Laminopathies are rare genetic disorders. They are caused by mutations in the LMNA gene that encodes two proteins: lamin A and C, which are essential for maintaining the structure and function of the cell nucleus.
This genetic disorder causes several diseases, including lamin A/C cardiomyopathy, also known as cardiolaminopathy, which mainly affects the heart and leads to dilation and ventricular dysfunction, often associated with heart rhythm disorders.
Consequences
Cardiomyopathy associated with lamin A/C mutations carry a high risk of heart conduction and heart rhythm disorders: supraventricular tachycardia, atrial fibrillation and ventricular arrhythmias, which can lead to sudden cardiac death.
Causes
Laminopathies are a group of genetic diseases that can occur at any age. They are caused by a mutation in the LMNA gene, which can alter the structure and/or function of A/C lamins, proteins that are essential for maintaining the stability and integrity of the cell nucleus.
The heart and its cells are constantly in motion and exposed to intense mechanical stress. An unstable nucleus is less resistant, resulting in considerable damage to cardiomyocytes. This damage leads to inflammation in the tissues and the formation of scar tissue, which stiffens the heart and impairs its ability to pump blood efficiently.
Another frequent consequence of LMNA gene mutations is dilation of the heart walls. These thin, stretched walls reduce the heart’s ability to pump blood effectively.
Symptoms
Symptoms of cardiolaminopathy vary in terms of their severity and development. However, in general, it first appears in the form of heart rhythm disorders: arrhythmia, bradycardia or tachycardia, fibrillation and heart block (e.g., palpitations, dizziness, shortness of breath, fatigue).
Laminopathy usually results in dilated cardiomyopathy and the associated symptoms: thin heart walls, shortness of breath, fatigue, oedema, palpitations.
At the same time, many patients also have muscle symptoms (weakness) that sometimes precede cardiac symptoms.
Diagnosis
Diagnosis is based on a combination of several medical tests:
- Assessment of medical history and physical examination to assess symptoms and identify a family history. Since this is a genetic disease with high penetrance, it is common for a patient’s family members to be affected as well.
- Echocardiography and/or cardiac MRI are used to assess the size and function of the heart chambers.
- An electrocardiogram (ECG or EKG) detects arrhythmias and any other electrical abnormalities of the heart.
- Genetic tests identify mutations in the LMNA gene.
What is penetrance?
Penetrance of a disease measures the proportion of individuals carrying a specific gene mutation who also exhibit the clinical symptoms of the associated disease. In other words, penetrance measures the likelihood of someone with a genetic mutation developing the signs and symptoms of the disease.
What is an electrocardiogram?
It is a test that records the heart’s electrical activity over a given period of time. It identifies the speed at which the heart is beating (heart rate), whether it is beating normally (heart rhythm) and the effectiveness of the heart muscle. An electrocardiogram is also called an ECG or EKG.
Treatment
Laminopathy treatment is primarily focused on preventing sudden cardiac death. It therefore usually involves implanting a cardioverter-defibrillator. In some cases, it may be combined with the prescription of antiarrhythmics.
Implantable cardioverter-defibrillators continuously monitor the heart rhythm and automatically deliver an electric shock if an abnormal rhythm is detected. The shock helps resynchronize the heartbeat, allowing for effective heart contractions and restoring a regular rhythm.
Finally, patients should regulate their level of physical activity and avoid intense exercise that could accelerate the disease’s progression.
Reviewed and approved by Frédéric Sacher, Professor, MD, PhD, Cardiologist at Bordeaux University Hospital (CHU)
