Large- and medium-sized arterial aneurysms in two patients with SMAD4-related juvenile polyposis syndrome

Am J Med Genet A. 2024 Oct;194(10):e63605. doi: 10.1002/ajmg.a.63605. Epub 2024 May 16.

Abstract

Germline SMAD4 pathogenic variants (PVs) cause juvenile polyposis syndrome (JPS), which is known for an increased risk of gastrointestinal juvenile polyps and gastrointestinal cancer. Many patients with SMAD4 PV also show signs of hereditary hemorrhagic telangiectasia (HHT) and some patients have aneurysms and dissections of the thoracic aorta. Here we describe two patients with a germline SMAD4 PV and a remarkable clinical presentation including multiple medium-sized arterial aneurysms. More data are needed to confirm whether the more extensive vascular phenotype and the other described features in our patients are indeed part of a broader JPS spectrum.

Keywords: Kawasaki; SMAD4; aneurysm; connective tissue disorder; juvenile polyposis syndrome.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Aneurysm* / complications
  • Aneurysm* / genetics
  • Aneurysm* / pathology
  • Female
  • Genetic Predisposition to Disease
  • Germ-Line Mutation / genetics
  • Humans
  • Intestinal Polyposis* / complications
  • Intestinal Polyposis* / congenital
  • Intestinal Polyposis* / diagnosis
  • Intestinal Polyposis* / genetics
  • Intestinal Polyposis* / pathology
  • Male
  • Middle Aged
  • Neoplastic Syndromes, Hereditary* / complications
  • Neoplastic Syndromes, Hereditary* / genetics
  • Neoplastic Syndromes, Hereditary* / pathology
  • Phenotype
  • Smad4 Protein* / genetics
  • Telangiectasia, Hereditary Hemorrhagic / complications
  • Telangiectasia, Hereditary Hemorrhagic / genetics
  • Telangiectasia, Hereditary Hemorrhagic / pathology

Substances

  • Smad4 Protein
  • SMAD4 protein, human

Supplementary concepts

  • Juvenile polyposis syndrome