Familial Cancer

, Volume 18, Issue 1, pp 105–108 | Cite as

Delineating a new feature of constitutional mismatch repair deficiency (CMMRD) syndrome: breast cancer

  • Lisa BushEmail author
  • Melyssa Aronson
  • Uri Tabori
  • Brittany B. Campbell
  • Raymond B. Bedgood
  • Kory Jasperson
Short Communication


Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare autosomal recessive hereditary cancer condition, characterized by an exceptionally high risk of cancer, a propensity for childhood malignancies, and cutaneous features reminiscent of neurofibromatosis type 1 (NF1). We report on two sisters originally suspected of having CMMRD syndrome due to their history of colonic polyps and NF1 associated skin findings, both were subsequently found to have biallelic MSH6 mutations. After years of CMMRD syndrome follow-up, the proband was diagnosed with breast cancer at age 29, while her sister was diagnosed with a glioblastoma at age 27. Immunohistochemistry analysis on the breast tumor tissue revealed weak MSH6 protein staining. Exome sequencing revealed a hypermutated breast tumor and an ultra-hypermutated brain tumor. Multi-gene panel testing was also performed and revealed no additional mutations which might explain the proband’s early onset breast cancer. This is the first documented case of breast cancer in an individual with CMMRD syndrome. We summarize the evidence supporting the possible association between breast cancer and biallelic MMR mutations. Healthcare providers should be aware of this possible association and follow-up appropriately for suspicious breast findings. In addition, this case highlights the need for frequent central nervous system screenings due to rapid progression of brain tumors.


Constitutional mismatch repair deficiency syndrome MSH6 CMMRD Lynch syndrome Hereditary breast cancer Hereditary brain tumor 



We would like to thank the family for their dedication to helping improve the lives of others affected by CMMRD syndrome through fundraising, advocacy, research and raising awareness.


The mutation burden analysis was funded through the SU2C Catalyst Research Grant and the Canadian Institute of Health Research Joint Israel-Canada Health Program.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interests.

Informed consent

Obtained. This study was approved by the Mount Sinai Hospital Institutional Review Board. The family is enrolled in the Familial Gastrointestinal Cancer Registry (FGICR) and the International BMMRD Consortium.


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Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Hereditary Cancer ProgramNorthside Hospital Cancer InstituteAtlantaUSA
  2. 2.Zane Cohen Centre for Digestive Diseases, Mount Sinai HospitalUniversity of TorontoTorontoCanada
  3. 3.Division of Haematology/Oncology, The Hospital for Sick ChildrenUniversity of TorontoTorontoCanada
  4. 4.Program in Genetics and Genome Biology, The Hospital for Sick ChildrenUniversity of TorontoTorontoCanada
  5. 5.Gastroenterology Associates of Central GeorgiaMaconUSA
  6. 6.Department of Medical AffairsAmbry GeneticsAliso ViejoUSA

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