International Consensus on Differential Diagnosis and Management of Patients With Danon Disease: JACC State-of-the-Art Review.

Danon disease is a rare X-linked autophagic vacuolar cardioskeletal myopathy associated with severe heart failure that can be accompanied with extracardiac neurologic, skeletal, and ophthalmologic manifestations. It is caused by loss of function variants in the LAMP2 gene and is among the most severe and penetrant of the genetic cardiomyopathies. Most patients with Danon disease will experience symptomatic heart failure. Male individuals generally present earlier than women and die of either heart failure or arrhythmia or receive a heart transplant by the third decade of life. Herein, the authors review the differential diagnosis of Danon disease, diagnostic criteria, natural history, management recommendations, and recent advances in treatment of this increasingly recognized and extremely morbid cardiomyopathy. [Display omitted] • Danon disease is a rare, X-linked genetic cardiomyopathy in which protein deficiency results in autophagy, accumulation of autophagosomes, defective mitochondria myocyte death, and adverse clinical outcomes. • Clinical features include myocardial hypertrophy, conduction abnormalities, heart failure, malignant ventricular arrhythmia, and multisystem involvement. • Understanding the pathophysiology and clinical trajectory of Danon disease may promote earlier diagnosis, risk stratification, and patient selection for medical and gene therapies that may have implications for other genetic cardiomyopathies. [ABSTRACT FROM AUTHOR]