Constitutional Mismatch Repair Deficiency Syndromes, a Neurofibromatosis 1 Mimicker That Hinders Timely Management.

BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) is a rare, autosomal recessive disease caused by a biallelic germline mutation in one of the DNA mismatch repair genes (MLH1, MSH2, MSH6, and PMS2). In addition to the colorectal, brain, and hematological malignancies, many additional premalignant and nonmalignant features that can point toward the diagnosis of CMMRD have been reported.

METHODS: The report from the CMMRD consortium revealed that all children with CMMRD have café-au-lait macules (CALMs) but the number of CALMs does not reach >5 in all CMMRD patients, which is one of the diagnostic criteria of neurofibromatosis 1 (NF1).

RESULTS: About half of the patients with CMMRD develop brain tumors and up to 40% develop metachronous second malignancies. All 5 patients in our cohort developed brain tumors and showed a predilection to the frontal lobe. In our cohort, multiple Mongolian spots, coloboma, obesity, congenital heart disease, dysmorphism, and clubfoot were also encountered.

CONCLUSION: In all our patients, NF1 and other tumorigenic predisposing syndromes were initially suspected. Increasing awareness of this condition and its shared reminiscent NF1 features, particularly CALMs among child neurologists, oncologists, geneticists, and dermatologists can help uncover the tip of the iceberg of CMMRD that carries an important consequence on management.