In the present study, a heterozygous missense mutation (A561V) linked to LQT2, syncope and epilepsy was identified in the S5/pore region of the hERG protein.
This fact raises the possibility that R863X alteration in KCNH2-encoded potassium channel may confer susceptibility for epilepsy and cardiac LQT-2 arrhythmia.
Like noncardiac organ phenotypes observed in other LQTS-susceptibility genes such as KCNQ1/deafness and SCN5A/gastrointestinal symptoms, this novel LQT2-epilepsy association raises the possibility that LQT2-causing perturbations in the KCNH2-encoded potassium channel may confer susceptibility for recurrent seizure activity.
Altered exon copy number was detected in 3 (11.5%) patients: (1) an ex13-14del of the KCNQ1 gene in an 11-year-old boy with exercise-induced collapse (QTc 580 ms); (2) an ex6-14del of the KCNH2 gene in a 22-year-old woman misdiagnosed with epilepsy since age 9 years (QTc 560 ms) and a sibling with sudden death at age 13 years; and (3) an ex9-14dup of the KCNH2 gene in a 12 year-old boy (QTc 550 ms) following sudden nocturnal death of his 32-year-old mother.