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Disease expression in juvenile polyposis syndrome: a retrospective survey on a cohort of 221 European patients and comparison with a literature-derived cohort of 473 SMAD4/BMPR1A pathogenic variant carriers

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  • Robert Blatter
  • Benjamin Tschupp
  • Stefan Aretz
  • Inge Bernstein
  • Chrystelle Colas
  • D Gareth Evans
  • Maurizio Genuardi
  • Frederik J Hes
  • Robert Hüneburg
  • Heikki Järvinen
  • Fiona Lalloo
  • Gabriela Moeslein
  • Laura Renkonen-Sinisalo
  • Nicoletta Resta
  • Isabel Spier
  • Dora Varvara
  • Hans Vasen
  • Andrew R Latchford
  • Karl Heinimann
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PURPOSE: Juvenile polyposis syndrome (JPS) is a rare, autosomal-dominantly inherited cancer predisposition caused in approximately 50% of cases by pathogenic germline variants in SMAD4 and BMPR1A. We aimed to gather detailed clinical and molecular genetic information on JPS disease expression to provide a basis for management guidelines and establish open access variant databases.

METHODS: We performed a retrospective, questionnaire-based European multicenter survey on and established a cohort of SMAD4/BMPR1A pathogenic variant carriers from the medical literature.

RESULTS: We analyzed questionnaire-based data on 221 JPS patients (126 kindreds) from ten European centers and retrieved literature-based information on 473 patients. Compared with BMPR1A carriers, SMAD4 carriers displayed anemia twice as often (58% vs. 26%), and exclusively showed overlap symptoms with hemorrhagic telangiectasia (32%) and an increased prevalence (39% vs. 13%) of gastric juvenile polyps. Cancer, reported in 15% of JPS patients (median age 41 years), mainly occurred in the colorectum (overall: 62%, SMAD4: 58%, BMPR1A: 88%) and the stomach (overall: 21%; SMAD4: 27%, BMPR1A: 0%).

CONCLUSION: This comprehensive retrospective study on genotype-phenotype correlations in 694 JPS patients corroborates previous observations on JPS in general and SMAD4 carriers in particular, facilitates recommendations for clinical management, and provides the basis for open access variant SMAD4 and BMPR1A databases.

Original languageEnglish
JournalGenetics in medicine : official journal of the American College of Medical Genetics
Issue number9
Pages (from-to)1524-1532
Number of pages9
Publication statusPublished - Sep 2020

    Research areas

  • colorectal cancer, genotype–phenotype correlation, hereditary hemorrhagic telangiectasia, juvenile polyposis syndrome, polyposis

ID: 59856548