Case Report of Severe Dilatative Cardiomyopathy Caused by a Novel Mutation in Cardiac Beta-Myosin

Background: Dilatative cardiomyopathy (DCM) manifests by pathological enlargement of the heart, compromising its function to pump blood effectively. Several genes, including MYH7, have been described for inherited forms. The high prevalence of de novo mutations emphasizes that genetic screening is also indicated in cases of sporadic cardiomyopathy. Therefore, it is becoming even more important to describe phenotypes in de novo mutations

Method: The molecular basis was identified using trio whole-exome next-generation sequencing.

Results: We describe a female patient with a severe phenotype of DCM resulting in palliative care. Her parents were nonrelated and displayed no symptoms of the disease. The patient was critically ill in the postneonatal period with clinical signs of low cardiac output until death. During the time observed, there was no improvement in ventricular function, and stable hemodynamics could only be achieved with catecholamine therapy and mechanical ventilation. Other causes for reduced cardiac function (myocarditis, mitochondrial, or metabolic disease) were excluded. The gold standard for the diagnosis of cardiomyopathy is myocardial biopsy. However, especially in critically ill children, biopsy cannot be performed, without the risk of complications, highlighting the importance of genetics in clinical decision-making. In our patient, we identified a heterozygous de novo missense-variant in the motor domain region of the MYH7 gene (NM_000257.4):c.1180G > Ap.(Asp394Asn). Missense variants are a typical cause of MYH7-associated cardiomyopathies. This variant has not been described in the literature and is not recorded in the gnomAD population database. In ClinVar, it has been described three times as a variant of unknown significance [VCV000042828.4]. In one of those reports, MYH7 has been associated with two cases of de novo missense variates in (1) an infant-onset left ventricular non-compaction cardiomyopathy (LVNC) and DCM in a Caucasian patient, and (2) a neonate of unspecified ancestry with LVNC. Another missense variant, causing a different amino acid exchange at the same MYH7 residue, has been classified as likely pathogenic. Thus, we classified this variant as likely pathogenic (revised MYH7 ACMG criteria [PMID: 29300372]: PS2, PM1, PM2, and PP3).

Conclusion: We report the combination of de novo missense-variant in MYH7 Gen c.1180G > A p.(Asp394Asn) and severe DCM. The clinical severity did not allow myocardial biopsy, highlighting the importance of genetic findings for treatment decisions in the clinical routine.

Publication History

Article published online:
12 February 2022