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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.
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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.
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- 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.
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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.
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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.
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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.
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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 ...