Danon disease as an underrecognized cause of hypertrophic cardiomyopathy in children

Zhao Yang, Colin J. McMahon, Liana R. Smith, Jeathrina Bersola, Adekunle M. Adesina, John P. Breinholt, Debra L. Kearney, William J. Dreyer, Susan W. Denfield, Jack F. Price, Michelle Grenier, Naomi J. Kertesz, Sarah K. Clunie, Susan D. Fernbach, James F. Southern, Stuart Berger, Jeffrey A. Towbin, Karla R. Bowles, Neil E. Bowles

Research output: Contribution to journalArticlepeer-review

144 Scopus citations


Background - Some patients with hypertrophic cardiomyopathy (HCM) or left ventricular hypertrophy also present with skeletal myopathy and Wolff-Parkinson-White (WPW) syndrome; mutations in the gene encoding the lysosome-associated protein-2 (LAMP-2) have been identified in these patients, suggesting that some of these patients have Danon disease. In this study we investigated the frequency of LAMP2 mutations in an unselected pediatric HCM population. Methods and Results - LAMP2 was amplified from genomic DNA isolated from peripheral lymphocytes of 50 patients diagnosed with HCM and analyzed by direct DNA sequencing. In 2 of the 50 probands (4%), nonsense mutations were identified. In 1 family the proband initially presented with HCM as a teenager, which progressed to dilated cardiomyopathy (DCM) and heart failure. Skeletal myopathy and WPW were also noted. The teenage sister of the proband is a carrier of the same LAMP2 mutation and has HCM without skeletal myopathy or WPW. The other proband presented with HCM, WPW, and skeletal myopathy as a teenager, whereas his carrier mother developed DCM during her 40s. Skeletal and cardiac muscle sections revealed the absence of LAMP-2 on immunohistochemical staining. Conclusions - LAMP2 mutations may account for a significant proportion of cases of HCM in children, especially when skeletal myopathy and/or WPW is present, suggesting that Danon disease is an underrecognized entity in the pediatric cardiology community.

Original languageEnglish (US)
Pages (from-to)1612-1617
Number of pages6
Issue number11
StatePublished - Sep 13 2005

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


Dive into the research topics of 'Danon disease as an underrecognized cause of hypertrophic cardiomyopathy in children'. Together they form a unique fingerprint.

Cite this