Familial Juvenile Polyposis Syndrome: A Case Report of a Cosegregation of SMAD4 Germline Pathogenic Variant c.403C>T and Review of the Literature.

Juvenile polyposis syndrome (JPS) is an inherited autosomal dominant disease that is distinguished by the emergence of numerous juvenile polyps within the gastrointestinal (GI) tract and has an increased risk of cancer. JPS is associated with germline mutations of the BMPR1A or SMAD4 genes. We aim to describe a case of familial occurrence of the SMAD4 germline pathogenic variant c.403C>T in a Brazilian family. We present a case of an 18-year-old female with rectal bleeding and chronic anemia who had a family history of colorectal issues-her mother had a total colectomy due to multiple polyps, and her maternal grandfather died from colorectal cancer (CRC). Despite a negative physical examination for attenuated familial adenomatous polyposis (AFAP) signs, a colonoscopy revealed around 30 proximal colon polyps of juvenile nature. These were systematically removed through multiple sessions, and an upper digestive endoscopy uncovered a few sessile inflammatory polyps. Notably, no polyps were found in the small intestine via double-balloon enteroscopy. After polyp removal, her bleeding episodes ceased, and her anemia resolved. She now maintains her health through biennial colonoscopies, upper digestive endoscopies, and endoscopic capsule procedures. Genetic testing identified a pathogenic mutation in exon 3 of the SMAD4 gene (c.403C>T), resulting in a truncated SMAD4 protein (p.Arg135 ∗). While previously documented in international databases, this represents the first report of a Brazilian family carrying this variant. Additionally, no mutations were found in the BMPR1A gene during genetic testing. In conclusion, molecular analysis confirmed the familial occurrence of the SMAD4 germline pathogenic variant c.403C>T within this Brazilian family.