Hereditary hemorrhagic telangiectasia is a hereditary disorder of vascular malformation transmitted as an autosomal dominant trait affecting men and women.
More than 80% of patients have mutations in the endoglin (ENG) gene, which encodes a receptor for transforming growth factor beta-1 (TGF-β1) and TGF-β3 or in the MADH4 gene, which encodes SMAD4, a protein active in the TGF-β signalling pathway.
Symptoms and Signs
The most characteristic lesions are small red-to-violet telangiectatic lesions on the face, lips, oral and nasal mucosa, and tips of the fingers and toes. Similar lesions may be present throughout the mucosa of the GI tract, resulting in recurrent GI bleeding. Patients may experience recurrent, profuse nosebleeds. Some patients have pulmonary arteriovenous fistulas. These fistulas may cause significant right-to-left shunts, which can result in dyspnea, fatigue, cyanosis, or polycythemia. However, the first sign of their presence may be a brain abscess, transient ischemic attack, or stroke as a result of infected or noninfected emboli. Cerebral or spinal arteriovenous malformations occur in some families and may cause subarachnoid hemorrhage, seizures, or paraplegia. Hepatic arteriovenous malformations may lead to liver failure and high output heart failure.
Diagnosis is based on the finding of characteristic arteriovenous malformations on the face, mouth, nose, and digits. Endoscopy or angiography is sometimes needed. Laboratory findings are usually normal except for iron deficiency anemia in many patients.
Testing for the ENG and SMAD4 mutations may be helpful in some patients with atypical features or for screening asymptomatic family members.
If a family history of pulmonary, hepatic, or cerebral arteriovenous malformations exists, screening at puberty and at the end of adolescence with pulmonary CT, hepatic CT, and cerebral MRI is recommended.
Treatment for most patients is supportive, but accessible telangiectasias (eg, in the nose or GI tract via endoscopy) may be treated with laser ablation. Arteriovenous fistulas may be treated by surgical resection or embolization. Repeated blood transfusions may be needed; therefore, immunization with hepatitis B vaccine is important. Many patients require continuous iron therapy to replace iron lost in repeated mucosal bleeding; many patients require parenteral iron and sometimes erythropoietin (see Iron Deficiency Anemia). Treatment with drugs that inhibit fibrinolysis, such as aminocaproic acid or tranexamic acid may be beneficial.
Last full review/revision September 2014 by David J. Kuter, MD, DPhil
Content last modified October 2014