For Patients

What is it?

Hypertrophic cardiomyopathy is a condition where the heart muscle becomes abnormally thick, making it harder for the heart to pump blood effectively. It is the most common inherited heart condition, affecting approximately 1 in 500 people.

Common Symptoms

• Shortness of breath, especially during exercise
• Chest pain (angina)
• Fatigue
• Palpitations (irregular heartbeats)
• Lightheadedness or fainting (syncope)

Genetic Basis

HCM is typically caused by mutations in genes that encode proteins of the heart muscle (sarcomere). The most commonly affected genes are MYH7 and MYBPC3, but mutations in many other genes can also cause HCM. It is inherited in an autosomal dominant pattern, meaning that children of an affected individual have a 50% chance of inheriting the mutation.

When to Consider Genetic Testing

• If you've been diagnosed with HCM
• If you have a family history of HCM
• If you have a family history of unexplained sudden cardiac death at a young age

What is it?

Vascular Ehlers-Danlos Syndrome is a rare genetic disorder that affects the body's connective tissues, particularly the walls of blood vessels. It makes arteries and organs more fragile and prone to rupture, which can be life-threatening.

Common Symptoms

• Easy bruising
• Thin, translucent skin where veins are clearly visible
• Characteristic facial features (thin lips, small chin, thin nose, large eyes)
• Arterial, intestinal, or uterine fragility
• Joint hypermobility (usually limited to small joints)

Genetic Basis

vEDS is caused by mutations in the COL3A1 gene, which provides instructions for making type III collagen, an important component of connective tissues. It is inherited in an autosomal dominant pattern.

When to Consider Genetic Testing

• If you have clinical features suggestive of vEDS
• If you have a family history of vEDS
• If you have experienced an arterial rupture or dissection at a young age without known risk factors

What is it?

Cardiac amyloidosis is a condition where abnormal proteins called amyloids build up in the heart tissue. This makes the heart stiff and unable to pump blood efficiently, leading to heart failure. ATTR (transthyretin) amyloidosis is a specific type caused by misfolded transthyretin protein.

Common Symptoms

• Shortness of breath
• Fatigue
• Swelling in the legs and ankles
• Irregular heartbeat
• Dizziness or fainting

Genetic Basis

Hereditary ATTR amyloidosis is caused by mutations in the TTR gene. It is inherited in an autosomal dominant pattern. However, there is also a "wild-type" form of ATTR that is not inherited but becomes more common with age.

When to Consider Genetic Testing

• If you've been diagnosed with cardiac amyloidosis
• If you have a family history of ATTR amyloidosis
• If you have unexplained heart failure with preserved ejection fraction, especially if you're over 65

What is it?

Dilated cardiomyopathy (DCM) is a disease of the heart muscle characterized by dilation of the heart chambers, particularly the left ventricle, along with a reduced pumping function (decreased ejection fraction). This leads to heart failure, arrhythmias, and an increased risk of sudden cardiac death. When the condition is genetic in origin, it is referred to as familial DCM (accounting for approximately 20% to 50% of all cases).

Common Symptoms

• Shortness of breath (dyspnea), especially during exertion
• Excessive fatigue
• Swelling of the legs or abdomen (edema)
• Palpitations
• Episodes of fainting or dizziness
• Rapid weight gain due to fluid retention

Genetic Basis

Familial DCM is most commonly inherited in an autosomal dominant pattern. It is caused by mutations in genes that encode proteins of the cardiac cytoskeleton and sarcomere. Frequently implicated genes include LMNA, TTN, DSP, FLNC, DMD, BMD... Notably, mutations in the LMNA gene are particularly associated with a high risk of arrhythmias and sudden cardiac death.

When to Consider Genetic Testing

• If you are diagnosed with DCM, especially at a young age or with no clear cause (e.g., ischemia)
• If you have a family history of DCM or sudden cardiac death
• In the case of unexplained cardiac arrhythmias
• For first-degree relatives of a patient with a known pathogenic mutation

Key Diagnostic Tests

• Echocardiography (to assess ejection fraction)
• Cardiac MRI (to detect myocardial fibrosis)
• ECG and Holter monitoring (to identify arrhythmias)
• Genetic testing
• In selected cases, myocardial biopsy (e.g., fulminant cases or suspected myocarditis)

Sudden Cardiac Death Prevention

An implantable cardioverter-defibrillator (ICD) is recommended for patients with DCM and a left ventricular ejection fraction ≤35%, despite optimal medical therapy. Early ICD implantation may also be considered in carriers of high-risk mutations.

What is it?

Arrhythmogenic Cardiomyopathy (ACM) is an inherited disease of the heart muscle characterized by the progressive loss of cardiac muscle cells (myocytes) and their replacement by fibrous and fatty tissue. It predominantly affects the right ventricle, but may progress to involve both ventricles (biventricular involvement). This pathological remodeling promotes the occurrence of malignant ventricular arrhythmias and increases the risk of sudden cardiac death, especially in young adults and athletes. ACM is considered a disease of intercellular junctions (desmosomes), where genetic mutations lead to cell detachment and disruption of intracellular signaling.

Possible Symptoms

• Palpitations, sometimes sudden and severe
• Syncope (loss of consciousness)
• Chest pain during exertion
• Unexplained sudden cardiac death (often the first manifestation in young individuals)
• May remain asymptomatic for years

Genetic Background

ACM is most often inherited in an autosomal dominant pattern, with variable penetrance and progressive clinical expression. The disease is associated with mutations in genes encoding desmosomal proteins in the heart, including: PKP2 (plakophilin-2), DSP (desmoplakin), DSG2 (desmoglein-2), DSC2 (desmocollin-2), JUP (junction plakoglobin). Other less frequently involved genes: TMEM43, LMNA, DES.

When to Suspect ACM

• Family history of sudden cardiac death before age 35
• Unexplained ventricular arrhythmias
• Abnormal ECG findings (e.g., inverted T waves, epsilon waves, ventricular extrasystoles)
• Right ventricular dilation or dysfunction on imaging
• Patient known to carry a pathogenic genetic mutation

Key Diagnostic Examinations

Diagnosis is based on a composite score (Task Force Criteria) that includes:

• Family and genetic history
• ECG and Holter monitoring abnormalities (e.g., arrhythmias, PVCs)
• Structural or functional abnormalities (detected by cardiac MRI or echocardiography)
• Myocardial biopsy in select cases

Prevention of Sudden Cardiac Death

An ICD is recommended for high-risk patients, such as those with: History of syncope, Sustained ventricular tachycardia, Significant cardiac dysfunction. The decision to implant an ICD is complex and should be personalized, considering genetic, clinical, and electrocardiographic risk factors.