神经系统疾病

Biallelic Mismatch Repair Deficiency: A Rare and Trouble Genetic Syndrome

Abstract

Diana Ramos*, Catarina Brandao, Catia Sousa and Mario Dinis Ribeiro

Biallelic Mismatch Repair Deficiency (BMMRD) is a rare autosomal recessive disorder characterized by numerous cancers presenting as early as the first decade of life. Biallelic germline mutations in one of four mismatch repair (MMR) genes (MLH1, MSH2, MSH6, or PMS2) cause this devastating disease. Given the rarity of the syndrome, often asymptomatic tumors and overlap with neurofibromatosis-1, diagnosis is frequently unrecognized or delayed. A high degree of clinical awareness is needed to identify new cases. Immunohistochemical assessment of MMR protein expression and analysis of microsatellite instability are the first tools with which to initiate the study of this syndrome in solid malignancies. MMR immunohistochemical shows a hallmark pattern with absence of staining in both neoplastic and non-neoplastic cells for the biallelic mutated gene. We present a unique case of a young boy diagnosed with invasive colon adenocarcinoma and brain tumor, with classical BMMRD features, found to have biallelic pathogenic PMS2 mutations.