P1792 - AXIN2 Mutation: A Toothless Cause of Hereditary Colorectal Cancer

Ana Martinez-Tapia, MD¹, Amit Sah, MD², Hayden Aaron, MD^3
1Larkin Community Hospital, Miami, FL; ²University of Miami, Atlantis, FL; ³West Palm Veterans Affairs Medical Center, West Palm Beach, FL

Introduction: AXIN2 is a protein in the WNT signaling pathway responsible for embyogenesis, including development of teeth and hair. Germline mutation of AXIN2 is a rare genetic cause of adenomatous polyposis (AP) and colorectal cancer development (CRC) accounting for less than 2.5% in general population. Typical features of carriers include tooth agenesis (oligodontia), sparse hairs and eyebrows, AP and CRC. We present a case of AXIN2 carrier without the typical phenotype who underwent genetic testing upon request due to AP on screening colonoscopy.

Case Description/Methods: A 62 yr-old female with no significant past medical history was found to have 4 sessile polyposis on surveillance colonoscopy. She started screening colonoscopy at age 50 but since 2017, she is having more frequent colonoscopies given findings of tubulo-villous adenomas. Her mother died from CRC at age 79. She has a ‘healthy’ sister that has not been screened for CRC. She has multiple chronic gastrointestinal complaints but no change in stool caliber or unintentional weight loss. These symptoms along with family history of CRC prompted her to request for an elective genetic testing. She had Invitae genetic panel which was positive for deleterious AXIN2 mutation.

Discussion: There are only a few cases in literature regarding the susceptibility of AXIN2 mutation and CRC development. Due to an autosomal dominant inheritance pattern, genetic testing and counselling should be considered for family members carrying this mutation. More than 90% of the carriers showed AP on colonoscopy, 40% had CRC or other digestive cancer and 60% had oligodontia. There is variable penetrance, thus not all patients have typical phenotypes as described in the literature. Our patient had advanced polyposis and no other features of AXIN2 mutation. She was diagnosed with this high-risk hereditary mutation due to elective genetic testing request. Currently guidelines recommend to begin CRC screening at age 25 due to possibility of high polyp burden which sometimes requires colectomy. With broadening of genome database and new knowledge regarding hereditary CRC mutations, genetic panel might be considered as a screening test in some high-risk individual with polyposis, regardless of typical features. Additionally, early research shows AXIN2 as a useful biomarker in detecting AP in CRC patients. However, current guidelines for colonoscopy in AXIN2 carriers are still evolving, and further research and close follow-up regarding updated recommendations are essential.



Disclosures:


Ana Martinez-Tapia, MD¹, Amit Sah, MD², Hayden Aaron, MD³. P1792 - AXIN2 Mutation: A Toothless Cause of Hereditary Colorectal Cancer, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.