MedGen

An autosomal dominant condition caused by mutation(s) in the KCNQ1 gene, encoding potassium voltage-gated channel subfamily KQT member 1. It is characterized by a prolonged QT interval that may result in torsade de pointes, ventricular fibrillation and/or sudden cardiac death. [from NCI]

Brugada syndrome is characterized by cardiac conduction abnormalities (ST segment abnormalities in leads V1-V3 on EKG and a high risk for ventricular arrhythmias) that can result in sudden death. Brugada syndrome presents primarily during adulthood, although age at diagnosis may range from infancy to late adulthood. The mean age of sudden death is approximately 40 years. Clinical presentations may also include sudden infant death syndrome (SIDS; death of a child during the first year of life without an identifiable cause) and sudden unexpected nocturnal death syndrome (SUNDS), a typical presentation in individuals from Southeast Asia. Other conduction defects can include first-degree AV block, intraventricular conduction delay, right bundle branch block, and sick sinus syndrome. [from GeneReviews]

Emery-Dreifuss muscular dystrophy (EDMD) is characterized by the clinical triad of: joint contractures that begin in early childhood; slowly progressive muscle weakness and wasting initially in a humero-peroneal distribution that later extends to the scapular and pelvic girdle muscles; and cardiac involvement that may manifest as palpitations, presyncope and syncope, poor exercise tolerance, and congestive heart failure along with variable cardiac rhythm disturbances. Age of onset, severity, and progression of muscle and cardiac involvement demonstrate both inter- and intrafamilial variability. Clinical variability ranges from early onset with severe presentation in childhood to late onset with slow progression in adulthood. In general, joint contractures appear during the first two decades, followed by muscle weakness and wasting. Cardiac involvement usually occurs after the second decade and respiratory function may be impaired in some individuals. [from GeneReviews]

Nonfamilial hypertrophic cardiomyopathy tends to be milder. This form typically begins later in life than familial hypertrophic cardiomyopathy, and affected individuals have a lower risk of serious cardiac events and sudden death than people with the familial form.

While most people with familial hypertrophic cardiomyopathy are symptom-free or have only mild symptoms, this condition can have serious consequences. It can cause abnormal heart rhythms (arrhythmias) that may be life threatening. People with familial hypertrophic cardiomyopathy have an increased risk of sudden death, even if they have no other symptoms of the condition. A small number of affected individuals develop potentially fatal heart failure, which may require heart transplantation.

The symptoms of familial hypertrophic cardiomyopathy are variable, even within the same family. Many affected individuals have no symptoms. Other people with familial hypertrophic cardiomyopathy may experience chest pain; shortness of breath, especially with physical exertion; a sensation of fluttering or pounding in the chest (palpitations); lightheadedness; dizziness; and fainting.

In familial hypertrophic cardiomyopathy, cardiac thickening usually occurs in the interventricular septum, which is the muscular wall that separates the lower left chamber of the heart (the left ventricle) from the lower right chamber (the right ventricle). In some people, thickening of the interventricular septum impedes the flow of oxygen-rich blood from the heart, which may lead to an abnormal heart sound during a heartbeat (heart murmur) and other signs and symptoms of the condition. Other affected individuals do not have physical obstruction of blood flow, but the pumping of blood is less efficient, which can also lead to symptoms of the condition. Familial hypertrophic cardiomyopathy often begins in adolescence or young adulthood, although it can develop at any time throughout life.

Hypertrophic cardiomyopathy is a heart condition characterized by thickening (hypertrophy) of the heart (cardiac) muscle. When multiple members of a family have the condition, it is known as familial hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy also occurs in people with no family history; these cases are considered nonfamilial hypertrophic cardiomyopathy.  [from MedlinePlus Genetics]

Andersen-Tawil syndrome (ATS) is characterized by a triad of: episodic flaccid muscle weakness (i.e., periodic paralysis); ventricular arrhythmias and prolonged QT interval; and anomalies including low-set ears, widely spaced eyes, small mandible, fifth-digit clinodactyly, syndactyly, short stature, and scoliosis. Affected individuals present in the first or second decade with either cardiac symptoms (palpitations and/or syncope) or weakness that occurs spontaneously following prolonged rest or following rest after exertion. Mild permanent weakness is common. Mild learning difficulties and a distinct neurocognitive phenotype (i.e., deficits in executive function and abstract reasoning) have been described. [from GeneReviews]

