Left ventricular noncompaction is a heart (cardiac) muscle disorder that occurs when the lower left chamber of the heart (left ventricle), which helps the heart pump blood, does not develop correctly. Instead of the muscle being smooth and firm, the cardiac muscle in the left ventricle is thick and appears spongy. The abnormal cardiac muscle is weak and has an impaired ability to pump blood because it either cannot completely contract or it cannot completely relax. For the heart to pump blood normally, cardiac muscle must contract and relax fully.

Some individuals with left ventricular noncompaction experience no symptoms at all; others have heart problems that can include sudden cardiac death. Additional signs and symptoms include abnormal blood clots, irregular heart rhythm (arrhythmia), a sensation of fluttering or pounding in the chest (palpitations), extreme fatigue during exercise (exercise intolerance), shortness of breath (dyspnea), fainting (syncope), swelling of the legs (lymphedema), and trouble laying down flat. Some affected individuals have features of other heart defects. Left ventricular noncompaction can be diagnosed at any age, from birth to late adulthood. Approximately two-thirds of individuals with left ventricular noncompaction develop heart failure.

Variants (also known as mutations) in several genes have been found to cause left ventricular noncompaction. Variants in the MYH7 and MYBPC3 genes have been estimated to cause up to 30 percent of cases; variants 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 sarcomeres. These structures are necessary for muscles to tense (contract). Regular contractions of cardiac muscle 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 variants cause left ventricular noncompaction. Normally, during development before birth, cardiac muscle gets condensed (compacted), becoming smooth and firm. Variants in certain genes likely lead to changes in this process. As a result, the left ventricular cardiac muscle 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 variants in the gene involved in 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.

Normal Function

The MYH7 gene provides instructions for making a protein known as the beta (β)-myosin heavy chain. This protein is found in heart (cardiac) muscle and in type I skeletal muscle fibers. (Skeletal muscle are the muscles used for movement.) Type I fibers, which are also known as slow-twitch fibers, are one of two types of fibers that make up skeletal muscles. Type I fibers are the primary component of skeletal muscles that are resistant to fatigue. For example, muscles involved in posture, such as the neck muscles that hold the head steady, are made predominantly of type I fibers.

In cardiac and skeletal muscle cells, the β-myosin heavy chain forms part of a larger protein called type II myosin. Each type II myosin protein consists of two heavy chains (produced from the MYH7 gene) and two pairs of regulatory light chains (produced from several other genes). The heavy chains each have two parts: a head region and a tail region. The head region, called the motor domain, interacts with a protein called actin, which is important for cell movement and shape. The long tail region interacts with other proteins, including the tail regions of other myosin proteins.

Type II myosin generates the mechanical force that is needed for muscles to contract. It is integral to muscle cell structures called sarcomeres, which are the basic units of muscle contraction. Sarcomeres are composed of thick filaments made up of type II myosin and thin filaments made up of actin. The overlapping thick and thin filaments attach to each other and release, which allows the filaments to move relative to one another so that muscles can contract. In the heart, regular contractions of cardiac muscle pump blood to the rest of the body. The coordinated contraction and relaxation of skeletal muscles allow the body to move.

Health Conditions Related to Genetic Changes

Familial hypertrophic cardiomyopathy

Mutations in the MYH7 gene are a common cause of familial hypertrophic cardiomyopathy, accounting for up to 35 percent of all cases. This condition is characterized by thickening (hypertrophy) of the cardiac muscle. Although some people with familial hypertrophic cardiomyopathy have no obvious health effects, all affected individuals have an increased risk of heart failure and sudden death.

Most MYH7 gene mutations that cause familial hypertrophic cardiomyopathy change single protein building blocks (amino acids) in the β-myosin heavy chain protein. The altered protein is likely incorporated into the thick filament, but it may not function properly. It is unclear how MYH7 gene mutations lead to the features of familial hypertrophic cardiomyopathy.

Laing distal myopathy

At least six mutations in the MYH7 gene have been found to cause Laing distal myopathy. This condition causes progressive muscle weakness, particularly affecting the arms and legs. Most of the mutations result in changes in the tail region of the β-myosin heavy chain. Some of these mutations change single amino acids, while others delete a single amino acid from the heavy chain. Changes in the MYH7 gene probably disrupt the normal function of type II myosin in muscle cells. Specifically, researchers suspect that mutations alter the structure of the tail region of the β-myosin heavy chain. The altered tail region may be unable to interact with other proteins, including the tail regions of other myosin proteins. It is unclear how these changes in the structure and function of myosin lead to progressive muscle weakness in people with Laing distal myopathy.

Left ventricular noncompaction

At least 30 MYH7 gene mutations have been found to cause left ventricular noncompaction, which occurs when the lower left chamber of the heart (left ventricle) does not develop correctly. The heart muscle is weakened and cannot pump blood efficiently. These cardiac abnormalities can result in a wide range of outcomes from a complete lack of symptoms to sudden cardiac death. Other signs and symptoms include an irregular heart rhythm (arrhythmia), shortness of breath (dyspnea), and heart failure.

