A newly characterized SCN5A mutation underlying Brugada syndrome unmasked by hyperthermia.
Febrile illness has been rarely reported to modulate ST segment elevation in right precordial leads on ECG or even precipitate ventricular fibrillation in patients with Brugada syndrome. We report the case of a patient whose Brugada ECG pattern was unmasked by hyperthermia secondary to acute cholangitis. