Cardiovascular disease is the number one cause of death around the world. In the US, 1 of every 4 deaths is attributable to cardiovascular disease, and sudden cardiac arrest is the biggest cause of natural death.
While lifestyle, environment and behavior can influence the development of cardiovascular disease, genetics also plays a role. From birth through adulthood, your genes impact every aspect of how the heart forms and functions. A variation in a single gene can increase the risk of heart disease, and understanding these variations can be life-saving. By looking at a patient’s genes, doctors may be able to treat disorders in a more tailored and possibly aggressive manner. In other cases, having the right information can allow for early action that prevents disease from developing or advancing.
With inherited genetic disorders, cardiovascular symptoms can occur in isolation or alongside other symptoms of the syndrome. Symptoms may exist from birth or develop later in life. Patients with inherited cardiovascular disorders may have family histories of sudden death without traditional risk factors. Other patients with genetic conditions may experience noticeable changes to cardiovascular functions without doctors having a clear understanding of the cause.
Examples of Genetic and Inherited Cardiovascular Disorders
Familial hypercholesterolemia (FH) — among the most common inherited cardiac conditions — is believed to occur in 1 out of every 200 to 300 people. FH causes extremely high LDL cholesterol levels, even in adolescence. People with FH are at increased risk for plaque buildup in their arteries and related cardiovascular complications, including heart attack or heart disease, from a young age. In fact, 50% of untreated males with FH experience a cardiac event by age 50. 30% of untreated females have a cardiac event by age 60.
While an estimated 80% of individuals and families with FH remain undiagnosed, genetic testing can provide a definitive molecular diagnosis. The results enable physicians to assess prognosis and risk for patients with the disease. Testing can also inform therapeutic choices and facilitate family cascade testing to identify and treat at-risk relatives. Treating FH early can prevent the development of disease complications and avoid unnecessary premature death.
Cardiomyopathy is a heart muscle disease that impacts how the heart functions, making it difficult to pump blood throughout the body. Cardiomyopathies can be present from birth or develop at a later age.
Inherited cardiomyopathies are a significant cause of sudden cardiac death across all age groups. Patients with an inherited cardiomyopathy are frequently asymptomatic and typically diagnosed incidentally or as a result of family screening.
Hypertrophic cardiomyopathy (HCM) is one of the more common inherited cardiomyopathies. HCM is defined by the presence of increased left and/or right ventricular wall thickness that is not explained by abnormal loading conditions. In some cases, HCM is a result of an inherited metabolic disease. Other types of inherited cardiomyopathies include:
- Congenital cardiac malformations
- Left ventricular noncompaction cardiomyopathy
- Arrhythmogenic right ventricular cardiomyopathy
- Dilated cardiomyopathy
- Restrictive cardiomyopathy
Inherited Cardiac Arrhythmias
Heart rhythm problems are called arrhythmias. Impacting up to 5% of the population, arrhythmias can cause the heart to beat too fast, too slow, or skip beats. While arrhythmias are relatively common, inherited arrhythmias can cause sudden cardiac death in young individuals. Diagnosing presymptomatic patients will enable early treatment that can prevent this sudden loss of life.
Inherited cardiac arrhythmia disorders include:
- Long QT syndrome
- Short QT syndrome
- Catecholaminergic polymorphic ventricular tachycardia
- Brugada syndrome.
Aortopathies are disorders that impact and typically weaken the aorta. Aortopathies are important causes of aortic dilation, aneurysms, dissection, arterial tortuosity or valvular dysfunction. Examples of inherited genetic disorders commonly associated with aortopathies include:
- Marfan syndrome
- Type IV Ehlers-Danlos syndrome
- Loeys–Dietz syndrome
- Aneurysm-osteoarthritis syndrome
- Arterial tortuosity syndrome
- Autosomal dominant polycystic kidney disease
- Turner syndrome
- Familial thoracic aortic aneurysm
- Bicuspid aortic valve
- Fibromuscular dysplasia
Individuals may experience aortopathy in isolation or with syndrome-specific features such as craniofacial dysmorphism, skeletal and joint anomalies, or signs of connective tissue disease.
Genetic Stroke Syndromes
Some individuals are at higher risk for a stroke based on their genes. Genetic stroke syndromes can result from a broad array of genetic or metabolic disorders. These syndromes require treatments beyond standard stroke prevention to reduce morbidity from stroke and other complications of the underlying disease.
Examples of genetic stroke syndromes include:
- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)
- Fabry disease
- Moya-Moya disease
- Retinal vasculopathy with cerebral leukodystrophy
- Cerebral amyloid angiopathy
- Genetic connective tissue diseases
- Sickle-cell disease
- Inherited coagulopathies
Inherited Myopathies with Cardiac Manifestations
An inherited myopathy is an inherited muscle disease that results from a broad array of genetic and metabolic disorders. Many inherited myopathies impact the cardiovascular system, with patients potentially experiencing cardiomyopathies, conduction defects or arrhythmias.
Examples of inherited myopathies with cardiac manifestations include:
- Limb girdle muscular dystrophies (LGMD)
- Emery–Dreifuss muscular dystrophies (EDMD)
- Friedreich ataxia
- Mitochondrial myopathies and cardiomyopathies
- Glycogen storage disorders
- Fatty acid oxidation disorders
- Myotonic dystrophies
When and Why to See a Geneticist
Medical geneticists are medical doctors with advanced training in diagnostic genetic testing as well as in the evaluation and management of rare and genetic diseases. They work closely with genetic counselors, who play an important role in assessing, educating and supporting patients. (Learn more about genetic counseling here.) Seeing a geneticist could help you and your family to experience longer, healthier lives.
According to the American Heart Association (AHA), patients diagnosed with any form of cardiomyopathy, arrhythmic disorders, thoracic aortic aneurysms and dissections, and lipid disorders (such as familial hypercholesterolemia) may be good candidates for genetic counseling and testing. This is especially true if there is a family history of heart problems. If a genetic variant is found, first-degree relatives should also consider genetic testing.
If you’re already seeing a cardiologist, a genetic evaluation may help you learn more about your condition or rule out a genetic cause. Through professional genetic testing and patient evaluation, geneticists can assist cardiologists in diagnosing and managing patients with suspected or confirmed genetic disorders. Working with a geneticist, patients can learn whether their genes have led to an existing heart condition or whether one is likely to develop in the future. Even if you’ve already been diagnosed with an inherited cardiovascular disease, identifying the mutation causing the disease may allow for targeted treatment.
Research in genetics is also rapidly advancing, with discoveries leading to increased treatment options, more strategic use of pharmaceuticals, and an improved ability to recognize and address individual patient risks.
Despite its growing impacts and the decreasing cost of testing, genetics is not a part of standard healthcare. Because many providers are unfamiliar with the field, its benefits and the red flags that may point to a genetic disorder, patients may need to be proactive in asking about seeing a medical geneticist.
If you are interested in diagnostic genetic testing and evaluation, SequenceMD is a medical genetics practice licensed to see patients in Colorado, Wyoming, Arizona, Montana, New Mexico, Kansas and Michigan. We focus on helping adults with undiagnosed conditions and unresolved signs or symptoms as well as on providing care for patients with established genetic and metabolic diagnoses. To learn more and connect with our genetics care team, contact us today.