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DiseaseID HGD45
Genetic Disorder Hereditary Hemorrhagic Telangiectasia (HHT)
Gene Name endoglin(ENG) gene and activin-like kinase 1(ALK1) gene
Description

Hereditary Hemorrhagic Telangiectasia (HHT) is a genetic disorder of the blood vessels, which affects approximately 1 in 5,000 people. It affects males and females from all racial and ethnic groups. The disorder is also sometimes referred to as Osler-Weber-Rendu (OWR) after several doctors who studied HHT about 100 years ago. In 1896 Dr. Rendu first described HHT as a hereditary disorder involving nosebleeds and characteristic red spots that was distinctly different from hemophilia. HHT causes abnormalities of blood vessels. Most blood vessels in the body of someone with HHT are normal. However, a small percentage of the blood vessels in a person with HHT have a specific type of abnormality.Blood vessels are the tubes that carry blood around our bodies. There are two types of blood vessels: arteries and veins. Arteries carry blood under high pressure out to all areas of the body after being pumped by the heart. Veins carry blood that should be under low pressure, back to the heart. An artery does not usually connect directly to a vein. Usually there are very small blood vessels called capillaries that connect an artery to a vein. A person with HHT has a tendency to form blood vessels that lack the capillaries between an artery and vein. This means that arterial blood under high pressure flows directly into a vein without first having to squeeze through the very small capillaries. This place where an artery is connected directly to a vein tends to be a fragile site that can rupture and result in bleeding. We usually call a blood vessel that is abnormal in this way a telangiectasia (tel-AN-jee-eck-TAZE-ee-ya), if it involves small blood vessels. We tend to call it an arteriovenous malformation (AVM) if involves larger blood vessels. So, an AVM might be thought of as a big telangiectasia. The basic abnormality in the blood vessel is the same. Telangiectases tend to occur at the surface of the body such as the skin and the mucous membrane that lines the nose. AVMs tend to occur in the internal organs of the body. The telangiectases (plural for telangiectasia) and AVMs of HHT occur primarily in the nose, skin of the face, hands, and mouth and the lining of the stomach and intestines (GI tract), lungs, liver and brain. It is not currently known why these abnormal blood vessels tend to occur in certain parts of the body and not others. Hereditary Hemorrhagic Telangiectasia (HHT) is a genetic disorder of the blood vessels, which affects approximately 1 in 5,000 people. It affects males and females from all racial and ethnic groups. The disorder is also sometimes referred to as Osler-Weber-Rendu (OWR) after several doctors who studied HHT about 100 years ago. In 1896 Dr. Rendu first described HHT as a hereditary disorder involving nosebleeds and characteristic red spots that was distinctly different from hemophilia. HHT causes abnormalities of blood vessels. Most blood vessels in the body of someone with HHT are normal. However, a small percentage of the blood vessels in a person with HHT have a specific type of abnormality.Blood vessels are the tubes that carry blood around our bodies. There are two types of blood vessels: arteries and veins. Arteries carry blood under high pressure out to all areas of the body after being pumped by the heart. Veins carry blood that should be under low pressure, back to the heart. An artery does not usually connect directly to a vein. Usually there are very small blood vessels called capillaries that connect an artery to a vein. A person with HHT has a tendency to form blood vessels that lack the capillaries between an artery and vein. This means that arterial blood under high pressure flows directly into a vein without first having to squeeze through the very small capillaries. This place where an artery is connected directly to a vein tends to be a fragile site that can rupture and result in bleeding. We usually call a blood vessel that is abnormal in this way a telangiectasia (tel-AN-jee-eck-TAZE-ee-ya), if it involves small blood vessels. We tend to call it an arteriovenous malformation (AVM) if involves larger blood vessels. So, an AVM might be thought of as a big telangiectasia. The basic abnormality in the blood vessel is the same. Telangiectases tend to occur at the surface of the body such as the skin and the mucous membrane that lines the nose. AVMs tend to occur in the internal organs of the body. The telangiectases (plural for telangiectasia) and AVMs of HHT occur primarily in the nose, skin of the face, hands, and mouth and the lining of the