Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Schwetz, V.
Manifestations of Juvenile Polyposis Syndrome in SMAD4 Mutation Carriers of a Kindred
[ Diplomarbeit ] Medical University of Graz; 2010. pp. 87
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- Autor*innen der Med Uni Graz:
- Theiler-Schwetz Verena
- Betreuer*innen:
- Hoegenauer Christoph
- Uhrig Sabine
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- Abstract:
- Background/Aims: Juvenile polyposis syndrome (JPS) is an autosomal dominantly inherited syndrome leading to the development of multiple hamartomatous polyps of the entire gastrointestinal tract. Causative are germline mutations of three genes - SMAD4, BMPR1A and ENG. They encode for proteins involved in the TGF-ß pathway, a molecular mechanism regulating biological processes such as cell proliferation and immune modulation. On the basis of juvenile polyps adenomas with different grades of intraepithelial neoplasia and subsequently adenocarcinoma can develop. Family members of affected JPS patients should therefore undergo genetic testing. Regular upper and lower gastrointestinal endoscopy are recommended for mutation carriers. Based on a SMAD4 mutation positive family, the hypothesis was postulated that juvenile polyps occur not only in the stomach, small intestine and colon but also in the biliary tract and the gallbladder - a manifestation not yet described in the literature. Methods: In the course of this prospective case study 8 affected SMAD4 mutation positive family members were screened for manifestations of JPS by means of endoscopy, sonography, and further imaging. Consequently, adequate therapy was carried out. Results: Of these 8 affected family members, two were symptomatic at the time of diagnosis, six were asymptomatic - independent of the severity of the manifestation. The time span between the occurrence of the first symptoms and the correct diagnosis was six months for the index patient and 3 years for her relative. Each gene carrier presented with juvenile polyps in the colon, 5/8 with gastric manifestation in addition. In one patient early gastric cancer was detected, another showed a villous adenoma with high-grade intraepithelial neoplasia in the colon - both patients were asymptomatic. 2/8 patients presented with polyps in the gallbladder - in one case histological evaluation revealed cholesterol polyps and 1/8 with a bile duct hamartoma confirmed in biopsy. Significance: (1) All SMAD4 mutation carriers showed manifestations of JPS, the severity of which differing substantially. (2) 6/8 patients had an asymptomatic course of disease and were diagnosed only by genetic screening. (3) The two symptomatic patients had their correct diagnosis confirmed six months resp. three years after the occurrence of the first symptoms. (4) It remains controversial whether JPS occurs in the gallbladder and biliary tract - a manifestation not yet described in in the literature, but if verified crucial for surveillance of SMAD4 mutation carriers.