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Genotype-phenotype relationship in hereditary haemorrhagic telangiectasia
  1. T G W Letteboer1,
  2. J J Mager2,
  3. R J Snijder2,
  4. B P C Koeleman1,
  5. D Lindhout1,
  6. J K Ploos van Amstel1,
  7. C J J Westermann2
  1. 1DBG-Department of Medical Genetics, University Medical Center Utrecht, The Netherlands
  2. 2St Antonius Hospital, Nieuwegein, The Netherlands
  1. Correspondence to:
 Dr T G W Letteboer
 DBG-Department of Medical Genetics, University Medical Center Utrecht, PO Box 85090, 3508 AB Utrecht, The Netherlands; t.g.w.letteboer{at}


Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterised by vascular malformations in multiple organ systems, resulting in mucocutaneous telangiectases and arteriovenous malformations predominantly in the lungs (pulmonary arteriovenous malformation; PAVM), brain (cerebral arteriovenous malformation; CAVM), and liver (hepatic arteriovenous malformation; HAVM). Mutations in the ENG and ALK-1 genes lead to HHT1 and HHT2 respectively. In this study, a genotype-phenotype analysis was performed. A uniform and well classified large group of HHT patients and their family members were screened for HHT manifestations. Groups of patients with a clinically confirmed diagnosis and/or genetically established diagnosis (HHT1 or HHT2) were compared. The frequency of PAVM, CAVM, HAVM, and gastrointestinal telangiectases were determined to establish the genotype-phenotype relationship. The analysis revealed differences between HHT1 and HHT2 and within HHT1 and HHT2 between men and women. PAVMs and CAVMs occur more often in HHT1, whereas HAVMs are more frequent in HHT2. Furthermore, there is a higher prevalence of PAVM in women compared with men in HHT1. In HHT1 and HHT2, there is a higher frequency of HAVM in women. HHT1 has a distinct, more severe phenotype than HHT2. There is a difference in the presence of symptoms between men and women. With these data, genetic counselling can be given more accurately when the family mutation is known.

  • CAVM, cerebral arteriovenous malformation
  • CT, computed tomography
  • GI, gastrointestinal
  • HAVM, hepatic arteriovenous malformation
  • HHT, hereditary haemorrhagic telangiectasia
  • MRI, magnetic resonance imaging
  • PAVM, pulmonary arteriovenous malformation
  • hereditary haemorrhagic telangiectasia
  • Rendu-Osler-Weber disease
  • ENG
  • ALK-1
  • phenotype-genotype relation
  • arteriovenous malformation

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  • Published Online First 9 September 2005

  • Competing interests: there are no competing interests.