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

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Keinosuke Hizuka ◽  
Shin-ichiro Hagiwara ◽  
Takatoshi Maeyama ◽  
Hitoshi Honma ◽  
Masanobu Kawai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mismatch Repair ◽  
De Novo ◽  
Pathological Examination ◽  
Compound Heterozygous ◽  
Mismatch Repair Deficiency ◽  
Repair Deficiency ◽  
Compound Heterozygous Variants ◽  
De Novo Variant ◽  
Constitutional Mismatch Repair Deficiency

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.

Constitutional mismatch repair deficiency and Lynch syndrome among consecutive Arab Bedouins with colorectal cancer in Israel

2017 ◽  
Vol 17 (1) ◽  
pp. 79-86 ◽  
Author(s):  
Naim Abu Freha ◽  
Yaara Leibovici Weissman ◽  
Alexander Fich ◽  
Inbal Barnes Kedar ◽  
Marisa Halpern ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Mismatch Repair ◽  
Mismatch Repair Deficiency ◽  
Repair Deficiency ◽  
Constitutional Mismatch Repair Deficiency

scholarly journals Intensive surveillance endoscopy for multiple gastrointestinal tumors in a patient with constitutional mismatch repair deficiency: case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Takayuki Ando ◽  
Takahiko Nakajima ◽  
Rei Fukuda ◽  
Keiko Nomura ◽  
Yo Niida ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Mismatch Repair ◽  
Mismatch Repair Deficiency ◽  
Aggressive Approach ◽  
Repair Deficiency ◽  
Partial Colectomy ◽  
Surveillance Endoscopy ◽  
Constitutional Mismatch Repair Deficiency ◽  
Intensive Surveillance

Abstract Background Constitutional mismatch repair deficiency (CMMRD) is an extremely rare autosomal recessive hereditary disease characterized by the absence of mismatch repair gene activity from birth, which results in brain tumors, colonic polyposis, gastrointestinal cancers, and lymphomas later in life. An aggressive approach, including colectomy or proctocolectomy, is recommended for the treatment of colorectal cancer. Additionally, partial colectomy with subsequent endoscopic surveillance may be an alternative strategy due to poor patient’s condition, although there is no evidence of surveillance endoscopy after partial colectomy for CMMRD. Case presentation A 13-year-old male patient with a history of T-lymphoblastic lymphoma underwent total gastrointestinal endoscopy, which revealed rectal cancer, colorectal polyposis, and duodenal adenoma. Differential diagnosis included constitutional mismatch repair deficiency according to its scoring system and microsatellite instability, and subsequent germline mutation testing for mismatch repair genes confirmed the diagnosis of constitutional mismatch repair deficiency based on a homozygous mutation in mutS homolog 6 (MSH6). The patient and his family refused colectomy due to the high risk of malignancies other than colorectal cancer, which could require radical surgery. Therefore, the patient underwent low anterior resection of the rectosigmoid colon for rectal cancer and intensive surveillance endoscopy for the remaining colon polyposis. During the 3-year period after initial surgery, 130 polyps were removed and the number of polyps gradually decreased during 6-months interval surveillance endoscopies, although only one polyp was diagnosed as invasive adenocarcinoma (pT1). Conclusions Our experience of short surveillance endoscopy illustrates that this strategy might be one of options according to patient’s condition.

scholarly journals RARE-55. CHALLENGES AND SPECIFIC STRATEGIES FOR CONSTITUTIONAL MISMATCH REPAIR DEFICIENCY SYNDROME IN LOW RESOURCE SETTINGS. ON BEHALF OF THE INTERNATIONAL RRD CONSORTIUM IN LOW RESOURCE SETTINGS PANEL

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii454-iii454
Author(s):  
Rejin Kebudi ◽  
Nisreen Amayiri N ◽  
Malak Abedalthagafi ◽  
Asim Noor Rana ◽  
Slman Kirmani ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Checkpoint Inhibitors ◽  
Immune Therapy ◽  
Malignant Gliomas ◽  
Mismatch Repair Deficiency ◽  
Term Survival ◽  
Low Resource Settings ◽  
Low Resource ◽  
Repair Deficiency ◽  
Constitutional Mismatch Repair Deficiency

