In some patients, PH can be inherited from their parents. Patients with inherited PAH are said to have heritable PAH (HPAH).
- HPAH should be suspected when more than one closely related person in a family (parent, child, sibling) has PAH
- In a family with known HPAH, the risk to individuals is still quite small. On average, only 1 in 10 will develop PAH
- In patients thought to have idiopathic PAH (IPAH), up to 1 in 5 may actually have HPAH. Sometimes, a very detailed or careful medical history of a family can suggest HPAH
Patients with HPAH have a mutation (error) in the DNA code of 1 gene or a number of genes out of the roughly 30,000 genes on the human genome. These mutant genes are transmitted to a patient from her/his parents.
- The first mutant gene that causes HPAH was discovered in 2000. This gene is called BMP-R2 (bone morphogenetic protein receptor 2). The normal function of the BMP-R2gene is to allow cells to make a protein, called BMP-R2 protein. BMP-R2 protein helps the body control the behaviour of cells in the walls of pulmonary arteries, including endothelial cells and smooth muscle cells. In these cells, BMP-R2 controls:
- How these cells grow and multiply (also known as reproduce or proliferate)
- How these cells mature or change their function (also known as differentiate)
- When these cells should normally die to make room for other cells
- Another mutant gene that causes HPAH is ALK-1
Nevertheless, the mutation responsible for HPAH is only found in about 80% of patients with HPAH. This is likely because other mutations causing HPAH have not been discovered yet, although less common mutations have been documented in recent years.
It is important to realize that in most patients with PH (all types other than HPAH), there is no evidence that PH is inherited.