Nonsyndromic dilated cardiomyopathy

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Dilated cardiomyopathy is a form of heart disease in which the heart (cardiac) muscle becomes thin and enlarged (dilated). The dilation, which typically starts in the lower left chamber of the heart (left ventricle), makes it harder for the heart to pump blood to the rest of the body.

Dilated cardiomyopathy is called nonsyndromic dilated cardiomyopathy when it cannot be explained by other causes, such as a heart attack or damage to the valves of the heart, and is not associated with signs and symptoms that affect other parts of the body.

The signs and symptoms of nonsyndromic dilated cardiomyopathy vary among affected individuals, even among members of the same family. The signs and symptoms typically begin in mid-adulthood, but they can occur at any time from infancy to late adulthood. Affected individuals may have a sensation of fluttering or pounding in the chest (palpitations); shortness of breath, especially when lying down or during physical activity; fatigue; and swelling of the legs and feet. Affected individuals may also have episodes of dizziness or fainting (syncope).

Over time, people with nonsyndromic dilated cardiomyopathy may develop life-threatening complications, which can include abnormal heart rhythms (arrhythmias) and heart failure. Although uncommon, sudden death can occur in people with nonsyndromic dilated cardiomyopathy, even if they have no other symptoms of the condition.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Variants (also called mutations) in more than 20 genes have been found to cause nonsyndromic dilated cardiomyopathy. These genes provide instructions for making proteins that are found in cardiac muscle cells called cardiomyocytes.

Many of these proteins play important roles in the tensing (contraction) of the cardiac muscle through their association with structures called sarcomeres. Sarcomeres are made of proteins that generate the mechanical force needed for muscles to contract; they are the basic units of contraction. Other proteins that are associated with nonsyndromic dilated cardiomyopathy make up the structural framework (the cytoskeleton) of cardiomyocytes. The remaining proteins have various roles within cardiomyocytes to ensure that these cells function properly.

A genetic cause is found in approximately 25 to 35 percent of people with dilated cardiomyopathy. A genetic cause is more likely to be found in individuals who have affected family members.

Variants in one gene, TTN, account for approximately 15 to 20 percent of all cases of dilated cardiomyopathy. The TTN gene provides instructions for making a protein called titin, which is found in the sarcomeres of cardiomyocytes and other muscle cells. Titin provides structure, flexibility, and stability to sarcomeres. Titin also plays a role in chemical signaling and in the assembly of new sarcomeres. Many of the TTN gene variants in people with nonsyndromic dilated cardiomyopathy cause cells to produce an abnormally short version of the titin protein. The altered protein likely impairs sarcomere function and disrupts chemical signaling.

Dilated cardiomyopathy may also 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.

Some cases of dilated cardiomyopathy are acquired during a person’s lifetime. Causes of acquired dilated cardiomyopathy can include damage to the valves that control the flow of blood through the heart and damage to the cardiac muscle that is caused by a heart attack, infections, or certain medications.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Nonsyndromic dilated cardiomyopathy has different inheritance patterns depending on the specific gene involved. When nonsyndromic dilated cardiomyopathy is present in multiple family members, it is often called familial dilated cardiomyopathy.

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

Although many individuals with nonsyndromic dilated cardiomyopathy have an affected parent, some cases of this condition result from new (de novo) variants in a gene that occur during the formation of reproductive cells (eggs or sperm) in an affected individual's parent or during early embryonic development.

Nonsyndromic dilated cardiomyopathy can also be inherited in an autosomal recessive pattern, which means both copies of a gene in each cell must have a 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.

Syndromic dilated cardiomyopathy follows the inheritance pattern of the associated syndrome.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Dilated cardiomyopathy may affect as many as 1 in 250 people. In approximately 30 to 50 percent of these cases, there is a family history of the condition.

Which doctor should you see?

The suggested department for discussing Nonsyndromic dilated 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 Nonsyndromic dilated 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.