MYH7 variants cause complex congenital heart disease

• Published in: American journal of medical genetics. Part A 2022-09, Vol.188 (9), p.2772-2776
• Main Authors: Ritter, Alyssa, Leonard, Jacqueline, Gray, Christopher, Izumi, Kosuke, Levinson, Katharine, Nair, Divya R., O'Connor, Matthew, Rossano, Joseph, Shankar, Venkat, Chowns, Jessica, Marzolf, Amy, Owens, Anjali, Ahrens‐Nicklas, Rebecca C.
• Format: Article
• Language: English
• Subjects: Arrhythmias, Cardiac - complications; Arrhythmias, Cardiac - genetics; Cardiac arrhythmia; Cardiac Myosins - genetics; Cardiomyopathies - etiology; Cardiomyopathy; Cardiovascular disease; Congenital diseases; congenital heart disease; Congestive heart failure; Coronary artery disease; Dilated cardiomyopathy; Ebstein Anomaly; Heart Defects, Congenital - complications; Heart Defects, Congenital - genetics; Heart diseases; heart failure; Humans; Mutation; MYH7; Myosin; Myosin Heavy Chains - genetics; noncompaction; Ventricle
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.62766

MYH7, encoding the myosin heavy chain sarcomeric β‐myosin heavy chain, is a common cause of both hypertrophic and dilated cardiomyopathy. Additionally, families with left ventricular noncompaction cardiomyopathy (LVNC) and congenital heart disease (CHD), typically septal defects or Ebstein anomaly, have been identified to have heterozygous pathogenic variants in MHY7. One previous case of single ventricle CHD with heart failure due to a MYH7 variant has been identified. Herein, we present a single center's experience of complex CHD due to MYH7 variants. Three probands with a history of CHD, LVNC, and/or arrhythmias were identified to have MYH7 variants through multigene panel testing or exome sequencing. These three patients collectively had 12 affected family members, four with a history of Ebstein anomaly and seven with a history of LVNC. These findings suggest a wider phenotypic spectrum in MYH7‐related CHD than previously understood. Further investigation into the possible role of MYH7 in CHD and mechanism of disease is necessary to fully delineate the phenotypic spectrum of MYH7‐related cardiac disease. MYH7 should be considered for families with multiple individuals with complex CHD in the setting of a family history of LVNC or arrhythmias.