Familial hypertrophic cardiomyopathy

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Hypertrophic cardiomyopathy is a heart condition that is characterized by the thickening (hypertrophy) of the heart (cardiac) muscle. This condition is called nonsyndromic hypertrophic cardiomyopathy when it is not associated with signs and symptoms affecting other parts of the body and when it cannot be explained by other causes, such as chronic high blood pressure.

The symptoms of nonsyndromic hypertrophic cardiomyopathy often appear in adolescence or young adulthood, although they can begin at any time throughout life. In most affected individuals, hypertrophy occurs in the interventricular septum, which is the muscular wall that separates the lower left chamber of the heart (the left ventricle) from the lower right chamber (the right ventricle). This thickening of the interventricular septum can obstruct the flow of oxygen-rich blood from the heart, which may cause an abnormal heart sound during a heartbeat (heart murmur).

The features of nonsyndromic hypertrophic cardiomyopathy can vary, even among members of the same family. While some affected individuals have no associated symptoms, others may experience chest pain; shortness of breath, especially during physical activity; or a sensation of fluttering or pounding in the chest (palpitations). Affected individuals may also have episodes of dizziness or fainting (syncope).

Most people with nonsyndromic hypertrophic cardiomyopathy have a normal life expectancy. However, some affected individuals develop an abnormal heart rhythm (arrhythmia) that may be life-threatening. A small number of affected individuals develop heart failure. Although uncommon, people with nonsyndromic hypertrophic cardiomyopathy have an increased risk of sudden death, even if they have no other symptoms of the condition.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Genetic changes that cause disease are called pathogenic variants. Pathogenic variants in one of several genes can cause nonsyndromic hypertrophic cardiomyopathy, but variants in the MYH7 and MYBPC3 genes are the most common genetic cause of this condition.

Many of the genes that are associated with nonsyndromic hypertrophic cardiomyopathy provide instructions for producing proteins that play an important role in the function of cardiac muscle. Many of these proteins are associated with structures called sarcomeres. Sarcomeres, which are the basic units of muscle contraction, are made up of overlapping thick and thin protein filaments. These thick and thin filaments shift so that the thin filaments move past the thick filaments. This movement shortens the sarcomere and contracts the muscle. Regular contractions of cardiac muscle pump blood to the rest of the body.

The protein produced from the MYH7 gene is the major component of the thick filament in sarcomeres. The protein produced from the MYBPC3 gene provides structural support to the thick filament and helps regulate muscle contractions.

Pathogenic variants in the genes that are associated with nonsyndromic hypertrophic cardiomyopathy cause cells to produce proteins that do not function properly. Many of these altered proteins impair the function of the sarcomeres and disrupt cardiac muscle contraction. Researchers do not understand exactly how changes in the genes that are associated with cardiac muscle and sarcomere function lead to the characteristic features of nonsyndromic hypertrophic cardiomyopathy.

Approximately 70 percent of people with nonsyndromic hypertrophic cardiomyopathy do not have a pathogenic variant in one of the genes that is associated with this condition. In these cases, the cause of the condition is unknown. People who have pathogenic variants in the genes that are associated with sarcomere function tend to show signs and symptoms of nonsyndromic hypertrophic cardiomyopathy earlier in life than people in whom no pathogenic variants are detected.

Hypertrophic cardiomyopathy may occur as part of a syndrome that affects other organs and tissues in the body. These forms of the condition are described as "syndromic" and are caused by variants in other genes.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Nonsyndromic hypertrophic cardiomyopathy has different inheritance patterns depending on the specific gene involved. When nonsyndromic hypertrophic cardiomyopathy occurs in multiple family members, it may be called familial hypertrophic cardiomyopathy.

Nonsyndromic hypertrophic cardiomyopathy is typically inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. However, some people who have the altered gene never develop features of the condition. This is known as incomplete penetrance.

Although many individuals with nonsyndromic hypertrophic cardiomyopathy have a parent with the condition, some people have the condition as a result of a new (de novo) variant in a gene that occurs during the formation of reproductive cells (eggs or sperm) in an individual's parent or during early embryonic development.

Some cases of nonsyndromic hypertrophic cardiomyopathy are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a pathogenic variant to cause the disorder. 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.

In rare cases, affected individuals have a pathogenic variant in two or more genes that are associated with the condition. This can lead to more severe signs and symptoms.

When hypertrophic cardiomyopathy is part of a syndrome, it follows the inheritance pattern of that syndrome.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Hypertrophic cardiomyopathy affects approximately 1 in 500 people worldwide. Nonsyndromic hypertrophic cardiomyopathy likely accounts for more than half of all cases.

Which doctor should you see?

The suggested department for discussing Familial hypertrophic cardiomyopathy is Cardiology, with a cardiologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Is the main concern heart structure, rhythm, circulation or another cause?
• Which symptoms should change the timing of follow-up?
• How would a proposed investigation change the care plan?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Familial hypertrophic cardiomyopathy. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.