Polygenic Infantile Juvenile Polyposis Syndrome Managed With Sirolimus and Endoscopic Polypectomy

Area of Science:

• Pediatric Gastroenterology
• Medical Genetics
• Pharmacology

Background:

• Juvenile polyposis syndrome (JPS) is a rare inherited disorder characterized by the development of numerous hamartomatous polyps in the gastrointestinal tract.
• Infantile JPS presents early in life with significant morbidity, including protein-losing enteropathy, anemia, and failure to thrive, often necessitating frequent surgical interventions.
• Current management strategies for severe JPS involve aggressive endoscopic and surgical polypectomy, which carry substantial risks and may not fully control disease progression.

Observation:

• A clinical case of infantile JPS is presented where sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, was administered.
• The patient experienced a significant reduction in disease burden following sirolimus initiation.
• Clinical improvements included resolution of protein-losing enteropathy, decreased intestinal blood loss, and improved weight gain.

Findings:

• Sirolimus administration was associated with a marked decrease in the number of polyps resected per unit time.
• The frequency of both upper and lower endoscopic evaluations required for polyp surveillance and management was reduced.
• While sirolimus mitigated many clinical sequelae of infantile JPS, it did not eliminate the need for ongoing aggressive polypectomy.

Implications:

• Sirolimus represents a promising pharmacologic agent for managing the systemic manifestations of infantile JPS, potentially reducing the need for extensive surgical resections.
• The combination of sirolimus and aggressive polypectomy may offer a more effective treatment paradigm for polygenic infantile JPS.
• Further research and clinical trials are warranted to establish the long-term efficacy and safety of sirolimus in pediatric patients with JPS.