The clinical manifestations of CACNA1C-related disorders include a spectrum of nonsyndromic and syndromic phenotypes, which generally correlate with the impact of the pathogenic variant on calcium current. Phenotypes can include nonsyndromic long QT syndrome (rate-corrected QT [QTc] interval >480 ms); nonsyndromic short QT syndrome (QTc <350 ms), with risk of sudden death; Brugada syndrome (ST segment elevation in right precordial leads [V1-V2]) with short QT interval; classic Timothy syndrome (prolonged QT interval, autism, and congenital heart defect) with or without unilateral or bilateral cutaneous syndactyly variably involving fingers two (index), three (middle), four (ring), and five (little) and bilateral cutaneous syndactyly of toes two and three; and CACNA1C-related neurodevelopmental disorder, in which the features tend to favor one or more of the following: developmental delay / intellectual disability, hypotonia, epilepsy, and/or ataxia. [from GeneReviews]

Congenital long QT syndrome is electrocardiographically characterized by a prolonged QT interval and polymorphic ventricular arrhythmias (torsade de pointes). These cardiac arrhythmias may result in recurrent syncope, seizure, or sudden death (Jongbloed et al., 1999). For a discussion of genetic heterogeneity of long QT syndrome, see LQT1 (192500). [from OMIM]

Jervell and Lange-Nielsen syndrome (JLNS) is characterized by congenital profound bilateral sensorineural hearing loss and long QTc, usually >500 msec. Prolongation of the QTc interval is associated with tachyarrhythmias, including ventricular tachycardia, episodes of torsade de pointes ventricular tachycardia, and ventricular fibrillation, which may culminate in syncope or sudden death. Iron-deficient anemia and elevated levels of gastrin are also frequent features of JLNS. The classic presentation of JLNS is a deaf child who experiences syncopal episodes during periods of stress, exercise, or fright. Fifty percent of individuals with JLNS had cardiac events before age three years. More than half of untreated children with JLNS die before age 15 years. [from GeneReviews]

Danon disease is a multisystem condition with predominant involvement of the heart, skeletal muscles, and retina, with overlying cognitive dysfunction. Males are typically more severely affected than females. Males usually present with childhood onset concentric hypertrophic cardiomyopathy that is progressive and often requires heart transplantation. Rarely, hypertrophic cardiomyopathy can evolve to resemble dilated cardiomyopathy. Most affected males also have cardiac conduction abnormalities. Skeletal muscle weakness may lead to delayed acquisition of motor milestones. Learning disability and intellectual disability, most often in the mild range, are common. Additionally, affected males can develop retinopathy with subsequent visual impairment. The clinical features in females are broader and more variable. Females are more likely to have dilated cardiomyopathy, with a smaller proportion requiring heart transplantation compared to affected males. Cardiac conduction abnormalities, skeletal muscle weakness, mild cognitive impairment, and pigmentary retinopathy are variably seen in affected females. [from GeneReviews]

Congenital long QT syndrome is electrocardiographically characterized by a prolonged QT interval and polymorphic ventricular arrhythmias (torsade de pointes). These cardiac arrhythmias may result in recurrent syncope, seizure, or sudden death (Jongbloed et al., 1999). For a discussion of genetic heterogeneity of long QT syndrome, see LQT1 (192500). [from OMIM]

Mutations in the PRKAG2 gene (602743) give rise to a moderate, essentially heart-specific, nonlysosomal glycogenosis with clinical onset typically in late adolescence or in the third decade of life, ventricular pre-excitation predisposing to supraventricular arrhythmias, mild to severe cardiac hypertrophy, enhanced risk of sudden cardiac death in midlife, and autosomal dominant inheritance with full penetrance (summary by Burwinkel et al., 2005). [from OMIM]

Brugada syndrome is characterized by cardiac conduction abnormalities (ST segment abnormalities in leads V1-V3 on EKG and a high risk for ventricular arrhythmias) that can result in sudden death. Brugada syndrome presents primarily during adulthood, although age at diagnosis may range from infancy to late adulthood. The mean age of sudden death is approximately 40 years. Clinical presentations may also include sudden infant death syndrome (SIDS; death of a child during the first year of life without an identifiable cause) and sudden unexpected nocturnal death syndrome (SUNDS), a typical presentation in individuals from Southeast Asia. Other conduction defects can include first-degree AV block, intraventricular conduction delay, right bundle branch block, and sick sinus syndrome. [from GeneReviews]

