Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu Syndrome)

Epidemiology

Demographics

  • Incidence: 1 in 5000 to 1 in 8000 in France, Denmark, and Japan
    • Higher prevalence in isolated communities

Etiology

  • Autosomal Dominant
    • Mutations in endoglin-1 (HHT1) and ALK-1 (HHT2) genes (play role in TGFß signaling): mutations result in decreased levels of these proteins on vascular endothelium
    • HHT1 mutations may produce earlier onset of vascular complications than other mutations
    • HHT2 mutations also are at risk for pulmonary HTN (similar to those with BMPR2 mutations)
    • Mutations in Smad4 (HHT3) (play role in TGFß signaling): results in juvenile polyposis-HHT overlap syndrome

Physiology

  • Disorder of vascular development

Clinical Manifestations

Dermatologic Manifestations

  • Mucocutaneous Telangiectasias (see Telangiectasias, Telangiectasias)
    • Epidemiology
      • Usually Diagnosed in Adulthood (Usually Absent or Subtle Earlier in Life)
    • Physiology
      • Mucocutaneous Telangiectasias Develop Progressively with Aging
    • Clinical: usually cosmetic (bleeding is uncommon and rarely clinically significant)
      • Buccal Mucosa: common site
      • Lips: common site
      • Tongue: common site
      • Fingertips: common site

Gastrointestinal/Hepatic Manifestations

  • Gastrointestinal Telangiectasias
    • Epidemiology
      • Approximately 33% of Cases Experience Recurrent Gastrointestinal Hemorrhage
      • Most Cases of Gastrointestinal Hemorrhage Occur in Patients >40 y/o
    • Physiology
      • Gastrointestinal Telangiectasias Develop Progressively with Aging
    • Clinical
      • Telangiectasias May Occur Anywhere in the Gastrointestinal Tract
        • Gastric Telangiectasias: common site
        • Duodenal Telangiectasias: common site
        • Colonic Telangiectasias: less common site
      • Gastrointestinal Hemorrhage (see Gastrointestinal Hemorrhage, Gastrointestinal Hemorrhage)
  • Hepatic Telangiectasias
    • Epidemiology: hepatic involvement occurs in approximately 66% of cases (although it is usually asymptomatic)
    • Clinical
  • Pancreatic Arteriovenous Malformation (AVM)
    • Diagnosis: may be diagnosed by CT

Neurologic Manifestations

Otolaryngologic Manifestations

  • Nasal Muscosal Telangiectasias
    • Epidemiology: common early in the course (with onset during childhood)
    • Clinical: epistaxis (see Epistaxis, Epistaxis)

Pulmonary Manifestations


Treatment

  • Family Screening: no child of an affected parent can be excluded from having HHT without genetic testing

References

Clinical

  • Hereditary haemorrhagic telangiectasia and pulmonary arteriovenous malformations: issues in clinical management and review of pathogenic mechanisms. Thorax. 1999;54(8):714 [MEDLINE]
  • Low serum iron levels are associated with elevated plasma levels of coagulation factor VIII and pulmonary emboli/deep venous thromboses in replicate cohorts of patients with hereditary haemorrhagic telangiectasia. Thorax. 2012 Apr;67(4):328-33. Epub 2011 Dec 14 [MEDLINE]
  • Ischaemic strokes in patients with pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia: associations with iron deficiency and platelets. PLoS One. 2014;9(2):e88812. Epub 2014 Feb 19 [MEDLINE]
  • Pulmonary hypertension in hereditary haemorrhagic telangiectasia. World J Cardiol. 2015 May;7(5):230-7 [MEDLINE]

Treatment

  • Antiplatelet and anticoagulant agents in hereditary hemorrhagic telangiectasia. N Engl J Med. 2013 Feb;368(9):876-8 [MEDLINE]