Danon disease presenting with dilated cardiomyopathy and a complex phenotype

J Hum Genet. 2007;52(10):830-835. doi: 10.1007/s10038-007-0184-8.


X-linked dilated cardiomyopathy (XLCM) was first described in 1987 and associated with dystrophin gene (DMD) mutations a decade later in one of the original two families. Here we report long-term follow-up of the second family (XLCM-2), for which a DMD mutation was never found. Analysis of the lysosome-associated membrane protein-2 (LAMP-2) gene detected a novel mutation, confirming a diagnosis of Danon disease. The broad phenotype in this family included dilated and hypertrophic cardiomyopathy, cardiac pre-excitation, skeletal myopathy with high serum creatinine kinase, cognitive impairement (in males), and and a pigmentary retinopathy in affected females. Cardiac biopsy in a 13-month-old mutation-carrying male showed no vacuolization by standard histology. We conclude that XLCM may be the presenting sign of Danon disease and, in the presence of familial history of HCM, pre-excitation, skeletal muscle involvement and retinal pigmentary dystrophy should prompt LAMP-2 clinical testing. Furthermore, the absence of vacuolar myopathy in biopsies from young patients may not exclude Danon disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cardiomyopathy, Dilated / diagnosis*
  • Cardiomyopathy, Dilated / genetics*
  • Cardiomyopathy, Dilated / pathology
  • Female
  • Glycogen Storage Disease Type IIb / diagnosis*
  • Glycogen Storage Disease Type IIb / genetics*
  • Glycogen Storage Disease Type IIb / pathology
  • Humans
  • Infant
  • Lysosomal Membrane Proteins / genetics*
  • Lysosomal-Associated Membrane Protein 2
  • Male
  • Middle Aged
  • Mutation
  • Pedigree
  • Phenotype


  • LAMP2 protein, human
  • Lysosomal-Associated Membrane Protein 2
  • Lysosomal Membrane Proteins