Overlapping Phenotype: Left Ventricular non-Compaction and Hypertrophic Cardiomyopathy

Aim To study the clinical course of the mixed phenotype (hypertrophic cardiomyopathy, HCMP, and left ventricular noncompaction, LVNC); to determine its genetic causes; and to evaluate incidence of cardiovascular complications (CVC) during the follow-up period. Material and methods In screening of 286 patients with HCMP, 8 of them (2.8 %; median age, 41.5 years; 4 men and 4 women) from unrelated families were found to have the mixed phenotype (combination of HCMP and LVNC). For their 10 first-degree relatives, the most frequent phenotype was HCMP without LVNC; however, both isolated LVNC and the mixed phenotype were also observed. Criteria for HCMP and LVNC were confirmed by echocardiography and cardiac magnetic resonance imaging Genotyping was performed by high-throughput sequencing NGT using the TruSight Cardio Sequencing Panel kit. Results Probands with the HCMP+LVNC combination compared to first-degree relatives with isolated HCMP and LVNC were characterized by more pronounced left ventricular dysfunction (ejection fraction, 43.57±7.6 and 53.64±6.51 %, respectively; p<0.001), a higher risk of CVC, and a higher incidence of ventricular tachyarrhythmias (7.9 and 2.2 %, respectively; p<0.01). 11 mutations in 5 genes were found in 8 patients with the mixed phenotype. 72.7 % of mutations were in the MYH7 and MYBPC3 genes that encode the heavy chain of β-myosin and myosin-binding protein C, respectively; however, in some cases, replacements in other genes (DTNA, TGFB2) were also found. Conclusion The mixed phenotype (HCMP and LVNC) is associated with more severe clinical course of the disease and unfavorable CVC.