Hereditary Telangiectasia

Autosomal dominant mucocutaneous and visceral fibrovascular dysplasia in which telangiectasia, arteriovenous malformations, and vascular aneurysms may be widely distributed throughout the cardiovascular system. It is usually recognized as a “triad” of telangiectasia, recurrent epistaxis, and a family history of the disorder.

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Osler-Rendu-Weber (ORW) Disease.

The different types of Osler-Rendu-Weber disease are classified according to either the gene map locus or, clinically, the presence or absence of pulmonary arteriovenous malformations.

• ORW I: Presence of pulmonary malformation with polycythemia and clubbing; mutation on the long arm of chromosome 9.
• ORW II: Absence of pulmonary malformation; gene map location is 12q11-q14.
• ORW III: Unlinked to either chromosome 9 or 12, in which the frequency of pulmonary arteriovenous fistulas is intermediate between the two first types. Patients seem to be more prone to have liver vascular malformations.

Incidence is estimated at 1:100,000 in the general population, but in some areas of the world the estimate is 1:40,000, and in Vermont, U.S., the estimate is 1:16,500. The difference in incidence observed probably is a result of the different subtypes.

All types of hereditary telangiectasia are autosomal dominant with some genetic heterogeneity but highly penetrant. The candidate genes are the genes for endoglin, CLO5A1 (type V collagen), and ZNF79, which all map to the long arm of chromosome 9.

The disease seems to result from the combination of defective perivascular connective tissue, insufficient smooth muscle contractile element, endothelial cell junction defects, and increased endothelial tissue plasminogen activator impairing thrombus formation in case of vascular damage.

Hereditary telangiectasia is a vascular dysplasia leading to telangiectasias and arteriovenous malformations of skin, mucosa, and viscera (especially tongue, lips, face, ears, and fingers), with a jaundiced appearance to the skin. Epistaxis and gastrointestinal bleeding are frequent complications of mucosal involvement. Visceral involvement includes that of the lung, liver, and brain. It may be difficult to differentiate from the CREST (calcinosis cutis, Raynaud phenomenon, esophageal motility disorder, sclerodactyly, and telangiectasia) syndrome. It is often associated with von Willebrand disease. The angiographic methods can demonstrate various types of visceral angiodysplasia, including arterial aneurysm, arteriovenous communication, including direct arteriovenous fistulas, conglomerate masses of angiectasia, phlebectasia, and angiomas. Pulmonary arteriovenous malformations may be life-threatening. Some are large enough to cause heart failure, polycythemia, and clubbing. Paradoxical emboli may cause abscess and infarction in the brain. Cirrhosis of the liver may occur with hepatic portocaval shunts of sufficient magnitude to cause repeated episodes of encephalopathy and esophageal varices. The arteriovenous malformations are also renal with episodic hematuria from mucosal telangiectasias and renal colic caused by clots. Migraine headaches are very common. The eyes are involved by conjunctival telangiectasia and retinal vascular malformations, but ...