KCNH2 variants in a family with epilepsy and long QT syndrome: A case report and literature review.

OBJECTIVE: Genes associated with Long QT syndromes (LQTS), such as KCNQ1, KCNH2, and SCN5A, are common causes of epilepsy. The Arg 744* variant of KCNH2 has been previously reported in people with epilepsy or LQTS, but none of these patients were reported to simultaneously suffer from epilepsy and LQTS. Herein, we report the case of a family with epilepsy and cardiac disorders.

METHOD: The proband, a 25-year-old woman, with a family history of epilepsy and LQTS was followed at West China Hospital. The proband experienced her first seizure at the age of seven. Video electroencephalograms (vEEGs) showed epileptic discharges. Her 24-h dynamic electrocardiograms 2 (ECGs) showed QTc prolongation. The proband's mother, who is 50 years old, had her first generalized tonic-clonic seizure (GTCS) at the age of 18 years old. After she gave birth at the age of 25, the frequency of seizures increased, so antiepileptic therapy was initiated. When she was 28 years old, she complained of palpitations and syncope for the first time, and QTc prolongation was detected on her 24-h dynamic ECGs. The proband's grandmother also had complaints of palpitations and syncope at the age of 73. Her 24-h dynamic ECGs indicated supraventricular arrhythmia, with the lowest heart rate being 41 bpm, so she agreed to a pacemaker. Considering the young patient's family history, blood samples of the patient and her parents were collected for genetic analysis.

RESULTS: A heterozygous variant of KCNH2 [c.2230 (exon9) C>T, p. Arg744Ter, 416, NM_000238, rs189014161] was found in the proband and her mother. According to the guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, we classified the KCNH2 variant as pathogenic.

SIGNIFICANCE: This study expands the clinical phenotype of the Arg 744* KCNH2 pathogenic variant. In the context of channelopathies, because of the genetic susceptibility of the brain and the heart, the risk of comorbidity should be considered. This also indicates the importance of precise antiepileptic drug (AED) management and regular ECG monitoring for patients with channelopathies.