Acute lymphoblastic leukemia and lymphoma in the context of constitutional mismatch repair deficiency syndrome

Eur J Med Genet. 2016 Mar;59(3):133-42. doi: 10.1016/j.ejmg.2015.12.014. Epub 2015 Dec 30.


Constitutional mismatch repair deficiency (CMMRD) syndrome is one of the rare diseases associated with a high risk of cancer. Causative mutations are found in DNA mismatch repair genes PMS2, MSH6, MSH2 or MLH1 that are well known in the context of Lynch syndrome. CMMRD follows an autosomal recessive inheritance trait and is characterized by childhood brain tumors and hematological malignancies as well as gastrointestinal cancer in the second and third decades of life. There is a high risk of multiple cancers, occurring synchronously and metachronously. In general, the prognosis is poor. About one third of CMMRD patients develop hematological malignancies as primary (sometimes the only) malignancy or as secondary neoplasm. T-cell non-Hodgkin lymphomas, mainly of mediastinal origin, are the most frequent hematological malignancies. Besides malignant diseases, non-neoplastic features are frequently observed, e.g. café-au-lait spots sometimes resembling neurofibromatosis type I, hypopigmented skin lesions, numerous adenomatous polyps, multiple pilomatricomas, or impaired immunoglobulin class switch recombination. Within the present review, we summarize previously published CMMRD patients with at least one hematological malignancy, provide an overview of steps necessary to substantiate the diagnosis of CMMRD, and refer to the recent most relevant literature.

Keywords: Acute lymphoblastic leukemia; Constitutional mismatch repair deficiency (CMMRD); Genetic predisposition; Pediatric cancer predisposition.

Publication types

  • Review

MeSH terms

  • Brain Neoplasms / epidemiology*
  • Brain Neoplasms / genetics*
  • Colorectal Neoplasms / epidemiology*
  • Colorectal Neoplasms / genetics*
  • Genetic Predisposition to Disease
  • Hematologic Neoplasms / epidemiology
  • Hematologic Neoplasms / etiology
  • Humans
  • Lymphoma / diagnosis
  • Lymphoma / epidemiology*
  • Lymphoma / etiology*
  • Lymphoma / therapy
  • Neoplasms, Second Primary*
  • Neoplastic Syndromes, Hereditary / epidemiology*
  • Neoplastic Syndromes, Hereditary / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / epidemiology*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / etiology*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy

Supplementary concepts

  • Turcot syndrome