Cardiomyopathy Panel

Cardiomyopathy is a heart condition with a genetic basis, and early detection allows for appropriate treatment. IntroLab in Belgrade offers a genetic panel for cardiomyopathies, utilizing NGS technology to analyze 173 genes associated with these conditions. This enables accurate diagnosis and a personalized therapeutic approach.

What is cardiomyopathy?

Cardiomyopathies are diseases of the heart muscle that disrupt its normal function. These conditions can cause thickening, enlargement, or scarring of the heart muscle, which may lead to a reduced ability of the heart to pump blood effectively. Cardiomyopathies can be either inherited or acquired and are often linked to serious complications, including heart failure and sudden cardiac death.

What types of cardiomyopathies are there?

There are four main types of cardiomyopathies:

Dilated cardiomyopathy (DCM)

In this type of cardiomyopathy, the left ventricle of the heart becomes enlarged, leading to reduced heart function. Due to the enlargement of the heart chamber, the heart cannot pump blood effectively throughout the body, which can result in heart failure.

DCM can be caused by genetic factors, viral infections, alcoholism, certain medications, and toxic exposures such as chemotherapy. There is also an idiopathic form where the cause is unknown.

Hypertrophic cardiomyopathy (HCM)

This type involves thickening of the heart muscle, most commonly the septum between the left and right ventricles. The thickening can obstruct blood flow out of the heart, which may cause chest pain and fainting, especially during physical activity.

HCM is often an inherited condition caused by mutations in the genes that encode heart muscle proteins. It is typically inherited in an autosomal dominant manner, meaning the disease can occur if only one mutated gene is inherited from one parent.

Restrictive cardiomyopathy (RCM)

The heart muscle becomes stiff and less elastic, making it difficult for the heart to fill with blood between beats. This stiffness of the muscle results in a reduced capacity for the ventricles to fill and decreases blood flow through the heart.

Restrictive cardiomyopathy can be caused by various conditions, including amyloidosis (accumulation of abnormal proteins in tissues), sarcoidosis (an inflammatory disease), hemochromatosis (iron overload), and fibrosis.

Arrhythmogenic cardiomyopathy (ARVC)

In arrhythmogenic cardiomyopathy, the heart muscle, primarily in the right ventricle, is replaced by fatty and fibrous tissue. This can lead to arrhythmias (irregular heartbeats) and, in severe cases, can result in cardiac arrest.

This condition is mostly inherited and is linked to mutations in genes that encode desmosome proteins, which are structures that connect heart muscle cells.

What are the symptoms of cardiomyopathy?

The symptoms of cardiomyopathy can vary depending on the type and severity of the condition.

Dilated cardiomyopathy (DCM):

• Shortness of breath: A feeling of breathlessness, especially during physical activity or when lying down.
• Fatigue: A persistent feeling of exhaustion, even during light activities.
• Swelling: Swelling in the legs, ankles, feet, and abdomen (edema).
• Arrhythmias: Irregular heartbeats, such as rapid or skipped beats.
• Chest pain: Discomfort or pain in the chest, particularly during physical exertion.
• Fainting: Dizziness or loss of consciousness, often due to reduced blood flow to the brain.

Hypertrophic cardiomyopathy (HCM):

• Chest pain: Discomfort or pain, often occurring during physical exertion or stress.
• Fainting: Loss of consciousness, especially after physical exertion or due to an irregular heart rhythm.
• Shortness of breath: A feeling of breathlessness, particularly during exercise.
• Palpitations: Sensation of rapid, irregular, or forceful heartbeats.
• Fatigue: Tiredness, especially following physical activity.
• Sudden death: Unfortunately, HCM can cause sudden cardiac death, often in young athletes.

Restrictive cardiomyopathy (RCM):

• Shortness of breath: Difficulty breathing, especially when lying down or during physical activity.
• Fatigue: A persistent feeling of exhaustion.
• Swelling: Swelling in the legs, ankles, feet, and abdomen.
• Palpitations: Sensations of irregular or rapid heartbeats.
• Fainting: Dizziness or loss of consciousness, often due to reduced blood flow to the brain.

Arrhythmogenic right ventricular cardiomyopathy (ARVC):

• Palpitations: Strong or rapid heartbeats, often caused by arrhythmias.
• Chest pain: Discomfort or pain, especially during physical exertion.
• Fainting: Dizziness or loss of consciousness, often associated with arrhythmias.
• Shortness of breath: A feeling of breathlessness, particularly during physical activity.
• Sudden death: This type of cardiomyopathy can lead to sudden cardiac death, especially in young individuals and athletes.

Why does cardiomyopathy occur?

Cardiomyopathies are often caused by a combination of complex genetic and other factors. To date, over a thousand mutations have been identified in more than 100 genes associated with different types of cardiomyopathies. These genes encode key proteins involved in:

• Heart muscle structure: Proteins of the sarcomere, cytoskeleton, and desmosomes that maintain the stability and functionality of the heart muscle.
• Calcium regulation (Ca2+): Proteins that play a role in managing calcium during heart muscle contraction.
• Energy metabolism: Proteins that influence how heart cells produce and use energy.

In addition to genetic causes, other factors that may contribute to the development of cardiomyopathies include:

• Infections: Viral or bacterial infections that can damage the heart muscle.
• High blood pressure: Prolonged high blood pressure can lead to structural changes in the heart.
• Metabolic disorders: Conditions such as diabetes and thyroid dysfunction.
• Exposure to toxins: Long-term use of alcohol, drugs, or exposure to certain chemicals can negatively affect the heart.