stomach and intestines (GI tract), lungs, liver and brain. It is not currently known why these abnormal blood vessels tend to occur in certain parts of the body and not others. Hereditary Hemorrhagic Telangiectasia (HHT) is a genetic disorder of the blood vessels, which affects approximately 1 in 5,000 people. It affects males and females from all racial and ethnic groups. The disorder is also sometimes referred to as Osler-Weber-Rendu (OWR) after several doctors who studied HHT about 100 years ago. In 1896 Dr. Rendu first described HHT as a hereditary disorder involving nosebleeds and characteristic red spots that was distinctly different from hemophilia. HHT causes abnormalities of blood vessels. Most blood vessels in the body of someone with HHT are normal. However, a small percentage of the blood vessels in a person with HHT have a specific type of abnormality.Blood vessels are the tubes that carry blood around our bodies. There are two types of blood vessels: arteries and veins. Arteries carry blood under high pressure out to all areas of the body after being pumped by the heart. Veins carry blood that should be under low pressure, back to the heart. An artery does not usually connect directly to a vein. Usually there are very small blood vessels called capillaries that connect an artery to a vein. A person with HHT has a tendency to form blood vessels that lack the capillaries between an artery and vein. This means that arterial blood under high pressure flows directly into a vein without first having to squeeze through the very small capillaries. This place where an artery is connected directly to a vein tends to be a fragile site that can rupture and result in bleeding. We usually call a blood vessel that is abnormal in this way a telangiectasia (tel-AN-jee-eck-TAZE-ee-ya), if it involves small blood vessels. We tend to call it an arteriovenous malformation (AVM) if involves larger blood vessels. So, an AVM might be thought of as a big telangiectasia. The basic abnormality in the blood vessel is the same. Telangiectases tend to occur at the surface of the body such as the skin and the mucous membrane that lines the nose. AVMs tend to occur in the internal organs of the body. The telangiectases (plural for telangiectasia) and AVMs of HHT occur primarily in the nose, skin of the face, hands, and mouth and the lining of the stomach and intestines (GI tract), lungs, liver and brain. It is not currently known why these abnormal blood vessels tend to occur in certain parts of the body and not others. Hereditary Hemorrhagic Telangiectasia (HHT) is a genetic disorder of the blood vessels, which affects approximately 1 in 5,000 people. It affects males and females from all racial and ethnic groups. The disorder is also sometimes referred to as Osler-Weber-Rendu (OWR) after several doctors who studied HHT about 100 years ago. In 1896 Dr. Rendu first described HHT as a hereditary disorder involving nosebleeds and characteristic red spots that was distinctly different from hemophilia. HHT causes abnormalities of blood vessels. Most blood vessels in the body of someone with HHT are normal. However, a small percentage of the blood vessels in a person with HHT have a specific type of abnormality.Blood vessels are the tubes that carry blood around our bodies. There are two types of blood vessels: arteries and veins. Arteries carry blood under high pressure out to all areas of the body after being pumped by the heart. Veins carry blood that should be under low pressure, back to the heart. An artery does not usually connect directly to a vein. Usually there are very small blood vessels called capillaries that connect an artery to a vein. A person with HHT has a tendency to form blood vessels that lack the capillaries between an artery and vein. This means that arterial blood under high pressure flows directly into a vein without first having to squeeze through the very small capillaries. This place where an artery is connected directly to a vein tends to be a fragile site that can rupture and result in bleeding. We usually call a blood vessel that is abnormal in this way a telangiectasia (tel-AN-jee-eck-TAZE-ee-ya), if it involves small blood vessels. We tend to call it an arteriovenous malformation (AVM) if involves larger blood vessels. So, an AVM might be thought of as a big telangiectasia. The basic abnormality in the blood vessel is the same. Telangiectases tend to occur at the surface of the body such as the skin and the mucous membrane that lines the nose. AVMs tend to occur in the internal organs of the body. The telangiectases (plural for telangiectasia) and AVMs of HHT occur primarily in the nose, skin of the face, hands, and mouth and the lining of the stomach and intestines (GI tract), lungs, liver