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 visual loss is rare. Danazol, a weak synthetic androgen, may be a good treatment for immobilization of the major arteriovenous malformations.

An anesthesiology consultation is indicated before elective surgery. Check pulmonary and cardiac function to exclude high-output cardiac insufficiency and pulmonary arteriovenous malformations (clubbing). Check cell blood count (CBC) for anemia from bleeding or polycythemia from pulmonary shunt. Obtain a careful history of bleeding tendency. In case of doubt, test platelet function (often associated with the von Willebrand disease). Check renal and liver function. Perform a neurologic assessment to exclude previous paradoxical emboli and severe brain and medulla arteriovenous malformations leading to neurologic symptoms.

The condition may appear in the neonatal period. If the patient is treated with danazol, continue the medication until the morning of surgery. Pay special attention with use of locoregional anesthesia involving the neuraxial region because of the possibility of arteriovenous shunt, although no case in the literature describes a complication.

No specific implications with this condition other than those associated with the underlying medical problem (e.g., liver dysfunction, cardiac, and von Willebrand association). In case of von Willebrand association, consider administration of an octreopeptide.

CREST Syndrome: Scleroderma variant characterized by telangiectasia (morphologically indistinguishable from those of hereditary telangiectasia), sclerodactyly, Raynaud phenomenon, calcinosis, and esophageal motor dysfunction. Mucosal hemorrhage is not a main feature of CREST syndrome, whereas the presence of anticentromere antibodies is typical of CREST syndrome.

Louis-Bar Syndrome: Complex genetic neurodegenerative disorder that becomes apparent during infancy or early childhood. Characterized by progressive ataxia, telangiectasia, and impaired functioning of the immune system (i.e., cellular and humoral immunodeficiency), resulting in increased susceptibility to upper and lower respiratory tract infections (sinopulmonary infections). Other features include an increased risk of developing lymphomas, leukemia, and brain tumors. Progressive ataxia typically develops during infancy and usually is characterized by abnormal swaying of the head and trunk, dysarthria, drooling, and oculomotor apraxia and fixation nystagmus. Affected children may present with choreoathetosis movements. Telangiectasias may develop by midchildhood, often appearing on sun-exposed areas of the skin, such as the bridge of the nose, the ears, and certain regions of the extremities and conjunctiva. Inherited as an autosomal recessive trait.

von Willebrand-Jüergens Disease: Inherited blood clotting disorder characterized as deficiency of the von Willebrand factor protein and factor VIII protein (the factor VIII complex). Platelet adhesion is not functional, causing excessively slow clotting time and increased risk of excessive bleeding. von Willebrand disease has occurred in individuals who also have hereditary hemorrhagic telangiectasia.