Any familial isolated dilated cardiomyopathy in which the cause of the disease is a mutation in the SCN5A gene. [from MONDO]

Atrial fibrillation (AF) is the most common sustained cardiac rhythm disturbance, affecting more than 2 million Americans, with an overall prevalence of 0.89%. The prevalence increases rapidly with age, to 2.3% between the ages of 40 and 60 years, and to 5.9% over the age of 65. The most dreaded complication is thromboembolic stroke (Brugada et al., 1997). For a discussion of genetic heterogeneity of atrial fibrillation, see 608583. [from OMIM]

An autosomal dominant subtype of familial hypertrophic cardiomyopathy caused by mutation(s) in the ACTC1 gene, encoding actin, alpha cardiac muscle 1. [from NCI]

Any familial isolated arrhythmogenic right ventricular dysplasia in which the cause of the disease is a mutation in the DSC2 gene. [from MONDO]

Congenital long QT syndrome is electrocardiographically characterized by a prolonged QT interval and polymorphic ventricular arrhythmias (torsade de pointes). These cardiac arrhythmias may result in recurrent syncope, seizure, or sudden death (Jongbloed et al., 1999). For a discussion of genetic heterogeneity of long QT syndrome, see LQT1 (192500). [from OMIM]

Progressive familial heart block type I (PFHBI, PFHB1) is an autosomal dominant cardiac bundle branch disorder that may progress to complete heart block (Brink and Torrington, 1977; van der Merwe et al., 1986; van der Merwe et al., 1988). It is defined on electrocardiogram by evidence of bundle branch disease, i.e., right bundle branch block, left anterior or posterior hemiblock, or complete heart block, with broad QRS complexes. Progression has been shown from a normal electrocardiogram to right bundle branch block and from the latter to complete heart block. These electrocardiographic features differentiate PFHB type I from progressive familial heart block type II (PFHBII, PFHB2; 140400), in which the onset of complete heart block is associated with narrow complexes. Electrocardiographically the changes represent, respectively, bundle branch disease (PFHB1) and atrioventricular nodal disease with an atrioventricular block and an idionodal escape rhythm (PFHB2). PFHBI is manifested symptomatically when complete heart block supervenes, either with dyspnea, syncopal episodes, or sudden death. Treatment, which is best managed by regular electrocardiographic follow-up, is by the timely implantation of a pacemaker (Brink et al., 1995). Genetic Heterogeneity of Progressive Familial Heart Block Type I Progressive familial heart block type IB (PFHB1B; 604559) is caused by mutation in the TRPM4 gene (606936) on chromosome 19q13.32. [from OMIM]

Jervell and Lange-Nielsen syndrome (JLNS) is characterized by congenital profound bilateral sensorineural hearing loss and long QTc, usually >500 msec. Prolongation of the QTc interval is associated with tachyarrhythmias, including ventricular tachycardia, episodes of torsade de pointes ventricular tachycardia, and ventricular fibrillation, which may culminate in syncope or sudden death. Iron-deficient anemia and elevated levels of gastrin are also frequent features of JLNS. The classic presentation of JLNS is a deaf child who experiences syncopal episodes during periods of stress, exercise, or fright. Fifty percent of individuals with JLNS had cardiac events before age three years. More than half of untreated children with JLNS die before age 15 years. [from GeneReviews]

Brugada syndrome is characterized by cardiac conduction abnormalities (ST segment abnormalities in leads V1-V3 on EKG and a high risk for ventricular arrhythmias) that can result in sudden death. Brugada syndrome presents primarily during adulthood, although age at diagnosis may range from infancy to late adulthood. The mean age of sudden death is approximately 40 years. Clinical presentations may also include sudden infant death syndrome (SIDS; death of a child during the first year of life without an identifiable cause) and sudden unexpected nocturnal death syndrome (SUNDS), a typical presentation in individuals from Southeast Asia. Other conduction defects can include first-degree AV block, intraventricular conduction delay, right bundle branch block, and sick sinus syndrome. [from GeneReviews]