MYH7 variants cause complex congenital heart disease

Area of Science:

• Cardiovascular Genetics
• Molecular Cardiology

Background:

• The MYH7 gene encodes sarcomeric beta-myosin heavy chain, a known cause of hypertrophic and dilated cardiomyopathies.
• Heterozygous pathogenic variants in MYH7 have been associated with left ventricular noncompaction cardiomyopathy (LVNC) and congenital heart disease (CHD), including septal defects and Ebstein anomaly.

Observation:

• This study reports on three probands with complex CHD, LVNC, and/or arrhythmias, all found to have MYH7 variants.
• These probands represented 12 affected family members, with documented histories of Ebstein anomaly (4) and LVNC (7).

Findings:

• The findings indicate a wider phenotypic spectrum of MYH7-related CHD than previously recognized.
• MYH7 variants are associated with complex CHD, LVNC, and arrhythmias, extending beyond previously described cardiomyopathies.

Implications:

• MYH7 should be considered in the genetic evaluation of families with multiple affected individuals and complex CHD, particularly when LVNC or arrhythmias are present.
• Further research is needed to fully understand the role of MYH7 in CHD pathogenesis and its complete phenotypic spectrum.