Natural history of Danon disease.

Abstract

BACKGROUND:

Danon disease is a rare but serious cardiac and skeletal myopathy leading to substantial morbidity and early mortality due to arrhythmia and cardiomyopathy. The X-linked nature of inheritance accounts for reported differences in phenotypic severity between men and women. The rarity of Danon disease has limited understanding of the complete phenotype. Clinical estimates of ages of disease onset and survival based on gender have not been published.

METHODS AND RESULTS:

We present data on 82 patients with Danon disease from 36 families, the largest series to date. Men were severely affected with cognitive disabilities (100%), hypertrophic cardiomyopathy (88%), and muscle weakness (80%). Men had a high morbidity and were unlikely to reach the age of 25 years without a cardiac transplantation. Women were less severely affected but reported higher than expected levels of cognitive (47%) and skeletal muscle complaints (50%) and manifesting an equal prevalence of dilated cardiomyopathy and hypertrophic cardiomyopathy. Combining our data with that of 63 other Danon disease case reports in the literature, the average ages of first symptom, cardiac transplantation, and death were 12.1, 17.9, and 19.0 years in men and 27.9, 33.7, and 34.6 years in women, respectively.

CONCLUSION:

These data more broadly illuminate the Danon disease phenotype and should prove useful to physicians working with and providing genetic counseling to families with Danon disease. Women with Danon disease present with clinical symptoms and events approximately 15 years after men and report a higher proportion of cognitive and skeletal muscle problems than previously recognized.

• Authors: Dana Boucek, Jean Jirikowic, Matthew Taylor
• Journal: Genetics in medicine : official journal of the American College of Medical Genetics (Genet Med) Vol. 13 Issue 6 Pg. 563-8 (Jun 2011) ISSN: 1530-0366 [Electronic] United States
• PMID: 21415759 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• LAMP2 protein, human
• Lysosomal-Associated Membrane Protein 2
• Lysosome-Associated Membrane Glycoproteins

Topics

• Adolescent
• Adult
• Child
• Child, Preschool
• Female
• Genetic Counseling
• Glycogen Storage Disease Type IIb (diagnosis, epidemiology, genetics)
• Humans
• Lysosomal-Associated Membrane Protein 2
• Lysosome-Associated Membrane Glycoproteins (genetics)
• Male
• Muscle Weakness (diagnosis)
• Phenotype
• Sex Factors