and brain. It is not currently known why these abnormal blood vessels tend to occur in certain parts of the body and not others. Hereditary Hemorrhagic Telangiectasia (HHT) is a genetic disorder of the blood vessels, which affects approximately 1 in 5,000 people. It affects males and females from all racial and ethnic groups. The disorder is also sometimes referred to as Osler-Weber-Rendu (OWR) after several doctors who studied HHT about 100 years ago. In 1896 Dr. Rendu first described HHT as a hereditary disorder involving nosebleeds and characteristic red spots that was distinctly different from hemophilia. HHT causes abnormalities of blood vessels. Most blood vessels in the body of someone with HHT are normal. However, a small percentage of the blood vessels in a person with HHT have a specific type of abnormality.Blood vessels are the tubes that carry blood around our bodies. There are two types of blood vessels: arteries and veins. Arteries carry blood under high pressure out to all areas of the body after being pumped by the heart. Veins carry blood that should be under low pressure, back to the heart. An artery does not usually connect directly to a vein. Usually there are very small blood vessels called capillaries that connect an artery to a vein. A person with HHT has a tendency to form blood vessels that lack the capillaries between an artery and vein. This means that arterial blood under high pressure flows directly into a vein without first having to squeeze through the very small capillaries. This place where an artery is connected directly to a vein tends to be a fragile site that can rupture and result in bleeding. We usually call a blood vessel that is abnormal in this way a telangiectasia (tel-AN-jee-eck-TAZE-ee-ya), if it involves small blood vessels. We tend to call it an arteriovenous malformation (AVM) if involves larger blood vessels. So, an AVM might be thought of as a big telangiectasia. The basic abnormality in the blood vessel is the same. Telangiectases tend to occur at the surface of the body such as the skin and the mucous membrane that lines the nose. AVMs tend to occur in the internal organs of the body. The telangiectases (plural for telangiectasia) and AVMs of HHT occur primarily in the nose, skin of the face, hands, and mouth and the lining of the stomach and intestines (GI tract), lungs, liver and brain. It is not currently known why these abnormal blood vessels tend to occur in certain parts of the body and not others. Hereditary Hemorrhagic Telangiectasia (HHT) is a genetic disorder of the blood vessels, which affects approximately 1 in 5,000 people. It affects males and females from all racial and ethnic groups. The disorder is also sometimes referred to as Osler-Weber-Rendu (OWR) after several doctors who studied HHT about 100 years ago. In 1896 Dr. Rendu first described HHT as a hereditary disorder involving nosebleeds and characteristic red spots that was distinctly different from hemophilia. HHT causes abnormalities of blood vessels. Most blood vessels in the body of someone with HHT are normal. However, a small percentage of the blood vessels in a person with HHT have a specific type of abnormality.Blood vessels are the tubes that carry blood around our bodies. There are two types of blood vessels: arteries and veins. Arteries carry blood under high pressure out to all areas of the body after being pumped by the heart. Veins carry blood that should be under low pressure, back to the heart. An artery does not usually connect directly to a vein. Usually there are very small blood vessels called capillaries that connect an artery to a vein. A person with HHT has a tendency to form blood vessels that lack the capillaries between an artery and vein. This means that arterial blood under high pressure flows directly into a vein without first having to squeeze through the very small capillaries. This place where an artery is connected directly to a vein tends to be a fragile site that can rupture and result in bleeding. We usually call a blood vessel that is abnormal in this way a telangiectasia (tel-AN-jee-eck-TAZE-ee-ya), if it involves small blood vessels. We tend to call it an arteriovenous malformation (AVM) if involves larger blood vessels. So, an AVM might be thought of as a big telangiectasia. The basic abnormality in the blood vessel is the same. Telangiectases tend to occur at the surface of the body such as the skin and the mucous membrane that lines the nose. AVMs tend to occur in the internal organs of the body. The telangiectases (plural for telangiectasia) and AVMs of HHT occur primarily in the nose, skin of the face, hands, and mouth and the lining of the stomach and intestines (GI tract), lungs, liver and brain. It is not