Constitutional mismatch repair deficiency in childhood colorectal cancer harboring a de novo variant in the MSH6 gene: a case report

• Published in: BMC gastroenterology 2021-02, Vol.21 (1), p.60-60, Article 60
• Main Authors: Hizuka, Keinosuke, Hagiwara, Shin-Ichiro, Maeyama, Takatoshi, Honma, Hitoshi, Kawai, Masanobu, Akagi, Kiwamu, Yasuhara, Michiko, Tomita, Naohiro, Etani, Yuri
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Brain Neoplasms - genetics; Brain tumors; Café-au-lait macules; Cancer in children; Case Report; Case reports; Case studies; Child; Childhood; Children; Chromosomal instability syndromes; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Constitutional mismatch repair deficiency; Diarrhea; DNA Mismatch Repair - genetics; DNA-Binding Proteins - genetics; Endoscopy; Female; Gastroenterology; Genes; Genetic aspects; Genetic screening; Humans; Magnetic resonance imaging; Mismatch repair; Mismatch repair gene; MSH6 gene; MSH6 protein; Mutation; Neoplastic Syndromes, Hereditary - genetics; Neurofibromatosis; Neurofibromatosis type1; Neuroimaging; Ovaries; Patients; Pediatric research; Phenotypes; Polyps; Protein expression; Recklinghausen's disease; Surgery; Tumors
• ISSN: 1471-230X; 1471-230X
• DOI: 10.1186/s12876-021-01646-3

Constitutional mismatch repair deficiency (CMMRD) is caused by biallelic pathogenic variants in one of the mismatch repair genes, and results in early onset colorectal cancer, leukemia, brain tumors and other childhood malignancies. Here we report a case of CMMRD with compound heterozygous variants in the MSH6 gene, including a de novo variant in multiple colorectal cancers. An 11-year-old girl, who presented with multiple spots resembling café-au-lait macules since birth, developed abdominal pain, diarrhea and bloody stool over two months. Colonoscopy revealed multiple colonic polyps, including a large epithelial tumor, and pathological examination revealed tubular adenocarcinoma. Brain magnetic resonance imaging (MRI) showed an unidentified bright object (UBO), commonly seen in neurofibromatosis type 1 (NF1). Genetic testing revealed compound heterozygous variants, c. [2969T > A (p.Leu990*)] and [3064G > T (p.Glu1022*)] in the MSH6 gene; c.2969T > A (p.Leu990*) was identified as a de novo variant. We present the first report of a CMMRD patient with a de novo variant in MSH6, who developed colorectal cancer in childhood. CMMRD symptoms often resemble NF1, as observed here. Physicians should become familiar with CMMRD clinical phenotypes for the screening and early detection of cancer.