Which are the causes of Hereditary Hemorrhagic Telangiectasia?

Hereditary Hemorrhagic Telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a rare genetic disorder that affects the blood vessels. It is characterized by the development of abnormal blood vessels called telangiectasias, which are fragile and prone to bleeding. These abnormal blood vessels can occur in various organs of the body, including the nose, skin, lungs, liver, and brain.

HHT is primarily caused by mutations in certain genes that are involved in the development and maintenance of blood vessels. The most commonly affected genes are Endoglin (ENG) and Activin A receptor type II-like kinase 1 (ACVRL1), also known as ALK1. These genes are responsible for producing proteins that regulate the growth and stability of blood vessels.

Hereditary Hemorrhagic Telangiectasia is inherited in an autosomal dominant manner, which means that a person only needs to inherit one copy of the mutated gene from either parent to develop the condition. If a parent has HHT, there is a 50% chance of passing the gene mutation to each of their children.

The specific genetic mutations in HHT lead to abnormal blood vessel formation and function. The loss or dysfunction of the proteins encoded by the ENG and ACVRL1 genes disrupts the signaling pathways involved in blood vessel development and maintenance. This results in the formation of fragile, dilated blood vessels that are prone to bleeding and can cause various symptoms.

While the exact mechanisms are not fully understood, several factors contribute to the development of HHT symptoms. One of the key factors is the abnormal blood vessel structure, which leads to the formation of telangiectasias. These telangiectasias are fragile and can rupture, causing recurrent nosebleeds (epistaxis), which is one of the most common symptoms of HHT.

Another important factor is the abnormal blood vessel connections that can occur in HHT. These abnormal connections, known as arteriovenous malformations (AVMs), can bypass the normal capillary network and result in direct connections between arteries and veins. AVMs can occur in various organs, including the lungs, liver, and brain. The presence of AVMs can lead to complications such as bleeding, organ dysfunction, and stroke.

Additionally, HHT can cause a disruption in the normal blood clotting process. The fragile blood vessels and abnormal blood flow patterns associated with the condition can impair the body's ability to form blood clots, leading to an increased risk of bleeding.

It is important to note that the severity and specific symptoms of HHT can vary widely among affected individuals. Some individuals may experience mild symptoms, while others may have more severe complications. The age of onset can also vary, with some individuals developing symptoms in childhood, while others may not experience symptoms until adulthood.

In conclusion, Hereditary Hemorrhagic Telangiectasia is primarily caused by genetic mutations in genes involved in blood vessel development and maintenance. These mutations lead to the formation of abnormal blood vessels and connections, as well as disruptions in the blood clotting process. The specific symptoms and severity of HHT can vary among individuals, highlighting the complex nature of this genetic disorder.