Ongoing issues with the management of children with Constitutional Mismatch Repair Deficiency syndrome

Eur J Med Genet. 2019 Aug;62(8):103706. doi: 10.1016/j.ejmg.2019.103706. Epub 2019 Jun 21.


Constitutional Mismatch Repair Deficiency (CMMRD) is a rare cancer predisposition syndrome, presenting in childhood, in which affected patients develop various malignancies such as hematological, gastrointestinal and central nervous system tumors. Although guidelines are being increasingly developed for surveillance and early detection of cancers in affected families, there are no clear recommendations regarding choice of therapy and very scarce information about tolerance to chemotherapy and radiation in these patients. We report the pedigree of a consanguineous family with four affected children. Although clinical and molecular tests confirm CMMRD, genetic testing revealed heterogeneous mutations. The index case developed severe toxicity from therapy for glioblastoma and T-cell leukemia and died from an infection while in complete remission. His sister developed a malignant brain tumor while undergoing surveillance for a low grade brain lesion and is still undergoing follow-up. This family illustrates the difficulties and opportunities with challenging diagnosis, surveillance and choice of therapy for children with CMMRD and the need for increased awareness and more information about this rare but important syndrome.

Keywords: BrainTumor; CMMRD; Constitutional mismatch repair deficiency syndrome; GI malignancies; Genetic predisposition to cancer; Glioblastoma multiforme; Lynch syndrome; Surveillance; T-cell leukemia.

Publication types

  • Letter

MeSH terms

  • Brain Neoplasms / complications
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy*
  • Colorectal Neoplasms / complications
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / therapy*
  • Consanguinity
  • Female
  • Genetic Testing*
  • Humans
  • Male
  • Mutation
  • Neoplasms / complications
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Neoplastic Syndromes, Hereditary / complications
  • Neoplastic Syndromes, Hereditary / genetics
  • Neoplastic Syndromes, Hereditary / pathology
  • Neoplastic Syndromes, Hereditary / therapy*
  • Pedigree
  • Precancerous Conditions / complications
  • Precancerous Conditions / genetics
  • Precancerous Conditions / pathology
  • Precancerous Conditions / therapy*

Supplementary concepts

  • Turcot syndrome