Clinical symptoms according to genotype amongst patients with hereditary haemorrhagic telangiectasia

J Intern Med. 2005 Oct;258(4):349-55. doi: 10.1111/j.1365-2796.2005.01555.x.


Background: Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease, characterized by a wide variety of clinical manifestations, including epistaxis, gastrointestinal (GI) bleeding, pulmonary arteriovenous malformations (PAVMs) and neurological symptoms. HHT is a genetically heterogeneous disorder involving at least two loci; HHT 1 mapping to chromosome 9 q 34.1 (ENG) and HHT 2 mapping to chromosome 12 q 31 (ALK-1).

Objective: To evaluate and describe the diversity of clinical manifestations in a Danish population of HHT patients with known HHT 1 or HHT 2 subtype.

Design: Prospective clinical examination with genetic evaluation and follow-up.

Setting: Investigation centre was Odense University Hospital. All HHT patients in the County of Fyn were included.

Methods: HHT family members were invited to a clinical examination including registration of HHT manifestations, screening for PAVM and neurological evaluation. Blood tests were performed for analysis of disease-causing mutation, and clinical manifestations in the HHT subtypes were compared. The survival of the patients was studied in the follow-up period.

Results: Included in the study were 73 HHT patients representing 18 families. In 14 of the families we identified a disease-causing mutation. Thirty-nine patients (from 10 families) had HHT1 and 16 HHT patients from four families had HHT2.

Conclusion: Amongst patients with HHT1 genotype the prevalence of PAVM was higher than amongst HHT patients with HHT2 genotype. HHT1 patients had experienced more severe GI bleeding than HHT2 patients. There was no significant difference in severity of epistaxis or age at debut. Finally the mortality over a 90-month observation period was not significantly increased.

Publication types

  • Comparative Study

MeSH terms

  • Activin Receptors, Type I / genetics*
  • Activin Receptors, Type II
  • Adolescent
  • Adult
  • Aged
  • Antigens, CD
  • Arteriovenous Malformations / complications
  • Arteriovenous Malformations / genetics
  • Arteriovenous Malformations / mortality
  • Chi-Square Distribution
  • DNA Mutational Analysis
  • Endoglin
  • Epistaxis / complications
  • Epistaxis / genetics
  • Epistaxis / mortality
  • Female
  • Gastrointestinal Hemorrhage / complications
  • Gastrointestinal Hemorrhage / genetics
  • Gastrointestinal Hemorrhage / mortality
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Point Mutation*
  • Prevalence
  • Pulmonary Artery
  • Pulmonary Veins
  • Receptors, Cell Surface
  • Survival Rate
  • Telangiectasia, Hereditary Hemorrhagic / complications
  • Telangiectasia, Hereditary Hemorrhagic / genetics*
  • Telangiectasia, Hereditary Hemorrhagic / mortality
  • Vascular Cell Adhesion Molecule-1 / genetics*


  • Antigens, CD
  • ENG protein, human
  • Endoglin
  • Receptors, Cell Surface
  • Vascular Cell Adhesion Molecule-1
  • ACVRL1 protein, human
  • Activin Receptors, Type I
  • Activin Receptors, Type II