A case of an inversion (18)(q11.2q21.1) associated with juvenile polyposis.

Juvenile polyposis syndrome (JPS) is an autosomal dominant cancer predisposing syndrome. It is genetically heterogenous, and is distinct from Cowden and Bayanyan-Zonana syndromes. Germline mutations in BMPR1A and SMAD4/DPC4 have been identified in patients with JPS; both are components of the TGF beta signalling pathway. Juvenile polyps from carriers of SMAD4 mutations may have a greater malignancy potential than those who do not. A 25 year old male presented with rectal bleeding. Initially twelve polyps were found, three of which were removed and were reported to be adenomatous. Subsequent investigations over several years revealed multiple juvenile polyps and review of the original polypectomy specimens led to their re-classification as juvenile polyps. He also developed numerous subcutaneous angiolipomas and severe asthma. His karyotype was found to be 46XY inv(18)(q11.2q21.1). FISH analysis using PAC probe 224-j-22 which encompasses the 11 exon SMAD4 gene, located at 18q21.1, was disrupted by this inversion. We believe this is the first repod of a visible cytogenetic rearrangement causing JPS. Further work is underway to determine whether inactivation of SMAD4 has played a role in development of his angiolipomas. [ABSTRACT FROM AUTHOR]