Genetic Testing

 What genes are known to cause HHT?

There are three 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. 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 ENGACVRL1 (ALK1), and SMAD4 genes. Depending on the lab used, results may take 4-10 weeks and will be communicated directly to the ordering physician and/or genetic counselor. The first person in the family to have genetic testing should be someone with a clinical diagnosis of HHT. The person will have comprehensive testing of the ENG,  ACVRL1 (ALK1) and SMAD4 genes, which includes full sequencing and deletion/duplication testing. If the mutation is identified, others in the family can have a much simpler test to target for the specific mutation.

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 mutation 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 mutation cannot be identified, at risk relatives, such as children or siblings, should have medical screening for AVMs.

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.

Please contact our UNC HHT Center Genetics Counselor for more information at 919-843-0827.

Genetic Testing Webinar         Ofri Leitner  MS, CGC

Nov 25, 2014