currently known why these abnormal blood vessels tend to occur in certain parts of the body and not others. Hereditary Hemorrhagic Telangiectasia (HHT) is a genetic disorder of the blood vessels, which affects approximately 1 in 5,000 people. It affects males and females from all racial and ethnic groups. The disorder is also sometimes referred to as Osler-Weber-Rendu (OWR) after several doctors who studied HHT about 100 years ago. In 1896 Dr. Rendu first described HHT as a hereditary disorder involving nosebleeds and characteristic red spots that was distinctly different from hemophilia. HHT causes abnormalities of blood vessels. Most blood vessels in the body of someone with HHT are normal. However, a small percentage of the blood vessels in a person with HHT have a specific type of abnormality.Blood vessels are the tubes that carry blood around our bodies. There are two types of blood vessels: arteries and veins. Arteries carry blood under high pressure out to all areas of the body after being pumped by the heart. Veins carry blood that should be under low pressure, back to the heart. An artery does not usually connect directly to a vein. Usually there are very small blood vessels called capillaries that connect an artery to a vein. A person with HHT has a tendency to form blood vessels that lack the capillaries between an artery and vein. This means that arterial blood under high pressure flows directly into a vein without first having to squeeze through the very small capillaries. This place where an artery is connected directly to a vein tends to be a fragile site that can rupture and result in bleeding. We usually call a blood vessel that is abnormal in this way a telangiectasia (tel-AN-jee-eck-TAZE-ee-ya), if it involves small blood vessels. We tend to call it an arteriovenous malformation (AVM) if involves larger blood vessels. So, an AVM might be thought of as a big telangiectasia. The basic abnormality in the blood vessel is the same. Telangiectases tend to occur at the surface of the body such as the skin and the mucous membrane that lines the nose. AVMs tend to occur in the internal organs of the body. The telangiectases (plural for telangiectasia) and AVMs of HHT occur primarily in the nose, skin of the face, hands, and mouth and the lining of the stomach and intestines (GI tract), lungs, liver and brain. It is not currently known why these abnormal blood vessels tend to occur in certain parts of the body and not others. Hereditary Hemorrhagic Telangiectasia (HHT) is a genetic disorder of the blood vessels, which affects approximately 1 in 5,000 people. It affects males and females from all racial and ethnic groups. The disorder is also sometimes referred to as Osler-Weber-Rendu (OWR) after several doctors who studied HHT about 100 years ago. In 1896 Dr. Rendu first described HHT as a hereditary disorder involving nosebleeds and characteristic red spots that was distinctly different from hemophilia. HHT causes abnormalities of blood vessels. Most blood vessels in the body of someone with HHT are normal. However, a small percentage of the blood vessels in a person with HHT have a specific type of abnormality.Blood vessels are the tubes that carry blood around our bodies. There are two types of blood vessels: arteries and veins. Arteries carry blood under high pressure out to all areas of the body after being pumped by the heart. Veins carry blood that should be under low pressure, back to the heart. An artery does not usually connect directly to a vein. Usually there are very small blood vessels called capillaries that connect an artery to a vein. A person with HHT has a tendency to form blood vessels that lack the capillaries between an artery and vein. This means that arterial blood under high pressure flows directly into a vein without first having to squeeze through the very small capillaries. This place where an artery is connected directly to a vein tends to be a fragile site that can rupture and result in bleeding. We usually call a blood vessel that is abnormal in this way a telangiectasia (tel-AN-jee-eck-TAZE-ee-ya), if it involves small blood vessels. We tend to call it an arteriovenous malformation (AVM) if involves larger blood vessels. So, an AVM might be thought of as a big telangiectasia. The basic abnormality in the blood vessel is the same. Telangiectases tend to occur at the surface of the body such as the skin and the mucous membrane that lines the nose. AVMs tend to occur in the internal organs of the body. The telangiectases (plural for telangiectasia) and AVMs of HHT occur primarily in the nose, skin of the face, hands, and mouth and the lining of the stomach and intestines (GI tract), lungs, liver and brain. It is not currently known why these abnormal blood