There are different types of HHT; HHT-1 and HHT-2 are most common. HHT-1 is a more serious form of the disease than HHT-2, because HHT-1 is often associated with vascular abnormalities of the lungs and the brains and because the nosebleeds usually start at a younger age.
HHT is caused by the shortage specific proteins which help stabilize blood vessel walls: "endoglin" or "activin-receptorlike-kinase-I (ALK-1)".
HHT-1 and HHT-2
The deficiency in endoglin of the vascular wall usually leads to a more serious form of the disease (HHT type 1) than a deficiency in ALK-1 (HHT type 2). In HHT type 1, we more often find abnormal blood vessels in the lung (48%) than in HHT type 2 (5%). Brain abnormalities also occur more often in HHT type 1 (15%) than in HHT type 2 (± 1%). The nose bleeds start at a younger age in HHT type 1, but they are no more severe than in HHT type 2. Vascular abnormalities of the liver, on the other hand, occur more often in HHT type 2.
More uncommon types of HHT
Not all patients have HHT type 1 or HHT type 2. A small number has HHT type 3 or HHT type 4; the affected genes are located on chromosomes 5 and 7, but the precise location is not yet known. Finally there is a very rare form of HHT associated with juvenile polyps in the colon. This is caused by mutations of MADH-4 on chromosome 18.
Although HHT type 1 is generally more severe than HHT type 2, there are other factors that influence the severity of the disease. We know that there is a considerable variation in the expression of the disease between families with HHT-1 or HHT-2, and even between members of the same family. A father might have only nose bleeds, whereas his child may have severe abnormalities in the lungs.
Studies on the life expectancy of HHT patients are being conducted. Previously published data on parents of our current HHT population (of which the majority was unscreened and untreated) show patients with type 1 HHT have a slightly shorter life-expectancy than patients without HHT or HHT type 2, especially women. We are analysing data on life-expectancy of our current HHT population and expect this to be published in 2017.