New onset seizures in a patient with Long QT Syndrome (LQTS2) and a pathogenic carboxyl-terminus frameshift variant of the KCNH2 gene

Abstract

In patients with Long QT Syndrome (LQTS), mutations in the potassium channel KCNH2 gene increase seizure susceptibility with missense mutations involving the pore region of the gene acting as a positive predictor of seizures. Seizures are less commonly reported in patients with carboxyl (C′)-terminus mutations. This case report describes a young man who presented with syncope followed by a first seizure and was found to have LQTS caused by a pathogenic carboxyl-terminus deletion/frameshifting mutation of the KCNH2 gene. He later had a second seizure after anti-seizure medication taper. This mutation has not previously been reported associated with seizures. Our case suggests that, in patients with this type of C′-terminus mutation and a first seizure or syncope, there is a susceptibility to epilepsy. As inherited congenital heart disease may be a risk factor for sudden unexpected death in epilepsy (SUDEP), attention to all specific genetic markers in a young patient with QT prolongation and a first seizure could guide the use of anti-seizure medication to reduce the risk of SUDEP.