vessels tend to occur in certain parts of the body and not others. Hereditary Hemorrhagic Telangiectasia (HHT) is a genetic disorder of the blood vessels, which affects approximately 1 in 5,000 people. It affects males and females from all racial and ethnic groups. The disorder is also sometimes referred to as Osler-Weber-Rendu (OWR) after several doctors who studied HHT about 100 years ago. In 1896 Dr. Rendu first described HHT as a hereditary disorder involving nosebleeds and characteristic red spots that was distinctly different from hemophilia. HHT causes abnormalities of blood vessels. Most blood vessels in the body of someone with HHT are normal. However, a small percentage of the blood vessels in a person with HHT have a specific type of abnormality.Blood vessels are the tubes that carry blood around our bodies. There are two types of blood vessels: arteries and veins. Arteries carry blood under high pressure out to all areas of the body after being pumped by the heart. Veins carry blood that should be under low pressure, back to the heart. An artery does not usually connect directly to a vein. Usually there are very small blood vessels called capillaries that connect an artery to a vein. A person with HHT has a tendency to form blood vessels that lack the capillaries between an artery and vein. This means that arterial blood under high pressure flows directly into a vein without first having to squeeze through the very small capillaries. This place where an artery is connected directly to a vein tends to be a fragile site that can rupture and result in bleeding. We usually call a blood vessel that is abnormal in this way a telangiectasia (tel-AN-jee-eck-TAZE-ee-ya), if it involves small blood vessels. We tend to call it an arteriovenous malformation (AVM) if involves larger blood vessels. So, an AVM might be thought of as a big telangiectasia. The basic abnormality in the blood vessel is the same. Telangiectases tend to occur at the surface of the body such as the skin and the mucous membrane that lines the nose. AVMs tend to occur in the internal organs of the body. The telangiectases (plural for telangiectasia) and AVMs of HHT occur primarily in the nose, skin of the face, hands, and mouth and the lining of the stomach and intestines (GI tract), lungs, liver and brain. It is not currently known why these abnormal blood vessels tend to occur in certain parts of the body and not others. Hereditary Hemorrhagic Telangiectasia (HHT) is a genetic disorder of the blood vessels, which affects approximately 1 in 5,000 people. It affects males and females from all racial and ethnic groups. The disorder is also sometimes referred to as Osler-Weber-Rendu (OWR) after several doctors who studied HHT about 100 years ago. In 1896 Dr. Rendu first described HHT as a hereditary disorder involving nosebleeds and characteristic red spots that was distinctly different from hemophilia. HHT causes abnormalities of blood vessels. Most blood vessels in the body of someone with HHT are normal. However, a small percentage of the blood vessels in a person with HHT have a specific type of abnormality.Blood vessels are the tubes that carry blood around our bodies. There are two types of blood vessels: arteries and veins. Arteries carry blood under high pressure out to all areas of the body after being pumped by the heart. Veins carry blood that should be under low pressure, back to the heart. An artery does not usually connect directly to a vein. Usually there are very small blood vessels called capillaries that connect an artery to a vein. A person with HHT has a tendency to form blood vessels that lack the capillaries between an artery and vein. This means that arterial blood under high pressure flows directly into a vein without first having to squeeze through the very small capillaries. This place where an artery is connected directly to a vein tends to be a fragile site that can rupture and result in bleeding. We usually call a blood vessel that is abnormal in this way a telangiectasia (tel-AN-jee-eck-TAZE-ee-ya), if it involves small blood vessels. We tend to call it an arteriovenous malformation (AVM) if involves larger blood vessels. So, an AVM might be thought of as a big telangiectasia. The basic abnormality in the blood vessel is the same. Telangiectases tend to occur at the surface of the body such as the skin and the mucous membrane that lines the nose. AVMs tend to occur in the internal organs of the body. The telangiectases (plural for telangiectasia) and AVMs of HHT occur primarily in the nose, skin of the face, hands, and mouth and the lining of the stomach and intestines (GI tract), lungs, liver and brain. It is not currently known why these abnormal blood vessels tend to occur in certain