hereditary hemorrhagic telangiectasia

Definition: Hereditary hemorrhagic telangiectasia (HHT) is a genetic angiodysplasia affecting multiple organs, characterized by cutaneous, mucosal, and visceral vascular anomalies.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia leading to telangiectases and arteriovenous malformations of skin, mucosa, and viscera. Epistaxis and gastrointestinal bleeding are frequent complications of mucosal involvement. Visceral involvement includes that of the lung, liver, and brain.

The most frequent form of hereditary hemorrhagic telangiectasia maps to the long arm of chromosome 9 (HHT1) and is due to mutations in the ENG gene coding for endoglin.

Types

 hereditary haemorrhagic telangiectasia (HHT)

• HHT1 at 9q34.1 (MIM.187300) : endoglin (ENG) (MIM.131195)
• HHT2 at 12q11-q14 (MIM.600376) : ACVRL1 gene (MIM.601284)

 hereditary haemorrhagic telangiectasia with digestive juvenile polyposis (JHPT)

Synopsis

 vascular lesions (26%) (12843319)

• telangiectases
  • mucosal telangiectases
  • conjunctival telangiectases
  • nail bed telangiectases
  • finger pad telangiectases

• digestive angiodysplastic lesions (esophagus, stomach, small intestine colon) (14%) (12843319)

• arteriovenous malformations (AVM)
  • pulmonary arteriovenous malformation (PAVM) (4%) (12843319)
  • cerebral arteriovenous malformation (CAVM) (3%) (12843319)
  • coronary arteriovenous malformation (9671858)
  • celiac arterioveinous malformation
  • mesenteric arterioveinous malformation
  • hepatic arterioveinous malformation (and cirrhosis)
  • cerebral arterioveinous malformation
  • spinal arterioveinous malformation

• pulmonary capillary hemangiomatosis (14991548)
• arterial aneurysms
• venous varicosities

 hemorrhages

• epistaxis
• subarachnoid hemorrhage
• intracerebral hemorrhage
• digestive hemorrhages

Variants

 HHT and digestive juvenile polyposis (JHT syndrome) (MIM.175050) (11795766, 9892274, 8165825)

• MADH4 (SMAD4) mutations (MIM.600993) at 18q21.1

Etiology

 Locus HHT1: mutation in the gene encoding endoglin (ENG) (MIM.131195) at 9q34.1
 Locus HHT2: mutations in the activin receptor-like kinase-1 gene (ACVRLK1) (MIM.601284) at 12q11-q14
 Locus HHT3 (localization unknown; gene unknown)
 Locus JP-HHT (juvenile polyposis and HHT): MADH4 mutations (MIM.600993) at 18q21.1