A case of gastric-localized juvenile polyposis syndrome with SMAD4 mosaic variant presenting as a slowly progressive phenotype.

Abstract

Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder caused by pathogenic variants in the mothers against decapentaplegic homolog 4 (SMAD4) and bone morphogenetic protein receptor type 1A (BMPR1A) genes. It is characterized by the development of multiple hamartomatous polyps in the gastrointestinal tract. We report a case of a 73-year-old Japanese male with sporadic, gastric-localized JPS harboring a SMAD4 mosaic variant who presented with slowly progressive endoscopic lesions. Endoscopy at the age of 55 revealed erythematous and edematous mucosa in the gastric fundus. During the following 18 years, the patient developed progressive gastric polyposis, leading to refractory anemia and hypoalbuminemia. Genetic testing identified a SMAD4 frameshift mosaic variant (c.1245_1248del (p.Asp415Glufs)) with an allele frequency of 23%. A total gastrectomy with D1 lymphadenectomy was performed, confirming the JPS diagnosis and the identification of a localized gastric adenocarcinoma without lymph node metastasis. This case highlights the unique natural history of JPS with a SMAD4 mosaic variant, which potentially contributes to a slowly progressive phenotype.