parts of the body and not others. Hereditary Hemorrhagic Telangiectasia (HHT) is a genetic disorder of the blood vessels, which affects approximately 1 in 5,000 people. It affects males and females from all racial and ethnic groups. The disorder is also sometimes referred to as Osler-Weber-Rendu (OWR) after several doctors who studied HHT about 100 years ago. In 1896 Dr. Rendu first described HHT as a hereditary disorder involving nosebleeds and characteristic red spots that was distinctly different from hemophilia. HHT causes abnormalities of blood vessels. Most blood vessels in the body of someone with HHT are normal. However, a small percentage of the blood vessels in a person with HHT have a specific type of abnormality.Blood vessels are the tubes that carry blood around our bodies. There are two types of blood vessels: arteries and veins. Arteries carry blood under high pressure out to all areas of the body after being pumped by the heart. Veins carry blood that should be under low pressure, back to the heart. An artery does not usually connect directly to a vein. Usually there are very small blood vessels called capillaries that connect an artery to a vein. A person with HHT has a tendency to form blood vessels that lack the capillaries between an artery and vein. This means that arterial blood under high pressure flows directly into a vein without first having to squeeze through the very small capillaries. This place where an artery is connected directly to a vein tends to be a fragile site that can rupture and result in bleeding. We usually call a blood vessel that is abnormal in this way a telangiectasia (tel-AN-jee-eck-TAZE-ee-ya), if it involves small blood vessels. We tend to call it an arteriovenous malformation (AVM) if involves larger blood vessels. So, an AVM might be thought of as a big telangiectasia. The basic abnormality in the blood vessel is the same. Telangiectases tend to occur at the surface of the body such as the skin and the mucous membrane that lines the nose. AVMs tend to occur in the internal organs of the body. The telangiectases (plural for telangiectasia) and AVMs of HHT occur primarily in the nose, skin of the face, hands, and mouth and the lining of the stomach and intestines (GI tract), lungs, liver and brain. It is not currently known why these abnormal blood vessels tend to occur in certain parts of the body and not others. Hereditary Hemorrhagic Telangiectasia (HHT) is a genetic disorder of the blood vessels, which affects approximately 1 in 5,000 people. It affects males and females from all racial and ethnic groups. The disorder is also sometimes referred to as Osler-Weber-Rendu (OWR) after several doctors who studied HHT about 100 years ago. In 1896 Dr. Rendu first described HHT as a hereditary disorder involving nosebleeds and characteristic red spots that was distinctly different from hemophilia. HHT causes abnormalities of blood vessels. Most blood vessels in the body of someone with HHT are normal. However, a small percentage of the blood vessels in a person with HHT have a specific type of abnormality.Blood vessels are the tubes that carry blood around our bodies. There are two types of blood vessels: arteries and veins. Arteries carry blood under high pressure out to all areas of the body after being pumped by the heart. Veins carry blood that should be under low pressure, back to the heart. An artery does not usually connect directly to a vein. Usually there are very small blood vessels called capillaries that connect an artery to a vein. A person with HHT has a tendency to form blood vessels that lack the capillaries between an artery and vein. This means that arterial blood under high pressure flows directly into a vein without first having to squeeze through the very small capillaries. This place where an artery is connected directly to a vein tends to be a fragile site that can rupture and result in bleeding. We usually call a blood vessel that is abnormal in this way a telangiectasia (tel-AN-jee-eck-TAZE-ee-ya), if it involves small blood vessels. We tend to call it an arteriovenous malformation (AVM) if involves larger blood vessels. So, an AVM might be thought of as a big telangiectasia. The basic abnormality in the blood vessel is the same. Telangiectases tend to occur at the surface of the body such as the skin and the mucous membrane that lines the nose. AVMs tend to occur in the internal organs of the body. The telangiectases (plural for telangiectasia) and AVMs of HHT occur primarily in the nose, skin of the face, hands, and mouth and the lining of the stomach and intestines (GI tract), lungs, liver and brain. It is not currently known why these abnormal blood vessels tend to occur in certain parts of the body and not others.

