Constitutional mismatch repair deficiency in a healthy child: On the spot diagnosis?

Clinical Genetics
M SuerinkM Nielsen

Abstract

Constitutional mismatch repair deficiency (CMMRD) is a rare, recessively inherited childhood cancer predisposition syndrome caused by biallelic germline mutations in one of the mismatch repair genes. The CMMRD phenotype overlaps with that of neurofibromatosis type 1 (NF1), since many patients have multiple café-au-lait macules (CALM) and other NF1 signs, but no germline NF1 mutations. We report of a case of a healthy 6-year-old girl who fulfilled the diagnostic criteria of NF1 with >6 CALM and freckling. Since molecular genetic testing was unable to confirm the diagnosis of NF1 or Legius syndrome and the patient was a child of consanguineous parents, we suspected CMMRD and found a homozygous PMS2 mutation that impairs MMR function. Current guidelines advise testing for CMMRD only in cancer patients. However, this case illustrates that including CMMRD in the differential diagnosis in suspected sporadic NF1 without causative NF1 or SPRED1 mutations may facilitate identification of CMMRD prior to cancer development. We discuss the advantages and potential risks of this CMMRD testing scenario.

References

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Apr 17, 2014·Journal of Medical Genetics·Katharina WimmerUNKNOWN EU-Consortium Care for CMMRD (C4CMMRD)
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Citations

Dec 30, 2017·Clinical Genetics·J Blount, A Prakash
Sep 11, 2019·Journal of Medical Genetics·Helen ToledanoYael Goldberg
May 12, 2019·Der Hautarzt; Zeitschrift für Dermatologie, Venerologie, und verwandte Gebiete·H HammJ Olk
Aug 11, 2020·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Juan A Perez-ValenciaKatharina Wimmer
Dec 16, 2018·Bulletin du cancer·Bruno BuecherChrystelle Colas

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