Cardiovascular Genetic Testing - Hereditary Heart and Vascular Disease

Last Literature Review: October 2021 Last Update:

Genetics plays a role in many cardiovascular complications. The field of cardiovascular genetics focuses on genetic contributions to cardiovascular disease and genetic syndromes that may cause cardiovascular complications. Laboratory testing to determine the presence of disease-causing genetic variants can inform diagnosis, guide treatment decisions, and determine a patient’s individual risk for cardiovascular complications. This topic provides a broad overview of laboratory testing in cardiovascular genetics and discusses cardiomyopathiesarrhythmiasvascular malformations, and other genetic syndromes with cardiovascular involvement.

Laboratory Testing

There are several types of laboratory tests that may be useful in evaluating potential cardiovascular genetic disorders. The first is single gene (or single variant) testing. This type of test is appropriate when a specific condition or syndrome is suspected or when there is a known family history of a particular genetic variant. The second type is panel testing. A panel test examines many genes and detects variants that may cause certain diseases. Panel tests may be appropriate when many variants are associated with a particular disease or symptom (eg, arrythmia). Finally, whole exome or genome sequencing can be performed to examine all of the genes (exome sequencing) and DNA (genome sequencing) for variants that may explain disease or may indicate an increased risk for future illness. Broader sequencing may be appropriate when patients have a complex medical history or when specific diseases or mutations are not suspected.

Cardiovascular Genetic Disease

Cardiomyopathy and Arrythmias

Inherited cardiomyopathy and arrythmias are genetically and phenotypically heterogeneous, and panel testing may be appropriate when clinical presentation and family history do not indicate a particular disease or syndrome. Genetic cardiomyopathies include dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), and left ventricular noncompaction cardiomyopathy (LVNC). Inherited arrhythmic disorders are caused by mutations in ion channel-encoding genes and include long QT syndrome (LQTS), short QT syndrome (SQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and Brugada syndrome (BrS). Diagnosis of these conditions is generally based on clinical presentation, patient history, electrocardiographic examination, and genetic analysis.

Vascular Malformations and Vasculopathies

Vascular malformation syndromes are caused by defects of blood vessels, which can affect venous, arterial, capillary, and combined types of blood vessels. Genetic-related vascular malformation disorders include capillary malformation-arteriovenous malformation (CM-AVM), hereditary hemorrhagic telangiectasia (HHT), pulmonary arterial hypertension (PAH), cerebral cavernous malformation (CCM), glomuvenous malformation, and multiple cutaneous and mucosal venous malformations. If no single specific diagnosis is strongly suspected, a panel test can confirm clinical diagnosis of a genetic-related vascular malformation disorder. Genetic testing is also useful to confirm clinical diagnoses of vasculopathies such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

Familial Lipid Disorders

Familial lipid disorders are characterized by elevated levels of cholesterol and an increased risk for cardiovascular disease. Inherited lipid disorders include familial hypercholesterolemia and APOE-related heart disease. Genetic testing may be useful to determine the risk of cardiovascular complications, particularly in families with a history of heart disease.

Hereditary Syndromes Associated With Cardiovascular Disease

There are many hereditary syndromes that are associated with cardiovascular disease. These include neuromuscular disorders such as Duchenne muscular dystrophyBecker muscular dystrophyEmery-Dreifuss muscular dystrophymyotonic dystrophy, and Barth syndrome. There are also genetic syndromes and conditions associated with aortopathy, including Marfan syndrome (MFS), thoracic aortic aneurysm and dissection (TAAD), Ehlers-Danlos syndrome, homocystinuria, Loeys-Dietz syndrome, congenital contractural arachnodactyly (CCA), and Turner syndrome. Other hereditary conditions associated with heart disease include familial transthyretin (TTR) amyloidosis and primary carnitine deficiency.

Other Genetic Conditions That Affect the Cardiovascular System

Laterality defects, such as heterotaxy and situs inversus, are developmental defects characterized by the abnormal placement of the abdominal (visceral) organs. These defects can also impact the left-right symmetry in the heart. Genetic testing is used to detect variants in genes known to cause laterality defects such as situs inversus, heterotaxy, and other related complex congenital heart defects.

Medical Experts



Rong Mao, MD, FACMG
Professor of Pathology (Clinical), and Co-Director of Laboratory Genetics and Genomics Fellowship, University of Utah
Medical Director, Molecular Genetics and Genomics, ARUP Laboratories