Abstract
Objective. To compare the clinical course and outcomes of sarcomeric and RAS-associated hypertrophic cardiomyopathy (HCM) in children with onset at 1 year of age.
Material and methods. Based on the results of a genetic study, 36 patients with mutations in the genes of sarcomeric proteins and the RAS-MAPK signaling pathway were selected. In these groups, a comparative analysis of clinical status, laboratory and instrumental data, as well as outcomes was carried out. The difference between the groups was assessed using biomedical statistics methods.
Results. Seventeen patients (47%) had mutations in the genes of sarcomeric proteins, and 19 (53%) had mutations in the RAS-MAPK signaling pathway. Among sarcomeric mutations, the most common were mutations in the MYH7 gene (58.8%, n = 10), and in the group of RAS-associated HCM – PTPN11 (42.11%, n = 8) and RAF1 (42.11%, n = 8). Children with RASopathies had a high incidence of congenital malformations of organs and systems, as well as congenital heart disease (p < 0.05). Biventricular HCM was detected in 14 (38.9%) children, obstructive form – in 17 (47.2%) patients. Overall survival rate (mean follow-up duration 10 [6.0; 20.0] years) is 83.3% (n = 30). There were 6 deaths (3 in each group). Overall survival rate at 5 years of age among all children was 91.7% [95% CI 96.4–87.1%], at 10 years of age 88.6% [95% CI 93.9–83.2%]. Implantable cardioverter-defibrillator was installed in 4 children with sarcomeric HCM only (23.5%). Myectomy was performed in 9 (25%) children.
Conclusion. The natural history of HCM in children with onset before one year is characterized by high mortality. Children with RASopathies represent a special risk group at an early age.
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About the authors
- Svetlana G. Fetisova, Junior Researcher, Pediatric Cardiologist; ORCID
- Olesya V. Melnik, Cand. Med. Sci., Senior Researcher; ORCID
- Kseniya A. Sitnikova, Resident Physician; ORCID
- Yuliya V. Fomicheva, Laboratory Geneticist; ORCID
- Polina S. Sokolnikova, Laboratory Geneticist; ORCID
- Tatyana L. Vershinina, Head of Pediatric Cardiology and Medical Rehabilitation Department; ORCID
- Olga V. Fedorova, Head of Grant Competition Support Group; ORCID
- Tatyana M. Pervunina, Dr. Med. Sci., Director of Institute of Perinatology and Pediatrics, Chief of Chair of Perinatology and Pediatrics, Institute of Medical Education; ORCID
- Anna A. Kostareva, Dr. Med. Sci., Director of Institute of Molecular Biology and Genetics, Associate Professor of Chair of Internal Medicine, Institute of Medical Education; ORCID
- Elena S. Vasichkina, Dr. Med. Sci., Chief Researcher, Head of Research Center for Unknown, Rare and Genetically Determined Diseases, Professor of Chair of Perinatology and Pediatrics, Institute of Medical Education; ORCID
