Mild form of Danon disease: two case reports

Area of Science:

• Genetics
• Cardiology
• Neurology

Background:

• Danon disease is a rare genetic disorder.
• Typically presents with severe cardiomyopathy and early mortality in males.
• Caused by mutations in the lysosome-associated membrane protein-2 (LAMP-2) gene.

Observation:

• Two unrelated male patients presented with mild Danon disease manifestations.
• One patient, aged 39, showed progressive muscle weakness, borderline intelligence, and early retinopathy.
• A 53-year-old patient had asymptomatic extrasystoles, muscle weakness, and retinopathy, with no intellectual disability.

Findings:

• Both patients harbored the same hemizygous mutation (c.1097_1098delAA) in exon 9b of the LAMP-2 gene.
• Muscle pathology revealed autophagic vacuoles with sarcolemmal features.
• Cardiac evaluation showed asymptomatic mild left ventricular hypertrophy in one patient.

Implications:

• Mutations in LAMP-2 exon 9b may be associated with a milder form of Danon disease.
• This suggests genotype-phenotype correlations within Danon disease.
• Highlights the importance of genetic testing for diagnosing atypical presentations.