Genetic condition awaiting consideration - Hereditary Haemorrhagic Telangiectasia or Rendu-Osler-Weber Syndrome
Hereditary haemorrhagic telangiectasia (HHT) is characterized by the presence of multiple arteriovenous malformations (AVMs) that lack intervening capillaries and result in direct connections between arteries and veins.
HHT is a developmental disorder with a variable age of onset; infants being occasionally severely affected, but in most cases features appear in childhood (age-dependent features) and usually are not diagnosed until adolescence or later.
Small arteriovenous malformations close to the surface of the skin and mucous membranes often rupture and bleed after slight trauma.
The most common clinical manifestation is spontaneous and recurrent nose bleeds (epistaxis) beginning on average at age 12 years.
Approximately 25% of individuals with HHT have GI bleeding, which most commonly begins after the age of 50 years.
Large arteriovenous malformations often cause symptoms when they occur in the brain, liver, or lungs; complications like bleeding or shunting that may be sudden and catastrophic.
The diagnosis of HHT is based on the presence of epistaxis, cutaneous or mucosal telangiectases, visceral AVMs, family history and presence of a pathogenic mutation.
HHT is caused by mutations in a number of genes involved in the TGF-ß/BMP signalling cascade: ENG, the gene encoding the cell surface co-receptor endoglin; ACVRL1 (ALK1), also a gene encoding a cell surface receptor; and SMAD4, a gene encoding an intracellular signalling molecule. Molecular genetic testing of ENG, ALK1 and SMAD4 detects mutations in approximately 80%-87% of individuals who meet unequivocal clinical diagnostic criteria for HHT.
HHT is an autosomal dominant syndrome with an estimated prevalence between 1:2,500 and 1:40,000 in all races and all parts of the world and considerable intra-familial variability. Most individuals have an affected parent.
Each child of a proband and the sibs of most probands have a 50% risk of inheriting the mutation.
Prenatal testing is possible for pregnancies at increased risk if the disease causing mutation in the family is known.
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Page last updated: 16 July 2012