Parental balanced chromosomal rearrangement leading to major genomic imbalance and an autosomal trisomy resulting in consecutive pregnancy loss: a case report.

Chromosomal aberrations such as parental balanced translocation contribute to a significant proportion of recurrent pregnancy losses. These have extreme genetic implications on the foetus which can either cause physical and/or mental retardation or early death. In this study, we report a unique clinical case of a couple with three consecutive pregnancy losses and we aim to determine the genetic abnormalities causing the miscarriages. Conventional cytogenetic and molecular genetic analysis were performed on the products of conception as well as for the parents. Chromosomal analysis was performed based on the ISCN 2016 guidelines. This was followed by Chromosomal microarray analysis carried out using ISCA consortium probe set (8X60K). Genetic testing for the 1st product of conception was not performed. However, the 2nd and 3rd products of conception indicated an autosomal trisomy 22 and a 3.7 Mb deletion of 2p (cytoband p25.3) along with 13.6 Mb duplication of 16p (cytoband p13.3p13.12), respectively. The paternal karyotype was normal but mother showed a balanced translocation 46,XX,t(2;16)(p25.3;p13.3). This was parallel to the products of conception microarray findings, unbalanced chromosomal abnormality in the foetus. Balanced translocation carriers are susceptible for meiotic nondisjunction processes and early detection of genetic anomalies can be informative to parents trying to conceive. Genetic analysis of the abortus after the 1st loss can be helpful to understand the cause of miscarriage. A combined approach with microarray and karyotyping of the products of conception can be important to determine the specific aberrations in the foetal chromosomes leading to abortion.