What is HHT?

Hereditary Hemorrhagic Telangiectasia (HHT) is a genetic disorder of the blood vessels which affects about one in 8,000 people. It affects males and females from all racial and ethnic groups. The disorder is also referred to as Osler-Weber-Rendu (OWR) syndrome. In 1896 Dr. Rendu first described HHT as a hereditary disorder involving nosebleeds and characteristic red spots that was distinctly different from hemophilia. Dr. Rendu's work showed that individuals with HHT have abnormal blood vessels, and not a clotting problem in the blood itself. In the early 1900s, Drs. Weber and Osler reported on additional features of HHT.

About clinical diagnosis

The Scientific Advisory Board of the HHT Foundation International, Inc established these clinical criteria for diagnosis of HHT (the Curaçao criteria) in June 1999. More stringent than previous guidelines, the goals of the new criteria are to standardize research and to improve care of individuals with HHT.

The HHT diagnosis is classified as Definite if three criteria are present, Possible or Suspected if two criteria are present, and Unlikely if fewer than two criteria are present. The Curaçao criteria include the following:

1. Epistaxis - Spontaneous, recurrent nosebleeds
2. Telangiectases - Multiple at characteristic sites (lips, oral cavity, fingers, nose)
3. Visceral lesions - Such as Gastro-Intestinal telangiectasia (with or without bleeding), pulmonary AVM, hepatic AVM, cerebral AVM, spinal AVM
4. Family history - A first-degree relative with HHT

For further information about clinical diagnosis, see a specialist in HHT.

Genes linked to HHT

Three genes are currently associated with HHT. Mutations in the Endoglin (ENG) gene (HHT type 1) is more often associated with PAVMs. Mutations in the ALK1 gene (HHT type 2) are more often associated with a lower frequency of PAVMs and CAVMs than HHT type 1. Mutations in exons 8-11 of the SMAD4 gene have been associated with both HHT and juvenile polyposis (JP).

Most families with HHT have their own unique mutation. The position of the mutation does not influence the severity of disease, as it is loss of one functional copy of the gene and the consequential deficiency of a key signalling protein (i.e., reduced endoglin) that is believed to lead to the disorder. The spectrum of mutations spans all types of mutations and there are no known "hot spots" on the three genes: ENG, ALK1, and SMAD4.

Learn more about HHT

Click here for a thorough, recent and detailed description of HHT written by Alan E Guttmacher, MD, FACMG and Jamie McDonald, MS, CGC. This resource is posted on GeneReviews, developed at the University of Washington, Seattle and funded by the National Institutes of Health.

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