Symptoms

Causes An abnormal gene on either chromosome 9 or 12 causes most HHT. The gene on chromosome 9 is called endoglin and the gene on chromosome 12 is called activin-like kinase 1 (ALK-1). Any particular individual or family will have only one of these two genes appear abnormal. Normally, these genes produce a substance that is involved in the formation of blood vessels. Because of an abnormality in one of these genes, individuals with HHT make less of one of these substances. This, in turn, can interfere with the normal formation of a blood vessel. The abnormal HHT gene is usually inherited from one parent who has HHT. HHT is a “dominant” disorder, meaning it only takes one abnormal copy of the gene, from only one parent, to cause the disorder. Each child of a parent with an HHT gene has a 50% chance of inheriting this abnormal gene. If a particular child does not inherit the HHT gene from his or her parent, he/she has no chance to pass the HHT gene to a child or grandchild. The gene does not skip generations! However, sometimes it can appear to skip because an individual with an HHT gene has symptoms that are so mild that they aren?t recognized, or if recognized are not correctly attributed to HHT. Very rarely in HHT, a genetic accident (new mutation) occurs in a sperm or egg cell of an unaffected parent and causes HHT in the child. But in most cases, the abnormal HHT gene has been in the family for generations. Almost 10 years after the genes which cause the most common forms of HHT (HHT1 and HHT2) were discovered, a new gene was identified that causes a combined syndrome of HHT and juvenile polyposis. Juvenile polyposis is characterized by multiple polyps in the intestinal tract, usually noticed clinically at a young age. Patients with juvenile polyps are at risk for gastrointestinal cancer at much younger ages than GI cancer typically occurs. Mutations in a gene called MADH4 (or sometimes referred to as SMAD4) cause this combined syndrome. It is important to understand that most patients or families with HHT do not have polyposis. This is a distinct and separate medical condition that combines the clinical features of both disorders in the same family. Like HHT, it affects both males and females and can be passed from either a father or mother to their child. The fact that these two disorders (HHT and juvenile polyposis) occasionally go together as a “package” has implications for how physicians should manage patients with either one. First, anyone in an HHT family with gastrointestinal bleeding at an early age should be screened for mutations in the MADH4 gene. If a mutation in MADH4 is found, genetic testing should be offered to other family members at risk and screening for juvenile polyps should be performed on those people who have the mutation. Screening for juvenile polyps should also be performed in any individual with a history of gastrointestinal bleeding. Second, patients with juvenile polyposis and mutations in the MADH4 gene, or juvenile polyposis and a family history consistent with HHT, should be screened for the internal AVMs of HHT that can present unexpectedly and cause serious complications.
Diagnosis The diagnosis of HHT is considered definite if three or more of the following four criteria are present, or suspected if two of the following four criteria are present: Nosebleeds- spontaneous and recurrent Telangiectases- multiple, at characteristic sites, including lips, oral cavity, fingers and nose Internal telangiectases or AVM- lung, brain, GI, liver or spinal Family history-parent, sibling or child with HHT according to these criteria To establish the diagnosis of HHT in your family, and to proceed with genetic testing as needed it is usually best to be seen at an HHT Center, or a genetics clinic in your area. Physicians or genetic counselors in these clinics will understand the process and particulars of how best to determine whether you and/or members of your family have HHT, including genetic testing. The youngest individuals in an HHT family are typically the most helped by genetic testing, but testing usually must start with a parent or grandparent.
