The term Sudden Unexpected (Unexplained) Death in Epilepsy (SUDEP) refers to the unexpected death of a person with epilepsy, who was otherwise healthy, and for whom no other cause of death can be found. Between 500 and 1,000 people with epilepsy die of SUDEP in the UK each year. It is thought that these deaths are in most cases related to a severe convulsive seizure affecting vital functions such as breathing or heart rhythm. Despite ongoing research, risk factors for SUDEP are only partly understood. This is particularly distressing for the families of those affected. One of the hypotheses put forward in the last few years is that a sub-group of those who die unexpectedly have a genetic predisposition to both sudden death and epilepsy.

Scientists at Baylor College of Medicine, in Texas, US, have made a very recent breakthrough in SUDEP research, by identifying a gene mutation that links seizures with predisposition to sudden cardiac death. The gene in question is known as KCNQ1 and it encodes a potassium ion channel called KvLQT1.

Until now, KvLQT1 was thought only to be found in heart muscle cells, and defects in this channel (caused by a mutation in the KCNQ1 gene) have long been known to be a cause of long QT syndrome. Long QT syndrome is a condition in which the heart muscle takes longer than normal to recover from each contraction, leading to abnormal heart rhythms (arrhythmias). If not treated, severe arrhythmias can potentially lead to sudden death, as the heart fails to provide enough blood to meet the body's needs.

The researchers in Texas discovered that KvLQT1 channels are not, in fact, only found in the heart, but also in brain cells. Moreover, they showed in animal models that the same mutation in KCNQ1 that can lead to long QT syndrome also causes seizures.

These findings are interesting, as they provide support for this hypothesis that ion channel genetic mutations can cause both epilepsy and sudden death. According to the investigators on this project, screening for this mutation would be a relatively simple process. The person would first undergo a routine echocardiogram, looking at their heart's activity; and if an arrhythmia was detected / suspected, an analysis of their DNA would be performed, looking for mutated KCNQ1. Those people with positive results could be given anti-arrhythmic medication in addition to their seizure medication, potentially avoiding the fatal effect of the arrhythmia.

It is still early days however and some caution is needed. Firstly, this particular gene, if found in human idiopathic epilepsy, may only be relevant in a small population. Secondly, genes for other ion channels could also play a role in SUDEP, and so screening for one gene is unlikely to provide a definitive answer. In addition, when epilepsy is 'acquired' (for example due to severe head injury or infection etc), it is very unlikely to have a genetic basis, so here genetic screening will not be of use.

Yet despite these reservations, this work takes us a step forward in the understanding of possible mechanisms underlying SUDEP. The scientists in Texas are now screening a population of people with idiopathic epilepsy for the KCNQ1 mutation. We look forward to the results of this study.

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