Introduction: Juvenile Polyposis Syndrome (JPS) and Hereditary Hemorrhagic Telangiectasia (HHT) are rare disorders inherited in an autosomal dominant manner. The SMAD4 gene mutation causes a combined syndrome of JPS and HHT. We report a case of late-onset JPS-HHT overlap syndrome.
Case Description/Methods: A 72-year-old man presented with orthostasis and melena for three days. He had a lifetime history of recurrent epistaxis. Family history revealed two daughters with a history of gastrointestinal (GI) bleeding due to arteriovenous malformations (AVMs) and had required surgical gastrectomies for polyposis due to SMAD4 gene mutation. Physical exam revealed mild tachycardia. Rectal exam showed melena. There were no mucocutaneous telangiectasias. Hemoglobin (Hb) level was 4.4 g/dl and he had an elevated BUN to creatinine ratio. He was resuscitated and transfused. Upper endoscopy revealed multiple non-bleeding semi-sessile polyps in the stomach (Figure 1A). Colonoscopy was unremarkable and CT angiography showed no active bleeding. Capsule endoscopy a week later displayed numerous small bowel angiectasias that were subsequently treated with argon plasma coagulation (Figure 1B). Gastric biopsies showed foveolar hyperplasia and edema of the lamina propria consistent with inflammatory polyp of JPS (Figure 1C). He met the diagnostic criteria for the JPS-HHT overlap syndrome. He declined genetic testing for SMAD4 mutation. Follow-up included oral iron supplementation, and Hb level monitoring. Screening for GI malignancy as well as pulmonary and central nervous system AVMs was recommended.
Discussion: JPS often comes to clinical attention by age 20 years with most presenting with bleeding or anemia due to GI polyps. Individuals with JPS due to SMAD4 mutations often exhibit features of HHT [1] with GI bleeding related to HHT often presenting in the 4th decade of life. Our patient had delayed onset penetrance of the GI manifestations of both HHT and JPS with a first GI bleed at age 72 years. It is important for gastroenterologists to be aware of the varied age-related GI manifestations of the JPS-HHT overlap syndrome.
[1] Lin HC, Fiorino KN, Blick C, Anupindi SA. A rare presentation and diagnosis of juvenile polyposis syndrome and hereditary hemorrhagic telangiectasia overlap syndrome. Clin Imaging. 2015 Mar-Apr;39(2):321-4.
