The significance of genetic verification of the diagnosis for children with a dilated phenotype of cardiomyopathy with non-compact myocardium and increased trabecularity

Abstract

Purpose: to compare the course of the disease in the dilated phenotype of cardiomyopathy with a non-compact myocardium and increased trabecularity, verify the molecular genetic diagnosis using the new generation sequencing method, and study the segregation of nucleotide variants in families. Materials and methods. The study included 50 patients, divided into two groups: 27 patients with a dilated phenotype of cardiomyopathy and non-compact myocardium and 23 patients with a dilated phenotype and increased trabecularity. Changes in the laboratory and instrumental parameters, events and outcomes were analyzed. The massively parallel sequencing of a panel of genes developed at the National Medical Research Center of Children’s Health of the Ministry of Health of the Russian Federation (81 genes) was applied. For data processing, the IBM SPSS Statistics 24.0 application package was used for bioinformatic analysis and assessment of the pathogenicity of the identified nucleotide variants, the Russian guidelines for interpreting human DNA nucleotide data, Alamut software and the HGMD Professional database were used. Results. Following a year of therapy for chronic heart failure in DF CMP patients, the content of terminal natriuretic peptide in the blood of patients with increased trabecularity was found to decline significantly. In patients in both groups, myocardial contractility improved and left ventricular end-diastolic size decreased. Significant nucleotide variants when using the cardiopanel were verified in 85% of cases in patients with non-compact myocardium and 91% in patients with increased trabecularity. At the same time, predictors of poor prognosis and severe course of cardiomyopathy were identified - pathogenic variants c.2647G>A in the MYH7 gene, c.688G>A in the TPM1 gene, c.2350C> T in the CACNA1C gene. In one clinical case, when laminopathy was detected, a cardioverter-defibrillator was installed as prophylaxis for sudden death. In addition, 18 families were examined, 3 cases of de novo mutation were identified, confirming the high frequency of asymptomatic and low-symptom carriers of nucleotide variants. Conclusion. The determination of the molecular and genetic cause of the dilated cardiomyopathy phenotype allows optimizing the management tactics of sick children. Furthermore, the identification of family segregation of mutations with the identification of carriers ensures timely monitoring by specialists.