Long QT Syndrome and Duodenal Ampullary Adenoma: A New Association

Abstract

Introduction: KCNQ 1 gene mutation has a well known association with long QT syndrome (LQTS). Recent research suggests that mutations in KCNQ1 gene may be implicated in the pathogenesis of intestinal neoplasia. We report the index case of duodenal ampullary adenoma in a patient with a history of long QT syndrome due to mutation of KCNQ1 gene. Case presentation: A 27 year old Hispanic man with a past medical history significant for congenital long QT syndrome due to KCNQ 1 (G168R) mutation, presented to the hospital with a two week history of deepening jaundice and pruritis. A contrast enhanced computed tomography (CT) scan showed obstruction at the level of ampulla causing dilatation of the biliary tree and pancreatic duct. Endoscopic retrograde cholangiopancreatography (ERCP) revealed a prominent ampulla (figure 1) with two small (2 mm) stones retrieved after biliary sphincterotomy was done. Ampullary biopsy was significant for adenomatous change with high grade dysplasia (figures 2,3). Subsequent endoscopic ultrasound (EUS) revealed an isoechoic, homogeneous mass measuring 10 mm in the ampulla without invasion of the muscularis propria. Endoscopic ampullectomy using a snare and electrocautery was performed. Biopsy specimens from the resected tissue revealed no evidence of neoplastic tissue. Screening colonoscopy was undertaken to assess for Familial adenomatous polyposis (FAP), however it only revealed three hyperplastic polyps. A follow up endoscopy with biopsy of the ampulla was done two months later, that did not show any neoplastic recurrence.Figure 1Figure 2Figure 3Discussion: Ampullary adenomas have been historically associated with FAP, in which they implicate a 124 fold increased risk of ampullary carcinoma. However, recent work in mice suggests that KCNQ1 gene mutations that have a well known association with LQTS, also increase the risk of intestinal tumors. Loss in KCNQ1 promoted tumor progression and enhanced tumor multiplicity. This might implicate KCNQ1 as a tumor suppressor gene. Surveillance endoscopy is recommended in ampullary adenomas after endoscopic papillectomy. This is usually performed 1 to 6 months after the index procedure with subsequent examinations every 3 to 12 months for at least 2 years. Conclusion: KCNQ1 has only recently been implicated as a tumor suppressor gene, however its role in LQTS has been well established. Since it is inherited in autosomal dominant fashion with high penetrance, the patients and their families need genetic counseling.