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

Abstract

Background Bone morphogenetic protein receptor type 1A (BMPR1A) is responsible for two individual Mendelian diseases: juvenile polyposis syndrome and hereditary mixed polyposis syndrome 2, which have overlapping phenotypes. This study aimed to elucidate whether these two syndromes are just two subtypes of a single syndrome rather than two isolated syndromes. Methods We sequenced the BMPR1A gene in 186 patients with polyposis and colorectal cancer, and evaluated the clinicopathological features and phenotypes of the probands and their available relatives with BMPR1A mutations. Results BMPR1A germline mutations were found in six probands and their three available relatives. The numbers of frameshift, nonsense, splice-site, and missense mutations were one, one, two, and two, respectively; two of the six mutations were novel. Typical juvenile polyps were found in only three patients. Two patients had colorectal cancer rather than any polyps. Conclusions Diseases in BMPR1A germline mutation carriers vary from mixed polyposis to sole colorectal cancer, and typical juvenile polyps do not always occur in these carriers. The variety of phenotypes reflected the features of BMPR1A-mutation carriers, which should be recognized as a spectrum of one syndrome. Genetic testing may be a good approach to identifying BMPR1A-related syndromes.

The Progress of Colorectal Polyposis Syndrome in Chinese Population

“…Typical juvenile polyps were only found in 3 patients, and adenomatous polyps, mixed polyps, and CRC were found in other patients. Gao et al reported a patient with BMPR1A c.949_952 delCTCT, p.Leu317Metfs à 4 (the same as the one reported by Zhao et al 73 ) with adenomatous polyps as phenotype, which was clinically misdiagnosed as FAP. 74 Pathogenic variant of SMAD4 leads to juvenile polyposis (JPS) and hereditary hemorrhagic telangiectasia, and 40% of patients may also have thoracic aortic disease.…”

“…56 Zhao et al recently published the results of a trial of BMPR1A-associated polyps in Chinese population. 73 A total of 166 patients with colorectal polyps and 20 patients diagnosed with CRC before age 50 were enrolled. Patients with positive genetic tests are evaluated according to the corresponding clinical diagnostic criteria for JPS or HMPS.…”

Juvenile polyposis syndrome (review)

“…У носителей патогенного варианта гена BMPR1A редко встречается поражение верхних отделов ЖКТ, а проявления заболевания в толстой кишке варьируют от наличия смешанного полипоза (в кишке определяются как ювенильные, так и аденоматозные полипы) до выявления колоректального рака на фоне отсутствия полипов в толстой кишке [38]. Некоторые авторы даже выделяют отдельный вид полипозного синдрома -наследственный смешанный полипозный синдром (hereditary mixed polyposis syndrome -HMPS), отмечая при этом его обусловленность патогенными вариантами гена BMPR1A [39,40].…”