Abstract Germline biallelic mutations in one of the mismatch repair genes (MSH2/MSH6/MLH1/PMS2 results in constitutional mismatch repair deficiency (CMMRD), a condition associated with multiple tumors arising from multiple organs during childhood, and these individuals rarely reach adulthood. The paucity of information with respect to these conditions leads to mismanagement and may be a factor in the high mortality of patients with CMMRD. Two international consortia, the European CARE4CMMRD, and the international replication repair deficiency (RRD) consortium, are addressing the many challenges associated with this condition. To address specific issues surrounding the management of CMMRD in low and middle income countries (LMIC), a multidisciplinary taskforce of 11 specialists from nine countries was formed. Preliminary conclusions are: 1) Immunohistochemistry for CMMRD should be considered for all patients with suggestive clinical features. In countries where CMMRD is common, malignant gliomas, colon cancers and T cell lymphomas should be stained routinely as the prevalence of CMMRD in these tumors can exceed 40%. 2) Temozolomide should not be used in the management of malignant glioma. By contrast, preclinical studies have suggested increased sensitivity to nitrosoureas. For the management of CMMRD related lymphoma and leukemia, mercaptopurines should not be avoided or discontinued as a part of the standard of care before more data are collected. 3) Management with checkpoint inhibitors should be limited to centers with intensive care units and expertise in complex supportive care to manage side effects of immune therapy. 4) Surveillance protocols have demonstrated long term survival benefits and should be implemented in LMIC.

scholarly journals The Challenge of Diagnosing Constitutional Mismatch Repair Deficiency Syndrome in Brain Malignancies from Young Individuals

2021 ◽  
Vol 22 (9) ◽  
pp. 4629
Author(s):  
Cristina Carrato ◽  
Carolina Sanz ◽  
Ana María Muñoz-Mármol ◽  
Ignacio Blanco ◽  
Marta Pineda ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Mismatch Repair ◽  
Rare Event ◽  
Deficiency Syndrome ◽  
Mismatch Repair Deficiency ◽  
Malignant Brain Tumors ◽  
Repair Deficiency ◽  
Clinical Awareness ◽  
High Degree ◽  
Constitutional Mismatch Repair Deficiency

Biallelic germline mismatch repair (MMR) gene (MLH1, MSH2, MSH6, and PMS2) mutations are an extremely rare event that causes constitutional mismatch repair deficiency (CMMRD) syndrome. CMMRD is underdiagnosed and often debuts with pediatric malignant brain tumors. A high degree of clinical awareness of the CMMRD phenotype is needed to identify new cases. Immunohistochemical (IHC) assessment of MMR protein expression and analysis of microsatellite instability (MSI) are the first tools with which to initiate the study of this syndrome in solid malignancies. MMR IHC shows a hallmark pattern with absence of staining in both neoplastic and non-neoplastic cells for the biallelic mutated gene. However, MSI often fails in brain malignancies. The aim of this report is to draw attention to the peculiar IHC profile that characterizes CMMRD syndrome and to review the difficulties in reaching an accurate diagnosis by describing the case of two siblings with biallelic MSH6 germline mutations and brain tumors. Given the difficulties involved in early diagnosis of CMMRD we propose the use of the IHC of MMR proteins in all malignant brain tumors diagnosed in individuals younger than 25 years-old to facilitate the diagnosis of CMMRD and to select those neoplasms that will benefit from immunotherapy treatment.

Gender difference for mismatch repair deficiency in human colorectal cancer

2001 ◽  
Vol 121 (4) ◽  
pp. 1026-1027 ◽  
Author(s):  
Alex Duval ◽  
Barry Iacopetta ◽  
Lin Thorstensen ◽  
Gunn Iren Meling ◽  
Ragnhild A. Lothe ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gender Difference ◽  
Mismatch Repair ◽  
Mismatch Repair Deficiency ◽  
Human Colorectal Cancer ◽  
Repair Deficiency
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