Gastrointestinal polyposis syndromes are primarily characterized by multiple polyps in the gastrointestinal tract, with their pathogenic mechanisms largely related to genetic factors and involving multiple signaling pathways. Adenomatous polyposis syndromes are mainly associated with APC gene variants, while some cases may arise from MUTYH gene variants. Peutz-Jeghers syndrome is primarily linked to STK11 gene variants. Juvenile polyposis syndrome is mainly associated with variants in the SMAD4 and BMPR1A genes. PTEN hamartoma tumor syndrome is predominantly caused by PTEN gene variants. Hereditary mixed polyposis syndrome is primarily related to variants of the GREM1 and BMPR1A genes. This article systematically summarizes the advances in genetic research on Gastrointestinal polyposis syndromes to enhance clinicians' understanding of these diseases and improve their diagnostic and therapeutic approaches.
Humans ; Adenomatous Polyposis Coli/genetics* ; Smad4 Protein/genetics* ; Peutz-Jeghers Syndrome/genetics* ; PTEN Phosphohydrolase/genetics* ; Bone Morphogenetic Protein Receptors, Type I/genetics* ; Intestinal Polyposis/congenital* ; Intercellular Signaling Peptides and Proteins/genetics* ; Adenomatous Polyposis Coli Protein/genetics* ; Protein Serine-Threonine Kinases/genetics* ; AMP-Activated Protein Kinase Kinases ; Neoplastic Syndromes, Hereditary

Bone Diseases ; complications ; Humans ; Intestinal Polyposis ; complications ; congenital ; Metaplasia ; complications ; Neoplastic Syndromes, Hereditary ; complications

Familial juvenile polyposis (FJP) is a rare autosomal dominant hereditary disorder that is characterized by the development of multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of cancer. Recently, germline mutations, including mutations in the SMAD4, BMPR1A, PTEN and, possibly, ENG genes, have been found in patients with juvenile polyps. We herein report a family with juvenile polyposis syndrome (JPS) with a novel germline mutation in the SMAD4 gene. A 21-year-old man presented with rectal bleeding and was found to have multiple polyps in his stomach, small bowel, and colon. His mother had a history of gastrectomy for multiple gastric polyps with anemia and a history of colectomy for colon cancer. A review of the histology of the polyps revealed juvenile polyps in both patients. Subsequently, mutation screening in DNA samples from the patients revealed a germline mutation in the SMAD4 gene. The pair had a novel mutation in exon 10 (stop codon at tyrosine 413). To our knowledge, this mutation has not been previously described. Careful family history collection and genetic screening in JPS patients are needed to identify FJP, and regular surveillance is recommended.
Exons ; Female ; Gastrointestinal Neoplasms/*genetics/pathology ; Germ-Line Mutation ; Humans ; Intestinal Polyposis/*congenital/genetics/pathology ; Male ; Middle Aged ; Neoplastic Syndromes, Hereditary/*genetics/pathology ; Smad4 Protein/*genetics ; Young Adult