Additionally, some genetic disorders can cause congenital or early-onset forms of cardiomyopathy that appear during childhood.

Benefits of genetic testing for cardiomyopathies

Genetic testing for cardiomyopathies provides:

• Accurate diagnosis: Identifying specific genetic mutations allows for a more precise diagnosis.
• Early detection: Identifies risk in family members who do not yet exhibit symptoms.
• Personalized therapy: Treatment can be tailored to the patient’s specific needs based on their genetic profile.
• Family planning: Helps make informed decisions about future pregnancies.

Who is the cardiomyopathy panel for?

The cardiomyopathy panel is designed for individuals with a family history of heart disease, those diagnosed with cardiomyopathy of unknown cause, and those who have symptoms or are at risk for cardiomyopathies. It can also be beneficial for prenatal testing or for children showing early signs of heart problems.

How many genes does the cardiomyopathy panel test?

The cardiomyopathy panel uses NGS technology to test 173 genes associated with different types of cardiomyopathies. These genes encode proteins that are essential for heart muscle function and are frequently impacted by mutations in individuals with cardiomyopathies.

This panel analyzes the following genes:

AARS2, ABCC6, ABCC9, ACAD9, ACADVL, ACTA1, ACTC1, ACTN2, AGK, AGL, ALMS1, ALPK3, ANO5, APOA1, BAG3, BRAF, CACNA1C, CALR3, CAPN3, CASQ2, CASZ1, CBL, CDH2, CHKB, CHRM2, COX15, CPT2, CRYAB, CSRP3, CTNNA3, DBH, DES, DMD, DNAJC19, DOLK, DPM3, DSC2, DSG2, DSP, DTNA, DYSF, EEF1A2, ELAC2, EMD, EPG5, ETFA, ETFB, ETFDH, FBXL4, FBXO32, FHL1, FHOD3, FKRP, FKTN, FLNC, FOXD4, FOXRED1, FXN, GAA, GATA4, GATA6, GATAD1, GATC, GBE1, GFM1, GLA, GLB1, GMPPB, GSK3B, GTPBP3, GUSB, HADHA, HAND1, HCN4, HFE, HRAS, IDUA, ILK, ISPD, JPH2, JUP, KLHL24, KRAS, LAMA2, LAMP2, LARGE, LDB3, LEMD2, LMNA, LMOD2, LRRC10, LZTR1, MAP2K1, MAP2K2, MAP3K8, MIPEP, MLYCD, MTO1, MYBPC3, MYBPHL, MYH6, MYH7, MYL2, MYL3, MYL4, MYOT, MYPN, MYRF, NDUFAF2, NDUFB11, NEXN, NF1, NKX2-5, NONO, NRAP, NRAS, PCCA, PCCB, PKP2, PLEC, PLEKHM2, PLN, PNPLA2, PPA2, PPCS, PPP1CB, PRDM16, PRKAG2, PTPN11, QRSL1, RAF1, RASA2, RBCK1, RBM20, RIT1, RMND1, RRAS, RYR2, SCN5A, SCNN1B, SCNN1G, SCO1, SCO2, SDHA, SELENON, SGCA, SGCB, SGCD, SGCG, SHOC2, SLC22A5, SLC25A20, SLC25A4, SMCHD1, SOS1, SOS2, SPEG, SPRED1, TAB2, TAZ, TBX20, TBX5, TCAP, TGFB3, TMEM43, TMEM70, TNNC1, TNNI3, TNNI3K, TNNT2, TOR1AIP1, TPM1, TRIM32, TSFM, TTN, TTR, VCL, VCP, VPS13A, XK.

What is the sampling process?

Sampling for genetic testing is typically done using a blood sample. After the sample is collected, DNA is isolated and analyzed to detect any mutations related to cardiomyopathies.

How is cardiomyopathy treated?

Cardiomyopathy treatment varies based on the type and severity of the condition and can involve several strategies. Medications like beta-blockers, ACE inhibitors, and diuretics are commonly prescribed to manage symptoms and lower the risk of complications. In some instances, devices such as pacemakers or defibrillators are necessary to help regulate heart rhythm.

For more severe cases, surgical options, including procedures to repair or replace damaged heart tissue or even heart transplants, may be needed. Additionally, lifestyle changes, including avoiding alcohol, quitting smoking, maintaining a healthy diet, and engaging in regular physical activity, are crucial for managing the condition and preventing further heart damage.

Genetic panels offered by IntroLab

IntroLab offers comprehensive genetic tests for identifying hereditary disorders and genetic diseases:

• Autoinflammatory disease panel
• Arrhythmia panel
• Marfan syndrome panel
• Epilepsy panel
• Clinical exome sequencing
• Molecular karyotyping

These panels are specifically designed to provide accurate and detailed information, which is crucial for diagnosis and personalized treatment.

Prenatal testing

IntroLab offers a variety of prenatal tests for pregnant women, allowing early detection of chromosomal and genetic abnormalities:

• Prenatal BASIC Test
• Prenatal PLUS Test
• Prenatal EXPERT Test
• Prenatal PREMIUM Test
• Prenatal SPECIAL Test
• Prenatal SPECIAL + SMA Test

These tests provide parents and healthcare professionals with valuable information about fetal health during pregnancy.