GASTROINTESTINAL BLEEDING IN THE SETTING OF JUVENILE POLYPOSIS SYNDROME DUE TO SMAD4 MUTATION

Objectives: A 27-year-old female presented at thirteen weeks’ gestation with recurrent epigastric pain and anemia. She had a several year history of iron deficiency anemia requiring blood and iron transfusions. Upper endoscopy revealed a giant circumferential polyp and associated hyperplastic-appearing mucosal changes in the proximal stomach. Biopsies revealed hyperplasia with frequent lamina propria eosinophils without dysplasia or malignancy. She had no personal or family history of gastrointestinal neoplasia. Due to persistent anemia and the concern for occult malignancy in the mass, she was supported with intermittent transfusions until 34 weeks’ gestation, then labor was induced. After uneventful vaginal delivery of her son, total gastrectomy with pouch reconstruction and jejunostomy tube placement was performed at seven weeks post-partum. Final pathology of the operative specimen revealed multiple hyperplastic/hamartomatous polyps, negative for dysplasia or malignancy. She had an uncomplicated post-operative recovery, with resolution of her anemia. After genetic counseling, germline testing revealed monoallelic mutation of the SMAD4 gene and a diagnosis of Juvenile Polyposis Syndrome (JPS) was made. As JPS is an autosomal dominant disease and there are no other known cases of JPS in her family, this was felt to be a de novo mutation. Subsequent colonoscopy demonstrated multiple benign polyps in the cecum.

JPS is caused by germline mutations in the SMAD4 or BMPR1A genes and is characterized by predisposition to hamartomatous polyps in the gastrointestinal tract, including the stomach, small bowel, colon, and rectum. “Juvenile” refers to the pathologic appearance of the polyps rather than the age of polyp onset, however most individuals begin to develop polyps prior to age 20 years. While most JPS-associated polyps are benign, malignant transformation can occur. Up to two-thirds of mutations in JPS are thought to arise de novo, and therefore one should have low threshold to send patients for genetic counseling and screening when multiple polyps are found in a young patient, even in the absence of family history. The risk of colorectal cancer development is 20% by age 35 and as high as 65-70% by age 60. For those with gastric polyps, lifetime gastric cancer risk is about 20%. Patients with JPS should be monitored for gastrointestinal bleeding, anemia, abdominal pain, or changes in bowel habits or stool caliber or color. In the absence of symptoms, colonoscopy and upper endoscopy should begin at 15 years and repeat annually in the setting of polyps or once every 2-3 years in the absence of polyps.

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