Abstracts

Rationale: Many idiopathic epilepsies have been shown to be caused by channelopathies. It has recently been suggested that the same mutation may cause both the familial long QT syndrome (LQTS) and epilepsy. This may be important since a patient with epilepsy and a concurrent cardiac ion channel mutation may be at risk for serious cardiac arrhythmias and sudden unexpected death in epilepsy (SUDEP), especially when exposed to drugs that also interfere with cardiac ion channels. Methods: The patient was a previously healthy female with epilepsy debut at the age of 17. She was diagnosed with simple, complex partial and secondary generalized seizures. The seizures started with a feeling of déjà vu. She also had a few myoclonic seizures. Her EEG showed frequent bursts of bilateral synchronous epileptogenic activity lasting up to 2-3 seconds. Cerebral MRI was normal. When she died in SUDEP at the age of 25 she was treated with lamotrigine (LTG) 100 mg/day in monotherapy. DNA sequencing of the translated exons with flanking intron sequences of the LQTS-associated genes KCNQ1, HERG, SCN5A, minK and MiRP1 was performed to study whether the patient actually had a channelopathy. Results: The molecular genetic analyses revealed that the patient was heterozygous for the novel missense mutation R523C in exon 12 of the SCN5A gene coding for the cardiac sodium channel, voltage gated, type V, alpha subunit. This mutation was not identified in 315 unrelated Norwegian subjects referred for genetic testing with respect to LQTS, and was predicted to be pathogenic by the use of the prediction program PolyPhen. Conclusions: This new SCN5A mutation may help to explain the sudden death of our patient either by causing LQTS or by causing a predisposition to drug-induced cardiac arrhythmias. Our patient was treated with LTG in monotherapy; a drug which interfere with both sodium and potassium channel functions. We have so far no evidence that the same mutations was also responsible for the epilepsy in this patient, but this may be a possibility as SCN5A is also expressed in limbic regions.