The gastrointestinal manifestation of constitutional mismatch repair deficiency syndrome: from a single adenoma to polyposis‐like phenotype and early onset cancer

Abstract

Data on the clinical presentation of constitutional mismatch repair deficiency syndrome (CMMRD) is accumulating. However, as the extraintestinal manifestations are often fatal and occur at early age, data on the systematic evaluation of the gastrointestinal tract is scarce. Here we describe 11 subjects with verified biallelic carriage and who underwent colonoscopy, upper endoscopy and small bowel evaluation. Five subjects were symptomatic and in six subjects the findings were screen detected. Two subjects had colorectal cancer and few adenomatous polyps (19, 20 years), three subjects had polyposis-like phenotype (13, 14, 16 years), four subjects had few adenomatous polyps (8, 12-14 years) and two subjects had no polyps (both at age 6). Of the three subjects in the polyposis-like group, two subjects had already developed high-grade dysplasia or cancer and one subject had atypical juvenile polyps suggesting juvenile polyposis. Three out of the five subjects that underwent repeated exams had significant findings during short interval. The gastrointestinal manifestations of CMMRD are highly dependent upon age of examination and highly variable. The polyps may also resemble juvenile polyposis. Intensive surveillance according to current guidelines is mandatory.

Teenage colorectal polyposis and cancer may be caused by constitutional mismatch repair deficiency (CMMRD)

“…Lack of CMMRD-related family history is also typical of previously described case reports [5]. The studied family case confirmed earlier published data that the current clinical criteria for Lynch syndrome are not sensitive enough to identify MSH6 mutation carriers [6].…”

Connections between constitutional mismatch repair deficiency syndrome and neurofibromatosis type 1

“…The spectrum of CMMRD‐associated malignancies can be separated in four main groups: (i) haematological malignancies with a predominance of T‐cell non‐Hodgkin lymphoma [for review see ]; (ii) high‐grade gliomas and other brain/central nervous system (CNS) tumours [for review see ]; (iii) colorectal and other carcinomas associated with Lynch syndrome [for review see ] and (iv) a miscellaneous group of malignancies seen less frequently in CMMRD including, amongst others, sarcomas and embryonic tumours [for review see ]. Most malignancies diagnosed in CMMRD patients fall in one of the first three groups, however, any malignancy in the paediatric age group may be a CMMRD associated one.…”

“…Among these, colorectal polyps, mainly adenomatous but occasionally also juvenile, are the most prevalent . There is evidence that gastrointestinal adenomas in CMMRD patients rapidly transform into carcinomas . In many patients, multiple synchronous adenomas ranging from a few up to 100 polyps are present mimicking (attenuated) familial adenomatous polyposis .…”

A 30-Year-Old Man with Three Primary Malignancies: A Case of Constitutional Mismatch Repair Deficiency

“…Another important feature is that the colonoscopy evaluation revealed multiple polyps, as previously reported in adults with CMMRD syndrome 6 , 7. Herkert et al described >10 adenomas in 18 of the 26 (70%) patients with colorectal cancer (CRC) and multiple CRC in 11 of 29 patients (38%) with CMMRD due to biallelic mutation of PMS2 8.…”