Neuroimaging Findings in Children with Constitutional Mismatch Repair Deficiency Syndrome

AJNR Am J Neuroradiol. 2020 May;41(5):904-910. doi: 10.3174/ajnr.A6512. Epub 2020 Apr 30.


Background and purpose: Constitutional mismatch repair deficiency is a hereditary childhood cancer predisposition syndrome characterized by brain tumors and colorectal and hematologic malignancies. Our objective was to describe the neuroimaging findings in patients with constitutional mismatch repair deficiency.

Materials and methods: This retrospective study included 14 children with genetically confirmed constitutional mismatch repair deficiency who were referred to 2 tertiary pediatric oncology centers.

Results: Fourteen patients from 11 different families had diagnosed constitutional mismatch repair deficiency. The mean age at presentation was 9.3 years (range, 5-14 years). The most common clinical presentation was brain malignancy, diagnosed in 13 of the 14 patients. The most common brain tumors were glioblastoma (n = 7 patients), anaplastic astrocytoma (n = 3 patients), and diffuse astrocytoma (n = 3 patients). Nonspecific subcortical white matter T2 hyperintensities were noted in 10 patients (71%). Subcortical hyperintensities transformed into overt brain tumors on follow-up imaging in 3 patients. Additional non-neoplastic brain MR imaging findings included developmental venous anomalies in 12 patients (85%) and nontherapy-induced cavernous hemangiomas in 3 patients (21%).

Conclusions: On brain MR imaging, these patients have both highly characteristic intra-axial tumors (typically multifocal high-grade gliomas) and nonspecific findings, some of which might represent early stages of neoplastic transformation. The incidence of developmental venous anomalies is high in these patients for unclear reasons. Awareness of these imaging findings, especially in combination, is important to raise the suspicion of constitutional mismatch repair deficiency in routine diagnostic imaging evaluation or surveillance imaging studies of asymptomatic carriers because early identification of the phenotypic "gestalt" might improve outcomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Brain Neoplasms / complications
  • Brain Neoplasms / diagnostic imaging*
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Child
  • Child, Preschool
  • Colorectal Neoplasms / complications*
  • Female
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Mutation
  • Neoplastic Syndromes, Hereditary / complications*
  • Neuroimaging
  • Retrospective Studies

Supplementary concepts

  • Turcot syndrome