There are limited data on the effectiveness of cancer screening in biallelic MMR-gene pathogenic variant carriers. Published recommendations represent expert opinion and are mostly extrapolated from cancer screening studies in other groups at increased risk of specific cancers.
Colorectal adenomas are common (estimated lifetime penetrance >90%) with more than 50% of reported CMMRD cases having adenoma detected before age 10 years.r Multiple colorectal adenomas have been diagnosed in a child aged 6 years.r There is in vitro evidence that CMMRD-related adenoma show faster progression from benign to malignant than equivalent lesions in heterozygotes (i.e. Lynch syndrome). Consider increasing colonoscopy to 6 monthly if adenoma are detected.
One of the most commonly reported cancers is colorectal carcinoma (CRC), with approximately 50% of reported CRC diagnosed under age 16 years.rr Colonoscopy is of proven benefit in a number of inherited colorectal polyposis syndromes and it is reasonable to assume at least some benefit in CMMRD. There is no published data on the long term benefits of preventative colectomy in CMMRD.
Small bowel cancer
A recent report from the International BMMRD Consortium detailed the outcome of video capsule endoscopy (VCE) for small bowel surveillance in 17 patients with CMMRD (total of 38 procedures).r Three patients had small bowel neoplasia detected by VCE (2 with adenoma with high grade dysplasia at 16 and 13 years, 1 with jejunal adenocarcinoma at 15 years). However 4 patients with negative VCE were subsequently diagnosed with duodenal neoplasia (false negatives).
Some experts recommend 6 monthly FBE with differential from age 12 months. There is no evidence that this leads to earlier detection of haematological malignancy, reduced mortality or improved survival.
Brain tumours have similar penetrance to CRC, but with a younger median age at diagnosis (9 years). There are multiple reports of brain tumours in children under age 5 years.rrrr