The Gastrointestinal Manifestation of Constitutional Mismatch Repair Deficiency Syndrome

Objectives & Study:  Biallelic mismatch repair deficiency mutation is a new cancer syndrome characterized by childhood hematological malignancies, brain tumors, early age colonic adenomatous polyps, colonic and small bowel cancer. We aim to share our insights in a series of subjects that underwent comprehensive gastrointestinal work-up.
Methods: Included subjects with verified biallelic carriage that underwent complete gastrointestinal evaluation.
Results: Ten patients from 6 families were observed in this cohort.  These 10 patients were at a mean age of 13.3 years (range 6-20), 60% are male and their origin is Jewish and Arab equally. Consanguinity was noticed in 4 out of the six families. Two of our patients died at the age of 14 and 19 yr due to brain cancer.
Of the 10 cases, 5 (50%) had PMS2 mutations, 3 (30%) had MSH6 mutations, 1 (10%) had MSH2 mutations and 1(10%) had MSH2/MSH6 mutations. Eight patients had colonic involvement with adenomatous polyps in varying degree of dysplasia or cancer. Two of our youngest patients did not have colonic or gastric involvement at all. Regarding  xtraintestinal malignancies; 5 had high grade brain glioma and 1 had T-cell lymphoma. All of our patients have Neurofibromatosis like features – as Café au lait spots.
Conclusion: Biallelic mismatch repair deficiency syndrome is an unrecognized syndrome that combine gastrointestinal, hematological and brain tumors at the pediatric age. Their gastrointestinal manifestation includes multiple adenomatous polyps with varying degree of dysplasia including early cases of colonic cancer. Increasing awareness and knowledge of this syndrome can improve survival of these patients.