Constitutional mismatch repair-deficiency syndrome presenting as colonic adenomatous polyposis: clues from the skin
Article first published online: 6 OCT 2010
© 2010 John Wiley & Sons A/S
Volume 80, Issue 4, pages 394–397, October 2011
How to Cite
Jasperson, K., Samowitz, W. and Burt, R. (2011), Constitutional mismatch repair-deficiency syndrome presenting as colonic adenomatous polyposis: clues from the skin. Clinical Genetics, 80: 394–397. doi: 10.1111/j.1399-0004.2010.01543.x
- Issue published online: 8 SEP 2011
- Article first published online: 6 OCT 2010
- Accepted manuscript online: 16 SEP 2010 12:12AM EST
- Received 16 July 2010, revised and accepted for publication 13 September 2010
- colonic adenomatous polyposis;
- constitutional mismatch repair-deficiency syndrome;
- Lynch syndrome;
Jasperson KW, Samowitz WS, Burt RW. Constitutional mismatch repair-deficiency syndrome presenting as colonic adenomatous polyposis: clues from the skin.
Constitutional mismatch repair-deficiency (CMMR-D) syndrome is an autosomal recessive condition characterized by hematologic malignancies, brain tumors, Lynch syndrome-associated cancers and skin manifestations reminiscent of neurofibromatosis type 1 (NF1). In contrast to Lynch syndrome, CMMR-D syndrome is exceptionally rare, onset typically occurs in infancy or early childhood and, as described in this report, may also present with colonic polyposis suggestive of attenuated familial adenomatous polyposis (AFAP) or MUTYH associated polyposis (MAP). Here we describe two sisters with CMMR-D syndrome due to germline bi-allelic MSH6 mutations. Both sisters are without cancer, are older than typical for this condition, have NF1 associated features and a colonic phenotype suspicious for an attenuated polyposis syndrome. This report highlights the role of skin examinations in leading to an underlying genetic diagnosis in individuals with colonic adenomatous polyposis, but without mutations associated with AFAP or MAP.