Condition Description

Danon Disease is anX-linked disorder that can affect cardiac muscle, skeletal muscle, and mentalretardation. Affected individuals have also been described with hypertrophiccardiomyopathy, proximal muscle weakness, hepatomegaly, peripheral pigmentaryretinopathy, and elevated creatine kinase. Presentation can be variable evenwithin a family. Affected individuals usually die in their teens or twentiesdue to heart failure; heart transplantation has been shown to be an effectivetreatment. Females have been reported to display symptoms of Danon disease, aswell. Symptoms reported in affected females include skeletal myopathy, atrialfibrillation, mild left ventricular enlargement with systolic dysfunction onechocardiogram, pigmentary retinopathy, mild intellectual impairment, mentalretardation, and death from cardiac disease. While cardiomyopathy in affectedmales occurs before the age of 20, most affected females develop cardiomyopathyin adulthood.

Mutations in the LAMP2 gene (Xq24) have been associatedwith Danon disease. One study reported that the prevalence of Danon disease was1% of patients with hypertrophic cardiomyopathy (2 of 197 patients). In thisstudy, Danon disease was responsible for 50% of the cases of hypertrophiccardiomyopathy (CMH) with clinical skeletal myopathy (2 of 4 patients); none ofthe 41 patients with isolated CMH had Danon disease. In another study, geneticanalyses of 24 subjects with increased left ventricular wall thickness andelectrocardiogram suggesting ventricular preexcitation found 4 LAMP2 mutations. Clinical featuresassociated with defects in LAMP2 included male sex, severe hypertrophy, early onset (at 8 to 17 years of age),ventricular preexcitation, and asymptomatic elevations of two serum proteins.Mutations in heterozygous state appeared to be responsible for unusual heartdisease in some females.

Although this disorderwas originally described as a variant of glycogen storage disease II due toaccumulation of glycogen in muscle and lysosomes seen in some patients, acidalpha-glucosidase and other enzymes of glycogen metabolism are normal. Glycogen,however, is not always increased in affected individuals. The subsequentidentification of the structural lysosome-associated membrane protein-2 gene asresponsible for the disorder enabled the proper identification of Danon diseaseas resulting from a defect of the lysosomal membrane.

For patients with suspected Danon disease, sequence analysis is recommended as the first step in mutation identification. For patients in whom mutations are not identified by full gene sequencing, deletion/duplication analysis is appropriate.

Click here for the OMIM summary on this condition.

Genes (1)


This test is indicated for:

  • Confirmation of a clinical/biochemical diagnosis of Danon disease
  • Carrier testing in adult females with a family history of Danon disease


PCR amplification of 9 exons contained in the LAMP2 gene is performed on the patient's genomic DNA. Direct sequencing of amplification products is performed in both forward and reverse directions, using automated fluorescence dideoxy sequencing methods. The patient's gene sequences are then compared to a normal reference sequence. Sequence variations are classified as mutations, benign variants unrelated to disease, or variations of unknown clinical significance. Variants of unknown clinical significance may require further studies of the patient and/or family members. This assay does not interrogate the promoter region, deep intronic regions, or other regulatory elements, and does not detect large deletions.


Clinical Sensitivity: Unknown. Mutations in the promoter region, some mutations in the introns and other regulatory element mutations cannot be detected by this analysis. Large deletions will not be detected by this analysis. Results of molecular analysis should be interpreted in the context of the patient's biochemical phenotype.

Analytical Sensitivity: ~99%

Specimen Requirements

Listed below are EGL's preferred sample criteria. For any questions, please call 470.378.2200 and ask to speak with a laboratory genetic counselor (
Submit only 1 of the following specimen types

Oragene™ Saliva Collection Kit
Orangene™ Saliva Collection Kit used according to manufacturer instructions. Please contact EGL for a Saliva Collection Kit for patients that cannot provide a blood sample.
Collection and Shipping
Please do not refrigerate or freeze saliva sample. Please store and ship at room temperature.
DNA, Isolated

Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Collection and Shipping
Refrigerate until time of shipment in 100 ng/µL in TE buffer. Ship sample at room temperature with overnight delivery.
Whole Blood (EDTA)

EDTA (Purple Top)
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Collection and Shipping
Ship sample at room temperature for receipt at EGL within 72 hours of collection. Do not freeze.

Special Instructions

Submit copies of diagnostic biochemical test results with the sample, if appropriate. Contact the laboratory if further information is needed.

Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed outside of EGL Genetics, please submit a copy of the sequencing report with the test requisition.

  • Deletion/duplication analysis of the LAMP2 gene by CGH array is available for those individuals in whom sequence analysis is negative (YE).
  • X-Linked Intellectual Disability panels are available for 30, 60, and 90+ genes.
  • Custom diagnostic mutation analysis (KM) is available to family members if mutations are identified by targeted mutation testing or sequencing analysis.
  • Prenatal testing is available to adult females who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.

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