Multiple Brain Developmental Venous Anomalies as a Marker for Constitutional Mismatch Repair Deficiency Syndrome

Area of Science:

• Neuroscience
• Genetics
• Pediatric Oncology

Background:

• Constitutional mismatch repair deficiency syndrome (CMMRD) is a rare genetic disorder caused by mutations in DNA mismatch repair genes.
• CMMRD is characterized by childhood cancers, particularly brain tumors, necessitating surveillance protocols including brain MR imaging.
• Brain imaging in CMMRD patients has incidentally revealed a high prevalence of developmental venous anomalies (DVAs).

Purpose of the Study:

• To determine the prevalence of DVAs in patients diagnosed with CMMRD.
• To describe the phenotypic characteristics of DVAs in this patient cohort.
• To investigate the potential association between DVAs and CMMRD.

Main Methods:

• Retrospective analysis of brain MR imaging studies from 10 CMMRD patients across 3 families.
• Detailed assessment of DVA number, location, draining vessels, and associated vascular anomalies (e.g., cavernomas).
• Clinical correlation with patient symptoms and tumor status.

Main Results:

• All 10 CMMRD patients exhibited two or more DVAs.
• Two patients also had non-therapy-induced cavernomas.
• No DVAs caused symptomatic intracranial bleeding; brain tumors were not adjacent to DVAs.

Conclusions:

• Multiple DVAs appear to be a characteristic feature of CMMRD, a previously undescribed association.
• Confirming DVAs as a CMMRD marker could enhance diagnostic scoring systems.
• Early identification of DVAs may prompt genetic testing and surveillance, potentially improving patient outcomes.