JP-HHT phenotype in Danish patients with SMAD4 mutations

A M Jelsig, P M Tørring, A D Kjeldsen, N Qvist, A Bojesen, U B Jensen, M K Andersen, A M Gerdes, K Brusgaard, L B Ousager

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Patients with germline mutations in SMAD4 can present symptoms of both juvenile polyposis syndrome (JPS) and hereditary hemorrhagic telangiectasia (HHT): the JP-HHT syndrome. The complete phenotypic picture of this syndrome is only just emerging. We describe the clinical characteristics of 14 patients with SMAD4-mutations. The study was a retrospective, register-based study. SMAD4 mutations carriers were identified through the Danish HHT-registry, the genetic laboratories – and the genetic departments in Denmark. The medical files from relevant departments were reviewed and symptoms of HHT, JPS, aortopathy and family history were noted. We detected 14 patients with SMAD4 mutations. All patients had polyps removed and 11 of 14 fulfilled the diagnostic criteria for JPS. Eight patients were screened for HHT-symptoms and seven of these fulfilled the Curaçao criteria. One patient had aortic root dilation. Our findings support that SMAD4 mutations carriers have symptoms of both HHT and JPS and that the frequency of PAVM and gastric involvement with polyps is higher than in patients with HHT or JPS not caused by a SMAD4 mutation. Out of eight patients screened for aortopathy, one had aortic root dilatation, highlighting the need for additional screening for aortopathy.

Original languageEnglish
JournalClinical Genetics
Issue number1
Pages (from-to)55-62
Publication statusPublished - Jul 2016


  • Osler–Rendu disease
  • Smad4 protein
  • Smad4-related juvenile polyposis
  • epistaxis
  • hereditary hemorrhagic telangiectasia
  • juvenile polyposis syndrome
  • melena
  • Humans
  • Middle Aged
  • Aorta/metabolism
  • Male
  • Smad4 Protein/genetics
  • Adult
  • Female
  • Registries
  • Retrospective Studies
  • Gene Expression
  • Telangiectasia, Hereditary Hemorrhagic/complications
  • Neoplastic Syndromes, Hereditary/complications
  • Phenotype
  • Adolescent
  • Denmark
  • Heterozygote
  • Aged
  • Mutation
  • Intestinal Polyposis/complications


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