Information for Health Professionals

Hereditary mixed polyposis syndrome (HMPS)


Hereditary mixed polyposis syndrome (HMPS)

Hereditary mixed polyposis syndrome (HMPS OMIM 601228) is a mixed colorectal tumour syndrome which was originally linked to the CRAC1 locus on 15q13-14 (Thomas et al. 1996; Jaeger et al. 2003). It is a rare condition found in a few families of Ashkenazi descent, with an autosomal dominant inheritance, mixed juvenile, adenomatous and hyperplastic polyps, as well as colorectal cancer (Whitelaw et al. 1997). The best screening protocol for polyps in HMPS is not clear as the condition is rare.

Genome-wide association revealed common low-penetrance predisposition alleles at the CRAC1 locus which are linked to sporadic colorectal cancer risk (Jaeger et al. 2008). The gene which causes HMPS was subsequently identified as a 40kb duplication upstream of the gene GREM1 at the CRAC1 locus (Jaeger et al 2012) which causes disruption of the BMP / TGF-beta signalling pathway, a pathway also disrupted in Juvenile Polyposis Syndrome.

Simon Leedham showed that epithelial expression of GREM1 also occurs in traditional serrated adenomas, sporadic premalignant lesions with a hitherto unknown pathogenesis, and these lesions can be considered the sporadic equivalents of HMPS polyps (Davis et al. 2015).  They also elucidated the synergistic interaction of GREM1 with an activated Wnt signalling pathway.

Duplication upstream of GREM1

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About kjmonahan

Service lead for Family History of Bowel Cancer Clinic

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