Recommendations and guidance on the diagnosis and management of Danon disease

Abstract

ABSTRACT Introduction: Danon disease (DD) is a rare X-linked dominant cardioskeletal myopathy where phenotypic expression varies by sex. It is characterized by severe cardiomyopathy, skeletal myopathy, and cognitive impairment, but can include retinopathy, gastrointestinal, hepatic and pulmonary manifestations. Areas covered: This review of DD will cover genetics, pathophysiologic mechanisms, clinical characteristics and diagnostics, and management, and synthesizes Danon Disease literature found In PubMed from 2000 to the present. Clinical reviews, outcomes studies, registry data, case series and mechanistic studies and chapters were reviewed. Expert opinion: DD is caused by mutations in the lysosome-associated membrane protein-2 (LAMP-2) gene which is involved in autophagy. Diagnosis is aided by an x-linked hereditary pattern coupled with clinical history suggesting a cardiomyopathy with multi-organ dysfunction, neurocognitive deficits, myopathy and visual defects. Current treatment trials in DD are lacking and therapeutic decisions are extrapolated from guidelines for hypertrophic and dilated cardiomyopathies. The efficacy of these treatments as well as therapies specific to DD are important areas for research. Natural history studies that can inform therapeutic trial design as well as comparative effectiveness research specific to DD and other cardiomyopathies can bridge critical knowledge gaps in DD therapies.