Hereditary Hemorrhagic Telangiectasia (HHT) is a genetic disorder of blood vessels, associated with small arteriovenous malformations (AVM) (telangiectases) of the skin, nose, and GI tract, and larger AVMs of the brain, lung or liver. Between 50,000 and 100,000 Americans are affected by HHT and most go undiagnosed. The majority of cases of HHT are due to pathogenic variants (mutations) in the endoglin gene (type 1), the ACVRL1 gene (type 2), and smaller percentage in the SMAD4 gene (HHT-juvenile polyposis syndrome). All of these genes encode proteins that are involved in the proper development of blood vessels. Clinical genetic testing for HHT is available. HHT has variable expression in each affected member of a family. This is analogous to fingerprints, i.e. each patient in a family has their own “fingerprint” (phenotype) despite having the same family HHT variant.
Nosebleeds, ranging from mild to severe, are the most common symptom of HHT, and can lead to iron deficiency anemia. Ischemic stroke, TIA (transient ischemic attack or “mini-stroke”), and brain abscess, due to pulmonary arteriovenous malformation (PAVM) and hemorrhagic stroke and seizure due to cerebral arteriovenous malformation (CAVM) can also occur. Gastrointestinal bleeding can be a problem in adults with HHT and a smaller number of patients with HHT are affected by significant liver malformations, which can cause symptoms such as heart failure, abdominal pain and abnormal liver function tests (biliary type), or symptoms similar to cirrhosis.
A common scenario in a family with undiagnosed HHT is the occurrence of a stroke or brain abscess that is treated without identifying the underlying cause of the problem. In these situations, when the PAVM/CAVM or its connection with HHT is not identified, the implications of the underlying disorder are not known to family members and as a result affected relatives may also develop sudden catastrophic events instead of receiving counseling, screening, and treatment before complications occur. Such “events” are preventable by early diagnosis, treatment and follow-up. Many patients are largely asymptomatic before their first serious complication.
Up to a half of patients with HHT have an AVM of the brain, lung, or liver, or HHT related gastrointestinal bleeding, which will require therapy by a team of physicians with expertise in this disorder. This, as well as the management of HHT related nosebleeds, are best done at an HHT Center of Excellence. HHT Centers are listed at www.curehht.org.