Cardiomyopathy: rare genetic cause diagnosed at Sechenov

Cardiomyopathy: rare genetic cause diagnosed at Sechenov

The team of doctors and scientists identified why the patient experienced issues with his heart and offered a spectre of solutions.

Myocardial diseases are among the most difficult ones in cardiology — in terms of diagnosis and treatment. A very common inherited condition that affects the myocardium is hypertrophic cardiomyopathy (HCM), which has a prevalence of approximately 1:200 worldwide. HCM manifests through an unexplained thickness of the interventricular septum and left ventricular (LV) walls, with or without the obstruction of the LV outflow tract, and various arrhythmias. The doctors and scientists from Sechenov University encountered a rare case of mixed progressive hypertrophic and dilated cardiomyopathy in a young patient, who was found to carry an unlikely genetic mutation. This case report has been published in the journal Frontiers in Pharmacology.

The 27-year-old male patient was admitted to the clinic with biventricular heart failure (NYHA class III). Half a year prior to this hospitalisation, he had undergone a thrombectomy. To the best knowledge of the patient and his relatives, there was no family history of cardiac disease or genetic disorders.

Electrocardiography (ECG) showed sinus tachycardia, as well as signs of hypertrophy of both atria and ventricles. Computed tomography (CT) of the heart revealed dilation of the LV chamber and LV myocardial hypertrophy. Magnetic resonance imaging (MRI) with gadolinium enhancement demonstrated that the LV was spherical and severely dilated.

The blood tests showed erythrocytosis, high count of the white blood cells, high haemoglobin level, and an increase in haematocrit, erythropoietin, creatinine, and fibrinogen. At the same time, polymerase chain reaction (PCR) tests detected no viral genomes in the blood. The right ventricular endomyocardial biopsy revealed a combination of pathologically altered cardiomyocytes, productive vasculitis with thrombosis of individual vessels, and small perivascular lymphocytic-macrophage infiltrates.

The key procedure that helped the doctors determine the origin of the disease was whole exome sequencing (WES). Alignment to the human genome and search for sequence variants identified a homozygous deletion in the MyBPC3 gene. The mutation was homozygous in the patient and heterozygous in his mother. This in-frame deletion of 27 base pairs causes the shortening of the cardiac myosin binding protein in the fibronectin III 2 (C7) domain. This variant is classified as likely pathogenic and seems to be the cause of cardiomyopathy.

The patient was offered supportive therapy — prednisolone, bisoprolol, amiodarone, perindopril, furosemide, spironolactone, warfarin, acetylsalicylic acid, and omeprazole. However, half a year later, the patient experienced another acute thrombosis, and within the following 6 months, he received an implantable cardioverter-defibrillator (ICD) and was put on the waiting list for a heart transplant. The case is complicated by the lack of improvement in the patient’s condition and his remote location within Russia, as he has no constant access to his doctors who treated him in Moscow.

This case has been reported by a team of medics and scientists from Sechenov University, Medical Genetics Laboratory at Petrovsky National Research Centre of Surgery (Moscow), and Department of Bioinformatics at the ‘Genetico’ Centre of Genetics and Reproductive Medicine (Moscow).

Read more: Blagova O, et al. Mixed Hypertrophic and Dilated Phenotype of Cardiomyopathy in a Patient With Homozygous In-Frame Deletion in the MyBPC3 Gene Treated as Myocarditis for a Long Time. Front Pharmacol (2020).