CMMRD-associated embryonic rhabdomyosarcoma in a child. Clinical case with literature review

Abstract

Introduction. Hereditary disorders in the DNA repair system can lead to the development of malignant neoplasms in childhood. DNA constitutional mismatch repair deficiency syndrome (CMMRD) is a very rare genetic autosomal recessive disorder caused by homozygous mutations in one of the four mismatch repair genes (MLH1, MSH2, MSH6, and PMS2). The frequency of occurrence is 0.0000001 of the adult and child population. For now about 150 observations have been published in the world literature. The prognosis for CMMRD syndrome is extremely unfavorable. The spectrum of tumors that make up the CMMRD syndrome is very wide, and includes mainly malignant brain tumors, tumors of the digestive tract, hematological malignancies, embryonic tumors, all of which develop in childhood.The purpose of the study is to report a case of CMMRD-associated embryonic rhabdomyosarcoma in a 3-year-old child.Conclusions. A review of the literature and the clinical case we have described show that rhabdomyosarcoma belongs to the tumor spectrum of the CMMRD syndrome. An immunohistochemical study revealed an isolated loss of PMS2 gene expression. Taking into account the clinical course of the CMMRD syndrome, a thorough study of the family history in patients with rhabdomyosarcoma is recommended, as well as a molecular genetic study, including the search for germinal mutations in genes in the DNA repair system and the assessment of microsatellite instability in the material of the tumor tissue. The clinical symptoms of CMMRD syndrome are nonspecific and depend on the morphological variant of the primary tumor. Distinctive molecular genetic features of this syndrome are: homozygous mutations with loss of function of the germline genes of the MMR system (mismatch repair) (MLH1, MSH2, MSH6 or PMS2).