Neuroimaging Findings in Children with Constitutional Mismatch Repair Deficiency Syndrome

Area of Science:

• Pediatric Oncology
• Neuroimaging
• Genetics

Background:

• Constitutional mismatch repair deficiency (CMMRD) is a rare hereditary cancer predisposition syndrome affecting children.
• CMMRD is characterized by an increased risk of brain tumors, colorectal, and hematologic malignancies.
• Understanding the neuroimaging features of CMMRD is crucial for early diagnosis and management.

Purpose of the Study:

• To describe the characteristic neuroimaging findings in pediatric patients diagnosed with CMMRD.
• To identify specific patterns on brain MRI that may suggest CMMRD.
• To correlate imaging findings with clinical presentation and tumor types.

Main Methods:

• Retrospective analysis of 14 children with genetically confirmed CMMRD.
• Patients were referred from two tertiary pediatric oncology centers.
• Review of brain MRI findings, including tumor characteristics and non-neoplastic abnormalities.

Main Results:

• Brain malignancy was the most common presentation, affecting 13 of 14 patients.
• High-grade gliomas (glioblastoma, anaplastic astrocytoma) were the most frequent brain tumors.
• Nonspecific T2 hyperintensities in the white matter were observed in 71% of patients, with some progressing to tumors; developmental venous anomalies were present in 85%.

Conclusions:

• Brain MRI in CMMRD patients shows characteristic multifocal high-grade gliomas and nonspecific white matter changes, potentially indicating early neoplastic transformation.
• A high incidence of developmental venous anomalies is noted in CMMRD patients.
• Recognizing this specific constellation of imaging findings (phenotypic gestalt) is vital for raising suspicion of CMMRD in diagnostic and surveillance imaging, potentially improving patient outcomes.