Genetic Testing

What genes are known to cause HHT?

There are four genes that are known to be associated with HHT. The first two, ENG and ACVRL1 (ALK1) lead to classical HHT. The third gene SMAD4 causes juvenile polyps to develop in the colon as well as symptoms of HHT. Pathogenic (harmful) genetic changes in the GDF2 gene are also associated with HHT but are less common. Two other genes, EPHB4 and RASA1, are associated with HHT-like syndromes. It is estimated that a genetic alteration (mutation) will be detected in ENG or ACVRL1 (ALK1) genes in about 85% of individuals who meet the Curacao clinical criteria.

Genetic testing involves sending a sample of blood to a specialized laboratory who will then analyze the abovementioned genes. Results usually take 2-3 weeks and will be communicated directly to the ordering physician and genetic counselor and will then be disclosed to the patient. The first person in the family to have genetic testing should be someone with a clinical diagnosis of HHT. This individual should have genetic testing for all of the known genes associated with HHT and HHT-like syndromes. This includes full sequencing and deletion/duplication analysis of the genes. If a harmful variant is identified, others in the family can have a much simpler test to target for the specific genetic change found in the affected individual.

Is it possible to have HHT but have genetic testing be normal?

Yes. In about 15% of individuals who have the signs and symptoms of HHT, a harmful genetic change will not be identified by genetic testing. This could be due to limitations of current technology or the existence of other, yet unidentified, genes that cause HHT. In families with HHT where a genetic cause cannot be identified, at risk relatives, such as children or siblings, should have medical screening for AVMs.

What is the risk to my children if I have HHT?

We all have two copies of every gene, with one copy being inherited from our mother and one from our father. When an individual carries a mutation in one of the inherited HHT genes, there is a 50% (1 in 2) chance that they pass on the altered gene to their children, and a 50% (1 in 2) chance they pass on the normal, working copy of the gene. Genes cannot skip generations, so if a person does not inherit a gene mutation, they cannot pass it to their children. Sometimes, HHT can occur as a new change in the family, and there may not be a family history of the condition. HHT has high age-related penetrance with variable expressivity, meaning symptoms can differ even among individuals in the same family.

Will my insurance pay for genetic testing?

Most insurance companies will cover genetic testing for HHT but it depends on the insurance provider and your specific plan. It would be advisable to call your insurance company if you have questions about coverage. Genetic testing has become significantly more affordable, and genetic testing laboratories have payment plans as well as financial assistance options to help alleviate the cost of the testing. This will be discussed by your genetic counselor during your visit at the HHT clinic.

Please contact our UNC HHT Center Genetic Counselor Zahra Girnary for more information at 919-966-0901.