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

• Published in: Clinical genetics Vol. 93; no. 1; pp. 134 - 137
• Main Authors: Suerink, M., Potjer, T.P., Versluijs, A.B., ten Broeke, S.W., Tops, C.M., Wimmer, K., Nielsen, M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.01.2018
• Subjects: bMMRD; cafe‐au‐lait macules; Cancer; Case reports; Children; CMMRD; Differential diagnosis; Genetic recombination; Genetic screening; hereditary cancer syndromes; HNPCC; Lynch syndrome; Mismatch repair; Mutation; Neurofibromatosis; PMS2; recessive genetic conditions; Recklinghausen's disease; Yeast; CMMRD; HNPCC; cafe-au-lait macules; hereditary cancer syndromes; PMS2; recessive genetic conditions; bMMRD; Lynch syndrome
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/cge.13053

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. CMMRD diagnosis in a child with café‐au‐lait macules and axillary freckling, but without malignancies: raising the question of when to test a healthy child.