The individual cells of the heart communicate with each other with electrical signals, and these electrical signals are disrupted in those with<unk> . As a genetic condition, the syndrome is ultimately caused by changes to a person's DNA, known as genetic mutations. The first mutations described in association with<unk>  were in a gene responsible for a protein or ion channel that controls the flow of sodium ions through the cell membrane of heart muscle cells – the cardiac sodium channel. Many of the genetic mutations that have subsequently been described in association with<unk>  influence the sodium current in some way, or affect other ionic currents. A long list of factors that can generate a<unk>  ECG pattern have been described, including certain medications, electrolyte disturbances such as a decrease in the levels of potassium in the blood, and a reduction in blood supply to key areas of the heart, specifically the right ventricular outflow tract. Drugs that have been implicated include antiarrhythmic medications such as flecainide, verapamil and propranolol, antidepressants such as amitryptiline, and drugs that enhance vagal tone such as acetylcholine. The ECG pattern can also be seen following excessive use of alcohol or cocaine. Genetics<unk>  is inherited in an autosomal dominant manner, meaning that only one copy of the defective gene is needed to produce the syndrome. However, a person diagnosed with the condition may be the first in their family to have<unk>  if it has arisen as a new mutation. The gene in which mutations are most commonly found in<unk> , known as SCN5A, is responsible for the cardiac sodium channel. Mutations in SCN5A associated with<unk>  generally cause the flow of sodium ions to decrease. However, only 20% of cases of<unk>  are associated with mutations in SCN5A, as in the majority of patients with<unk>  genetic testing is unable to identify the genetic mutation responsible. Over 290 mutations in the SCN5A gene have been discovered to date, each altering sodium channel function in subtly different ways. This variation partially explains the differences in severity of the condition between different persons, ranging from a highly dangerous condition causing death at a young age to a benign condition that may not cause any problems at all. However, the genetics of<unk>  are complex, and it is likely that the condition results from the interactions of many genes. Because of these complex interactions, some members of a family who carry a particular mutation may show evidence of<unk>  while other carrying the same mutation may not, referred to as variable penetrance. Mutations in the SCN5A gene seem to have a prognostic value. Several other genes have been identified in association with<unk> . Some are responsible for other proteins that form part of the sodium channel, known as sodium channel β subunits (SCN1B, SCN2B, SCN3B) while others form different types of sodium channel (SCN10A). Some genes encode ion channels that carry calcium or potassium ions (CACNA1C, CACNB2, KCND3, KCNE3, KCNJ8), while others generate proteins that interact with ion channels. (GPD1L, PKP2, MOG1, FGF12). Another gene associated with this condition is RRAD. The genes associated with<unk>  and their description include: Type OMIM Gene Notes<unk> 1 SCN5A NaV1.5 – α subunit of the cardiac sodium channel carrying the sodium current INa.<unk> 2 GPD1L Glycerol-3-phosphate dehydrogenase like peptide – reduced GPD1-L activity leads to phosphorylation of NaV1.5 and decreased INa.<unk> 3 CACNA1C CaV1.2 – α subunit of voltage-dependent calcium channel carrying the L-type calcium current ICa(L).<unk> 4 CACNB2 CaVβ2B – β-2 subunit of the voltage-gated calcium channel carrying the L-type calcium current ICa(L).<unk> 5 SCN1B NaVβ1 – β-1 subunit of the sodium channel carrying the sodium current INa.<unk> 6 KCNE3 MiRP2 – β subunit to voltage-gated potassium channels. Modulates the transient outward potassium current Ito.<unk> 7 SCN3B NaVβ3 – β-3 subunit of the cardiac sodium channel carrying the sodium current INa.<unk> 8 KCNJ8 Kir6.1, carries the inward rectifier potassium current IKir.<unk> 9 CACNA2D1 α2δ subunit of the voltage-gated calcium channel carrying the L-type calcium current ICa(L).<unk> 10 KCND3 KV4.3, α-subunit of the transient outward potassium channel Ito.<unk> 11 RANGRF Encodes MOG1 – influences trafficking of NaV1.5.<unk> 12 SLMAP Sarcolemmal membrane–associated protein, a component of T-tubules and the sarcoplasmic reticulum – influences trafficking of NaV1.5.<unk> 13 ABCC9 SUR2A, the adenosine triphosphate (ATP)-binding cassette transporter of the IK(ATP) channel.<unk> 14 SCN2B NaVβ2 – Beta-2 subunit of the cardiac sodium channel carrying the sodium current INa.<unk> 15 PKP2 Plakophillin-2 – interacts with INa.<unk> 16 FGF12 Fibroblast growth factor homologous factor-1 – mutation decreases INa.<unk> 17 SCN10A NaV1.8 – α subunit of the neuronal sodium channel.<unk> 18 HEY2 Transcription factor identified in genome-wide association study.<unk> 19 SEMA3A Semaphorin.<unk> 20 KCNAB2 KVβ2, voltage-gated potassium channel β2 subunit - mutation increases Ito. Some mutations associated with<unk>  can also cause other heart conditions. Those who show more than one cardiac conditions at the same time caused by a single mutation are described as having an 'overlap syndrome'. An example of an overlap syndrome is<unk>  and long QT syndrome (LQT3) caused by a mutation in SCN5A that reduces the peak sodium current but simultaneously leaves a persistent current leak.<unk>  has been described as overlapping with arrhythmogenic right ventricular cardiomyopathy (ARVC) caused by a mutation in the PKP2 gene, causing a<unk>  ECG pattern but structural changes in the heart characteristic of ARVC.
Brugada syndrome
Arrhythmogenic cardiomyopathy
Pacak–Zhuang syndrome
Duchenne muscular dystrophy
Woodhouse–Sakati syndrome
Romano–Ward syndrome
Pascual-Castroviejo syndrome type 1
Catecholaminergic polymorphic ventricular tachycardia