Introduction: The diagnosis of Brugada syndrome requires the recording of a Brugada type-1 ECG, either spontaneously or after provocation with sodium-channel blockers such as ajmaline. Additionally, genetic testing and family screening is recommended in all patients. Most mutations are found in the SCN5A gene, encoding the voltage-dependent cardiac sodium channel NaV1.5. However, certain mutations in SCN5A are associated with other diseases, such as long QT syndrome, cardiac conduction disease and sick sinus syndrome. The pathophysiology of these diseases and the association between genotype and phenotype remain poorly understood. Here, we present the case of a teenage boy showing Brugada-type-1 ECG as well as sinus arrest during ajmaline challenge.

Methods: Clinical work-up included the patient’s history as well as family history, ECG recordings, echocardiography and ajmaline challenge. Genetic testing was performed and the detected SCN5A mutation was analyzed in whole cell patch clamp experiments with transiently transfected HEK-293T cells.

Results: A 12 year-old boy was referred to our clinic for ajmaline challenge. The index patient, his older brother, had survived sudden cardiac arrest at the age of 11 months. His grandfather had died suddenly at the age of 36. His mother was asymptomatic, but was diagnosed with Brugada syndrome following ajmaline challenge. The boy had already received an ICD at the age of 3 ½ years due to the suspected familial channelopathy and recurrent syncopes. However, ajmaline challenge was not performed at that time, due to the young age and the family’s wish. In both boys and the mother, a variant of unknown significance (VUS) was discovered in SCN5A (GGCàAGC; p.Gly1712Ser). Matching the diagnosis of familial Brugada syndrome, patch clamp functional analysis revealed a loss-of-function mutation, causing reduced peak currents, delayed recovery from inactivation and enhanced slow activation of the channel. At presentation in our clinic, the boy had a normal baseline ECG, and normal physical examination as well as echocardiography. During ajmaline challenge, administration of 30 mg (body weight 60 kg) caused intermittent sinus arrest with ventricular back-up pacing at 40 bpm. Simultaneously, a Brugada type-1 ECG was unmasked, confirming the diagnosis of Brugada syndrome.

Conclusion: We present the rare case of a boy diagnosed with familial Brugada syndrome, bearing a loss-of-function mutation in SCN5A, who developed sinus arrest under administration of ajmaline. Such findings may have implications for therapy and illustrate how elusive the association between genotype and phenotype is. A thorough individual examination is mandatory for each patient to enable individual risk stratification and therapy.