Treatment Although there is not yet a way to prevent the telangiectases or AVMs from occurring, most can be treated once they occur. They should be treated if they are either causing a significant problem (as in the case of frequent nosebleeds) or if they are at high risk of causing a serious problem (such as a stroke from a lung AVM.) The recommended treatment for a telangiectasia or AVM depends on both its size and location in the body. Bleeding from telangiectases in the nose sometimes responds satisfactorily to some everyday practical treatments implemented at home. Humidification of the air and use of an ointment on the lining of the nose help keep the mucous membrane of the nose moist and can reduce nosebleeds. There are products sold over-the-counter in pharmacies or pharmacy sections of big stores that can be used to help control nosebleeds when simple pressure applied to the outside of the nose isn?t enough. If these home management techniques do not result in a satisfactory control or reduction in nosebleeds, the first medical treatment that should usually be considered is laser therapy. Laser coagulation therapy is preferable to electric and chemical cautery primarily because- if done carefully by an ENT physician with specific expertise in both laser therapy and HHT - it has less risk to damage the inside of the nose. A small beam is directed around the margins of each telangiectasia and photocoagulation occurs. Most patients who undergo laser therapy see significant improvement for a period of time, but it usually needs to be repeat ed periodically. Because the procedure has little risk of harming the nose if done by an experienced physician, it can be repeated as needed. Septal dermoplasty is another treatment option for severe nosebleeds, and is usually considered when laser therapy has repeatedly failed to help. Septal dermoplasty replaces the thin lining of the nose (called the mucous membrane) with a thicker graft of skin. When performed by an ENT (Ears, Nose, and Throat) physician knowledgeable and experienced with the Saunder’s method, it can significantly reduce the frequency and severity of nosebleeds. It is a more drastic treatment than laser in that it permanently removes the natural lining of nose and replaces it with skin. Daily care and attention to the nose is required after septal dermoplasty to keep the nose moist and clean. Some studies have shown hormonal therapy to be helpful in some patients for whom the local therapies (i.e. home moisturizing care and laser therapy) have not been successful. Embolization (blocking off an artery) can be used to halt severe nose bleeding that has been unresponsive to other treatments, but is usually only effective for 6-8 weeks. Other arteries enlarge and cause recurrence of the bleeding. This therapy for the nose is generally used only on an emergency basis and is generally only a temporary measure. Telangiectases of the skin can also be treated with laser therapy if they bleed to an extent that is bothersome or if the telangiectases are a cosmetic concern. Lesions of the skin are usually best treated by a dermatologist who has particular expertise in the use of lasers. Bleeding from the stomach or intestines is generally treated only if it causes anemia (low blood count.) Iron replacement therapy is the first line of defense. Iron is usually first given orally (a tablet by mouth), but can be given intravenously (IV) if a patient does not tolerate the oral iron, or if the oral method is not getting enough iron into the body. If iron therapy cannot control the anemia, transfusion and endoscopic treatments using a heater probe, bicap, argon photocoagulation or laser are options. Hormonal treatment has also been helpful in some people. Lung and brain AVMs should be treated before they cause symptoms or problems in most cases. This is why testing or screening for them is recommended in all individuals with HHT, regardless of their specific symptoms. Lung AVMs can almost always be treated completely and permanently using an outpatient procedure called embolization. An Interventional Radiologist inserts a small tube (catheter) in a large vein in the groin. The tube is then passed through the blood vessel system to the AVM in the lung. A devise (a coil or occasionally a balloon) is placed in the artery leading to the AVM to stop blood flow through the AVM. The procedure usually takes 1-3 hours and requires only a few hours of recuperation. Brain AVMs are treated in different ways depending on the size, structure and location in the brain of the abnormal blood vessels. Surgery, embolization and stereotactic radiosurgery can all be used, separately or in combination, to successfully treat brain AVMs. Liver AVMs are currently treated only if a patient shows signs of liver or heart failure, as a result of their liver AVM. Embolization, which is so successful for the treatment of pulmonary AVMs, can cause severe complications when performed in the liver. Decisions regarding treatment of liver AVM are made on a case-by-case basis and should be managed by a physician very familiar with the liver manifestations of HHT.
     
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