Neurological Anomalies Observed in Infant LQTS Patients May Be Linked to Severe Cardiac Phenotypes

Neurological disorders in perinatal LQTS patients may be caused by neurological phenotypes associated with severe cardiac phenotypes.

A high number of neurodevelopmental anomalies were found in infant patients diagnosed with long QT syndrome (LQTS). The mutations were discovered in loci linked to LQTS with a severe cardiac phenotype, according to research published in JACC: Clinical Electrophysiology.

Epilepsy and/or developmental disorders have been previously observed in perinatal LQTS patients who survived life-threatening ventricular arrhythmias. Researchers predicted that perinatal LQTS patients—the most severe LQTS phenotype—would have higher incidences of neurological manifestations. To test this hypothesis, they examined clinical and neurological findings of 21 infant patients with LQTS, with or without perinatal arrhythmias, diagnosed before 1 year of age (6 of whom were diagnosed with perinatal LQTS and 3 previously identified with neurological seizures).

Of the 6 perinatal LQTS patients, 5 (83%) were diagnosed with epilepsy and 4 (67%) were diagnosed with developmental disorders. None of the non-perinatal LQTS patients were diagnosed with either disorder. The total development quotient, calculated with the Kinder Infant Development Scale, was 17 to 72 (median 67) in the 5 epileptic perinatal LQTS cases.

Including the 3 previously reported cases, 8 perinatal LQTS patients had neurological disorders. Among these patients, epileptic seizures occurred between 2 days and 2.5 years old, and 5 had developmental disorders. The mutations of these 8 patients were found in the transmembrane loop of KCNH2, and D3/S4-S5 linker, D4/S4, or the D4/S6 segment of SCN5A.

During the follow-up, syncope or life-threatening arrhythmias occurred in 5 (83%) perinatal LQTS patients, and 1 (7%) non-perinatal LQTS patient.

“Although we could not completely deny the possibility that the neurological disorders were the result of a brain perfusion injury,” the authors wrote, “our findings suggested that the channel dysfunction leading to a most severe cardiac phenotype may also confer susceptibility to a neurological phenotype.”

The authors noted that additional studies should investigate causes of neurodevelopmental anomalies in perinatal LQTS. “Current therapies have resulted in relatively favorable life prognoses in peri-natal LQTS,” they authors stated. “Based on our findings that they have a high comorbidity of neurological disorders, the improvement of their developmental prognoses should be considered as the next step of the medical treatment.”


Miyazaki A, Sakaguchi H, Aiba T, et al. Comorbid epilepsy and developmental disorders in congenial long QT syndrome with life-threatening perinatal arrhythmias. JACC Clin Electrophysiol. 2016. doi:10.1016/j.jacep.2015.10.010.