlights the evolving understanding of heterozygous variants in genetic muscle diseases. It emphasizes genetic testing’s value in unexplained recurrent rhabdomyolysis to guide personalized management and prevent complications such as kidney injury.