Hereditary hemorrhagic telangiectasia: Wikis


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Hereditary hemorrhagic telangiectasia
Classification and external resources
ICD-10 I78.0
ICD-9 448.0
OMIM 187300 600376 601101 610655
DiseasesDB 9303
eMedicine med/2764 ped/1668 derm/782
MeSH D013683

In medicine, hereditary hemorrhagic telangiectasia (also known as "Osler's disease," "Osler-Weber-Rendu disease"[1]:844, and Osler-Weber-Rendu syndrome,[2]) is an autosomal dominant genetic disorder that leads to vascular malformations.


Signs and symptoms

HHT is characterised by telangiectasia (small vascular malformations) on the skin and mucosal linings, epistaxis (nosebleeds), and arteriovenous malformations (AVMs) in various internal organs. Skin and mucosal telangiectasias are most remarkable on the tongue, hands/fingers, nose, lips, mouth/throat and conjunctiva.

The internal organs that can harbor AVMs often include the lungs, GI tract, brain, liver, and spine. In the brain and lungs, bleeding can seriously endanger life. Anemia may occur due to bleeding from digestive tract AVMs. High-output heart failure may develop in the presence of marked shunting arterial blood to the venous circulation, e.g. when AVMs are present in the liver. Liver failure and cirrhosis can develop as well on a vascular basis. Cerebral vascular accidents can occur due to small emboli bypassing the pulmonary vascular bed through a pulmonary AVM.


There are four diagnostic criteria, otherwise known as the Curacao criteria, named after the country where the meeting took place to formally define hereditary hemorrhagic telangiectasia.[3] If three or four are met, a patient has definite HHT, while two gives a possible diagnosis:

  1. Spontaneous recurrent epistaxis
  2. Multiple teleangiectasias on typical locations (see above)
  3. Proven visceral AVM (lung, liver, brain, spine)
  4. First-degree family member with HHT

When HHT is suspected, physical examination focuses on inspecting the skin for teleangiectasias, which are usually located on the digits, pinna, and bridge of the nose. Telangiectasias can also be seen with high frequency on the tongue and palate. In addition, auscultation of the liver for presence of bruits, and heart for high-output cardiac failure should be performed. A detailed neurological examination could reveal prior evidence of a stroke.

Pulmonary AVMs can be anticipated by measuring oxygen levels, sampling arterial blood gas (ABG), and performing a 2D echocardiogram with bubble study. An X-ray or CT of the chest can show lesions; in addition, low oxygen tension (<96% or a 2% decrease upon standing) or low blood oxygen levels on ABG are required for a diagnosis. CT and MRI of the brain can demonstrate cerebral AVMs. Abdominal ultrasound with doppler study or CT can show AVMs of the liver. Upper endoscopy, enteroscopy or capsule endoscopy can show gastrointestinal involvement. Rarely, telangiectasias can be demonstrated in the large intestine by colonoscopy.


Hereditary hemorrhagic telangiectasia has an autosomal dominant pattern of inheritance.

HHT is a genetic disorder by definition. It is inherited in an autosomal dominant manner.

Four forms have been described:

Name OMIM Gene/locus Description
HHT1 187300 endoglin (9q34.1). Endoglin is a receptor of TGFβ1 (transforming growth factor beta 1) and TGFβ3. It also interacts with zyxin and ZRP-1 with its intracellular domain, to control composition of focal adhesions and regulate organization of actin filaments. This form predisposes for pulmonary AVMs and early nosebleeds.
HHT2 600376 Alk-1 (12q11-q14) Alk-1 (activin receptor-like kinase 1) is a TGFβ1 receptor. Less pulmonary AVMs and later nosebleeds, but an increased risk of pulmonary hypertension (supposedly due to altered TGFβ signalling or other related pathways which may lead to vascular malformations).
HHT3 601101  ? at 5q31[4]?
Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome 175050 SMAD4 at 18q21.1
HHT4 610655  ? at 7p14. [5]? Identified in September 2006.

It is possible to test patients for the presence of mutations in endoglin, ALK-1 and SMAD4. When the mutation in an affected family member has been found it is possible to test other family members and identify those people not at risk for developing the disease.


The mechanism underlying the formation of vascular malformations is not completely understood, but signalling of transforming growth factor-β1 is most likely to be involved. Possibly, connective tissue is required to support and guide proliferating blood vessels during angiogenesis, and defects in TGF-β signalling adversely affect connective tissue and matrix production, leading to a weakness in vascular wall, so that vessels expand (teleangiectasia,fistulae) or even rupture.


There is no specific treatment for the condition, but complications can be addressed. Any patient undergoing dental work who has demonstrated pulmonary AVMs should have antibiotic prophylaxis. Anemia due to bleeding from digestive tract AVMs often necessitates repeated blood transfusions, intravenous iron therapy, and possible ablative therapy with cautery or argon plasma coagulation. Estrogen therapy is occasionally efficacious in chronic gastrointestinal blood loss. Interventional radiologists can ablate pulmonary AVMs with coil embolization. For severe nosebleeds, ENT physicians do not perform cauterization of the bleeding vessels anymore, while surgical procedures can be done, including nasal dermoplasty or even nostril closure. Rarely, a severe cardiac or liver failure from hepatic AVMs can necessitate a liver transplantation.


HHT occurs mainly in whites (1:5,000), more in certain areas of France, but much less in blacks (1 in 1 million). It is found in all continents throughout the world. It is also seen with increased frequency in Mormon families from Utah.

However, HHT is not limited to, nor found predominantly in people of a particular ethnic background, as are some genetic disorders.[6]

See also


  1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0.  
  2. ^ synd/1706 at Who Named It?
  3. ^ Shovlin CL, Guttmacher AE, Buscarini E, et al. (Mar 2000). "Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome)". Am J Med Genet 91 (1): 66–7. doi:10.1002/(SICI)1096-8628(20000306)91:1<66::AID-AJMG12>3.0.CO;2-P. PMID 10751092.  
  4. ^ Cole SG, Begbie ME, Wallace GM, Shovlin CL (2005). "A new locus for hereditary haemorrhagic telangiectasia (HHT3) maps to chromosome 5". J. Med. Genet. 42 (7): 577–82. doi:10.1136/jmg.2004.028712. PMID 15994879.  
  5. ^ Bayrak-Toydemir P, McDonald J, Akarsu N, et al. (2006). "A fourth locus for hereditary hemorrhagic telangiectasia maps to chromosome 7". Am. J. Med. Genet. A 140 (20): 2155–62. doi:10.1002/ajmg.a.31450. PMID 16969873.  
  6. ^ International HHT Foundation FAQ page -

External links



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