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.
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:
- Epistaxis – Spontaneous, recurrent nosebleeds
- Telangiectases – Multiple at characteristic sites (lips, oral cavity, fingers, nose)
- Visceral lesions – Such as Gastro-Intestinal telangiectasia (with or without bleeding), pulmonary AVM, hepatic AVM, cerebral AVM, spinal AVM
- 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) are more often associated with PAVMs. Mutations in the ACVRL1 gene (HHT type 2) lead to a lower frequency of PAVMs than HHT type 1, and show a higher incidence of liver involvement. Clinical features of the disease do not reliably indicate whether the gene mutated is ENG or ACVRL1. Mutations in the (MADH4) SMAD4 gene (most often in exons 8 through 11) have been associated with JP- HHT.
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, ACVRL1, and SMAD4.