Expanding the Clinical and Genetic Spectrum of Caveolinopathy in Korea

Purpose: Caveolinopathy is a disease caused by caveolin-3 (CAV3) mutations that shows a wide clinical spectrum, including isolated hyperCKemia and limb-girdle muscular dystrophy. While recent advances in next-generation sequencing (NGS) have enabled earlier diagnosis of this disease, it remains difficult to predict the clinical course of each patient.Methods: This study summarizes the clinical presentations of 13 genetically confirmed caveolinopathy patients in four Korean families. Genetic diagnosis was performed using NGS technologies for probands and Sanger sequencing for the other family members.Results: Four coding mutations were found (p.Val103_Val104del, p.Asp28Glu, p.Pro105Leu, and p.Arg27Gln), and each family showed autosomal dominant inheritance. While all 13 cases had hyperCKemia, only five of them showed some myopathic features including ankle contracture, calf hypertrophy, exercise intolerance, and muscle cramping. This high proportion of asymptomatic cases suggests both that these mutations may be associated with a mild phenotype and that caveolinopathy may be an underdiagnosed disease.Conclusion: This study extends our understanding of caveolinopathy; in particular, the findings suggest the need to consider caveolinopathy in patients with incidental findings of CK elevation. NGS may be a useful method in the differential diagnosis of such cases.