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A 13-year-old girl with Jervell and Lange-Nielsen syndrome associated congenital long QT syndrome (LQTS) and central deafness was admitted for generalized seizures. LQTS had been diagnosed after birth and confirmed at genetic testing. β-blocker treatment was immediately started. Despite this, since the age of 12 months, recurrent cerebral seizures occurred leading to the diagnosis of epilepsy. Anti-convulsive therapy was initiated but without success. At the last admission, nadolol dosage seemed infratherapeutic. Considering malignant ventricular arrhythmias as the cause of seizures, the β-blocker dosage was adjusted to weight and levels of magnesium and potassium optimized. Furthermore, the patient received an implantable Medtronic Reveal LINQ Recorder®. Since then, the adolescent has been asymptomatic with no arrhythmia documented. LQTS is due to one or more mutations of genes coding for ion channels. It may induce malignant ventricular arrhythmias and is a major cause of sudden cardiac death in children. Generalized cerebral seizures are extra-cardiac manifestations caused by decreased cerebral perfusion during ventricular arrhythmia. They are commonly misinterpreted as manifestations of epilepsy. For any patient with known or unknown LQTS who presents seizures with resistance to anti-convulsive therapy, a cardiac electrophysiological investigation should be performed promptly to ensure etiological diagnosis and optimize treatment.

Rapid Whole Genome Sequencing (rWGS) represents a valuable exploration in critically ill pediatric patients. Early diagnosis allows care to be adjusted. We evaluated the feasibility, turnaround time (TAT), yield, and utility of rWGS in Belgium. Twenty-one unrelated critically ill patients were recruited from the neonatal intensive care units, the pediatric intensive care unit, and the neuropediatric unit, and offered rWGS as a first tier test. Libraries were prepared in the laboratory of human genetics of the University of Liège using Illumina DNA PCR-free protocol. Sequencing was performed on a NovaSeq 6000 in trio for 19 and in duo for two probands. The TAT was calculated from the sample reception to the validation of results. Clinical utility data were provided by treating physicians. A definite diagnosis was reached in twelve (57.5%) patients in 39.80 h on average (range: 37.05–43.7). An unsuspected diagnosis was identified in seven patients. rWGS guided care adjustments in diagnosed patients, including a gene therapy, an off-label drug trial and two condition-specific treatments. We successfully implemented the fastest rWGS platform in Europe and obtained one of the highest rWGS yields. This study establishes the path for a nationwide semi-centered rWGS network in Belgium.