A novel germline BMPR1A variant (c.72_73delGA) in a Japanese family with hereditary mixed polyposis syndrome

Abstract

<jats:title>Abstract</jats:title> <jats:p>Hereditary mixed polyposis syndrome (HMPS) is a rare autosomal dominant disorder characterized by a mixture of typical and/or atypical juvenile polyps, adenomas and hyperplastic polyps, resulting in an increased risk of colorectal cancer. In HMPS, four different germline BMPR1A variants from five unrelated families have been reported. This study is the first to report HMPS within a Japanese family. The proband underwent repeated colonoscopic polypectomies over a 5-year period, since the age of 67. Histological examination of these resected polyps revealed adenomas, juvenile-like polyps and hyperplastic changes. Genetic testing was conducted to identify the causative genes for hereditary gastrointestinal cancer syndromes, including BMPR1A. We detected a germline variant, c.72_73delGA, in BMPR1A. The proband’s elder brother, younger sister and nephew have also undergone repeated colonoscopic polypectomies at other clinics. His sister and nephew underwent genetic testing, and the same BMPR1A variant was identified.</jats:p>

Re-recognition of BMPR1A-related polyposis: beyond juvenile polyposis and hereditary mixed polyposis syndrome

“…In our study, if we defined patient II1 as the proband, this family would also meet the diagnostic criteria for JPS because he provided a family history of JPS for other family members with fewer than five juvenile polyps. Similar situations have been reported for families in other studies [ 10 , 11 ]. Chow et al [ 10 ] noted the similarity of the family phenotype to that of HMPS in their JPS case.…”

“…The natural history of BMPR1A -associated polyposis (BAP) is not well documented. As seen in the reported studies [ 10 , 11 , 16 ] and our study, patients with BAP presented with a variety of polyps during long-term colonoscopic follow-up. With no clear pattern, the order in which various types of polyps occur is irregular.…”

“…Likewise, in pathological examinations, the diagnosis of a mixed polyp could be made based on some local features of the polyp, concluding a single pathological-type polyposis. To make a correct diagnosis, a complete polyp pathology or biopsy of all polyps is more appropriate; otherwise, BAP may be misdiagnosed as FAP [ 11 ].…”

A rare case of a juvenile polyp of patient with Peutz-Jeghers syndrome, complicated with intussusception of the small intestine

“…However, this diagnosis would require further investigation. [13] We report the unique case of a patient with PJS. Our patient underwent two surgical procedures in the course of the disease as we mentioned above.…”

“…HMPS is a rare autosomal dominant disease characterized by the appearance of different polyps, such as hyperplastic polyps, tubular adenomas, serrated adenomas, and hamartomatous polyps. [13] Although standard clinical diagnostic criteria for HMPS have yet to be firmly established, HMPS differs from JPS in that only a few typical juvenile polyps are documented. If typical juvenile polyps are present in HMPS, they are often associated with mixed components.…”