Newly Diagnosed Danon Disease is a rare, genetic condition

What does this mean for me and my family?

Danon Disease is caused by a mutation or deletion of the LAMP2 gene located on the X chromosome can be inherited (or passed down) from parents to their children. If someone in your family is diagnosed with Danon Disease, you may have questions about genetic testing for additional members in your family.

Genetic Considerations

X-Linked Dominant, Affected Mother

Danon is often (but not always) passed down through the mother. A mother with Danon will usually have one X chromosome with Danon and one X chromosome that is unaffected. This means she will pass down the affected chromosome that causes Danon in her children approximately half the time.

X-Linked Dominant, Affected Father

Fathers pass down either an X or Y chromosome that determines the sex of a child. Therefore, a father with Danon will pass down the affected X chromosome to his daughter 100% of the time, but not to a son who would get a Y chromosome (that does not impact Danon) from the father and an X chromosome from the mother.

‘De novo’ Mutation

There are times when Danon is not passed down by a parent, but rather, happens through a spontaneous mutation in the child’s genome, also know as a ‘de novo’ mutation.

Differences in Males and Females with Danon

Danon Disease is said to be X-linked because it is caused by genetic mutations or deletions on the X chromosome. Males have one X chromosome and one Y chromosome (XY), compared to females who have two X chromosomes (XX)

Danon in Males

Typically, males with the LAMP2 mutation or deletion will show more severe symptoms and develop symptoms at a younger age. A LAMP2 genetic mutation or deletion on the X chromosome in males will result in insufficient amounts of the LAMP2 protein or, in some cases, none at all.

Danon in Females

Females, on the other hand, have two X chromosomes. If a female has a mutation for Danon on one X chromosome, the other X chromosome may still produce enough of the LAMP2 protein for the body to function and compensate for the defect or “silence” the affected gene (this process can also be referred to as x-inactivation). As a result, females may present with greater variability of disease, ranging from having no signs or symptoms to being severely affected. Females may also develop symptoms earlier at a young age, later in life, or in some cases, be asymptomatic.

Genetic Testing

We recommend that you meet with a genetic counselor to discuss the most appropriate genetic test for you and/or your family members. Genetic counselors are healthcare professionals who assist in interpreting and understanding genetic test results. They can play a crucial role in helping people understand the implications of these results for their health and well-being.

Here are a few types of genetic tests:

Targeted or single-gene testing

Single-gene tests look for changes in only one gene.

Panel testing

A panel genetic test will look for changes in many genes rather than just one. These tests are usually grouped into categories for different kinds of medical concerns. A panel test will look at a group of genes associated with a higher risk of developing the disease in question.

Large-scale genetic or genomic testing

Large-scale genetic tests usually look at large sections of DNA or a person’s entire DNA.

Cascade testing

A process that involves testing family members for genetic conditions after one family member has been diagnosed. This testing offers one way to find people with genetic conditions before they show symptoms, allowing them to take steps to prevent

There are generally three outcomes from a genetic test: positive, negative, or inconclusive.

Positive

A positive test result will indicate that the individual has the genetic mutation or deletion

Negative

A negative test result means the individual does not the genetic mutation or deletion

Inconclusion

An inconclusive test result means there isn’t enough information to determine whether the individual does or does not have the disease. These results may also be reported as “uncertain.”

It is important for you to review your genetic testing results with a genetic counselor to interpret the information and also understand the implications for you and your family.

Additional Resources

For more information about genetic testing, visit the Genetic Cardiomyopathy Awareness Consortium.