Keinosuke Hizuka1, Shin-Ichiro Hagiwara2, Takatoshi Maeyama1, Hitoshi Honma1, Masanobu Kawai1, Kiwamu Akagi3, Michiko Yasuhara4, Naohiro Tomita4,5, Yuri Etani1. 1. Department of Gastroenterology, Nutrition and Endocrinology, Osaka Women's and Children's Hospital, 840 Murodo-cho, Izumi, Osaka, 594-1101, Japan. 2. Department of Gastroenterology, Nutrition and Endocrinology, Osaka Women's and Children's Hospital, 840 Murodo-cho, Izumi, Osaka, 594-1101, Japan. hagi114@wch.opho.jp. 3. Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, 780, Komuro, Ina-machi, Kitaadachi-gun, Saitama, 780362-0806, Japan. 4. Division of Lower GI Surgery, Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan. 5. Cancer Treatment Center, Toyonaka Municipal Hospital, 4-14-1, Shibahara-cho, Toyonaka, Osaka, 560-8565, Japan.
Abstract
BACKGROUND: 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. CASE PRESENTATION: 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. CONCLUSIONS: 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.
BACKGROUND: 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. CASE PRESENTATION: 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. CONCLUSIONS: 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.
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