Mutations in several genes have been found to cause left ventricular noncompaction. Mutations in the MYH7 and MYBPC3 genes have been estimated to cause up to 30 percent of cases; mutations in other genes are each responsible for a small percentage of cases. However, the cause of the condition is often unknown.
Most of the genes associated with left ventricular noncompaction, including MYH7 and MYBPC3, provide instructions for making proteins that play a role in the function of structures within muscle fibers called , which are necessary for muscles to tense (contract). Regular contractions of pump blood to the rest of the body. Other genes associated with left ventricular noncompaction are involved in certain signaling pathways, the formation and maintenance of the structural framework (cytoskeleton) of cardiac muscle cells, or regulation of the electrical signals that control the heartbeat.
It is unclear how genetic mutations cause left ventricular noncompaction. During normal development before birth, cardiac muscle gets condensed (compacted), becoming smooth and firm. Mutations in certain genes likely lead to changes in this process, resulting in a left ventricular cardiac muscle that is not compacted but is thick and spongy, leading to left ventricular noncompaction.
Left ventricular noncompaction can also be part of syndromes that affect multiple parts of the body. When left ventricular noncompaction is part of a syndrome, it is caused by mutations in the gene that cause that syndrome. Additionally, left ventricular noncompaction has been found to develop in a small percentage of women during their first pregnancy. In these women, the cause of the condition is unknown but may be influenced by the increased stress that pregnancy puts on the cardiac muscle. In some cases, the cardiac muscle returns to normal following pregnancy and in other cases, the affected women have the varied signs and symptoms of left ventricular noncompaction throughout their lives.