A case of Constitutional Mismatch Repair Deficiency (CMMRD)

@#Constitutionalmismatch repair deficiency(CMMRD) is a hereditary predisposition of malignancy evident in childhood leukemias, lymphomas, and malignant tumors of the brain, GI tract. It is a very rare condition that affects 1 per 1 million patients. Patients with CMMRD syndrome may also manifest with Neurofibromatosis Type 1 (NF1) phenotypic features, and benign masses, particularly in the gastrointestinal tract. This is a case of a 12-year old male who presented with phenotypic features of NF1, developed Acute Lymphoblastic Leukemia at 7 years old and went into remission. He subsequently developed synchronous Glioblastoma and Poorly differentiated Adenocarcinoma of the rectum.This report aims to raise awareness regarding the possibility of a CMMRD syndrome in pediatric patients who present with phenotypic features of NF1, and in those patients who present with two or more malignancies in their lifetime.

Pediatric High Grade Gliomas in the Context of Cancer Predisposition Syndromes

Germline mutations in cancer causing genes result in high risk of developing cancer throughout life. These cancer predisposition syndromes (CPS) are especially prevalent in childhood brain tumors and impact both the patient's and other family members' survival. Knowledge of specific CPS may alter the management of the cancer, offer novel targeted therapies which may improve survival for these patients, and enables early detection of other malignancies. This review focuses on the role of CPS in pediatric high grade gliomas (PHGG), the deadliest group of childhood brain tumors. Genetic aspects and clinical features are depicted, allowing clinicians to identify and diagnose these syndromes. Challenges in the management of PHGG in the context of each CPS and the promise of innovative options of treatment and surveillance guidelines are discussed with the hope of improving outcome for individuals with these devastating syndromes.

Pediatric High Grade Gliomas in the Context of Cancer Predisposition Syndromes

Germline mutations in cancer causing genes result in high risk of developing cancer throughout life. These cancer predisposition syndromes (CPS) are especially prevalent in childhood brain tumors and impact both the patient's and other family members' survival. Knowledge of specific CPS may alter the management of the cancer, offer novel targeted therapies which may improve survival for these patients, and enables early detection of other malignancies. This review focuses on the role of CPS in pediatric high grade gliomas (PHGG), the deadliest group of childhood brain tumors. Genetic aspects and clinical features are depicted, allowing clinicians to identify and diagnose these syndromes. Challenges in the management of PHGG in the context of each CPS and the promise of innovative options of treatment and surveillance guidelines are discussed with the hope of improving outcome for individuals with these devastating syndromes.

Secondary Malignancies Developing After Acute Lymphoblastic Leukemia And Its TreatmentWith Constitutional Mismatch Repair Deficiency Syndrome In Siblings.

Background & Objectives: Acute Lymphoblastic Leukemia (ALL) is the most common childhood malignancy, with an annual rate of 3 to 4 cases per 1,00,000 children. ALL patients are treated with chemotherapeutic agents and cranial irradiation. Long-term sequelae of treatment are impaired intellectual and psychomotor functioning, neuroendocrine abnormalitites, impaired reproductive capacity, cardiotoxicity and second malignant neoplasms are being reported with increased frequency in the survivors. Among second neoplasms observed after treatment of ALL, central nervous system (CNS) tumors in patients treated with cranial irradiation are the most common. Others are Lymphoma, Acute Myeloid Leukemia (AML) and Thyroid Cancer. Methodology & Results: We are reporting four cases ,who developed ALL at the age of 8,6,4 and 25 years respectively(among that case 1 & case 2 are siblings) and were treated with chemotherapy and cranial irradiation. They developed Astrocytoma Grade-4 , Alveolar Soft-Part Sarcoma(ASPS) , Anaplastic Large Cell Medulloblastoma & Ewing’s Sarcoma at, 12 , 15, 8, 12 & 26 years of age respectively. Conclusion: Oncologists should make sure about the radiation doses before starting treatment and they should keep CMMR-D as a possibility in pediatric patients with siblings having h/o malignancy.

Constitutional mismatch repair deficiency syndrome: Do we know it.

Constitutional mismatch repair deficiency syndrome is a rare autosomal recessive syndrome caused by homozygous mutations in mismatch repair genes. This is characterized by the childhood onset of brain tumors, colorectal cancers, cutaneous manifestations of neurofibromatosis‑1 like café au lait spots, hematological malignancies, and occasionally other rare malignancies. Here, we would like to present a family in which the sibling had glioblastoma, and the present case had acute lymphoblastic lymphoma and colorectal cancer. We would like to present this case because of its rarity and would add to literature.