It is unclear how MYH7 gene mutations cause left ventricular noncompaction. During normal development before birth, cardiac muscle gets compacted, becoming smooth and firm. MYH7 gene mutations likely lead to changes in this process, resulting in a left ventricular cardiac muscle that is not compacted but is thick and spongy. This abnormal cardiac muscle is weak and cannot contract effectively, causing the varied signs and symptoms of left ventricular noncompaction.

Myosin storage myopathy

At least six mutations in the MYH7 gene are involved in myosin storage myopathy. This condition causes muscle weakness and is characterized by the formation of protein clumps, which include type II myosin, within type I skeletal muscle fibers. The MYH7 gene mutations that cause myosin storage myopathy change amino acids in the tail region of cardiac β-myosin heavy chain. Researchers suggest that these mutations impair the proper formation of thick filaments. The abnormal proteins accumulate in type I skeletal muscle fibers, forming the protein clumps characteristic of the disorder. It is unclear how the gene mutations lead to muscle weakness in people with myosin storage myopathy.

Congenital fiber-type disproportion

MedlinePlus Genetics provides information about Congenital fiber-type disproportion

Familial dilated cardiomyopathy

MedlinePlus Genetics provides information about Familial dilated cardiomyopathy

Familial restrictive cardiomyopathy

MedlinePlus Genetics provides information about Familial restrictive cardiomyopathy

Other Names for This Gene

• beta-myosin heavy chain
• MGC138376
• MGC138378
• MPD1
• MYH7_HUMAN
• MyHC-beta
• myhc-slow
• MYHCB
• myosin heavy chain (AA 1-96)
• Myosin heavy chain 7
• Myosin heavy chain, cardiac muscle beta isoform
• Myosin, cardiac, heavy chain, beta
• myosin, heavy chain 7, cardiac muscle, beta
• myosin, heavy polypeptide 7, cardiac muscle, beta
• SPMD
• SPMM

Genomic Location

Normal Function

The MYBPC3 gene provides instructions for making cardiac myosin binding protein C (cardiac MyBP-C), which is found in heart (cardiac) muscle cells. In these cells, cardiac MyBP-C is associated with a structure called the sarcomere, which is the basic unit of muscle contraction. Sarcomeres are made up of thick and thin filaments. The overlapping thick and thin filaments attach to each other and release, which allows the filaments to move relative to one another so that muscles can contract. Regular contractions of cardiac muscle pump blood to the rest of the body.

In cardiac muscle sarcomeres, cardiac MyBP-C attaches to thick filaments and keeps them from being broken down prematurely. Cardiac MyBP-C has molecules called phosphate groups attached to it; when the phosphate groups are removed, cardiac MyBP-C is broken down, followed by the breakdown of proteins of the thick filament. Cardiac MyBP-C also regulates how fast muscles contract, although the mechanism is not fully understood.

Health Conditions Related to Genetic Changes

Familial hypertrophic cardiomyopathy

Mutations in the MYBPC3 gene are a common cause of familial hypertrophic cardiomyopathy, accounting for up to 30 percent of all cases. This condition is characterized by thickening (hypertrophy) of the cardiac muscle. Although some people with familial hypertrophic cardiomyopathy have no obvious health effects, all affected individuals have an increased risk of heart failure and sudden death.

MYBPC3 gene mutations that cause familial hypertrophic cardiomyopathy lead to an abnormally short or otherwise altered cardiac MyBP-C protein. It is unknown how these changes cause hypertrophy of the heart muscle.

Left ventricular noncompaction

At least four mutations in the MYBPC3 gene have been found to cause left ventricular noncompaction, which occurs when the lower left chamber of the heart (left ventricle) does not develop correctly. The heart muscle is weakened and cannot pump blood efficiently. These cardiac abnormalities can result in a wide range of outcomes from a complete lack of symptoms to sudden cardiac death. Other signs and symptoms include an irregular heart rhythm (arrhythmia), shortness of breath (dyspnea), and heart failure.

It is unclear how MYBPC3 gene mutations cause left ventricular noncompaction. During normal development before birth, cardiac muscle gets compacted, becoming smooth and firm. MYBPC3 gene mutations likely lead to changes in this process, resulting in a left ventricular cardiac muscle that is not compacted but is thick and spongy. This abnormal cardiac muscle is weak and cannot contract effectively, causing the varied signs and symptoms of left ventricular noncompaction.

Familial dilated cardiomyopathy

MedlinePlus Genetics provides information about Familial dilated cardiomyopathy

Other Names for This Gene

• C-protein, cardiac muscle isoform
• MYBP-C
• myosin-binding protein C, cardiac-type
• MYPC3_HUMAN

Genomic Location

Left ventricular noncompaction can have different inheritance patterns.

In most cases, including when the condition is caused by variants in the MYH7 or MYBPC3 gene, left ventricular noncompaction is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the variant from one affected parent. Other cases result from new variants in the gene and occur in people with no history of the disorder in their family.

Other cases of left ventricular noncompaction are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have variants. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

Left ventricular noncompaction can also be inherited in an X-linked recessive pattern. Some genes associated with this condition (such as the TAFAZZIN gene) are located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a variant would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Left ventricular noncompaction is estimated to affect 8 to 12 per 1 million individuals per year. However, the condition is likely more common than this estimate because individuals who do not have any related signs or symptoms may not come to medical attention.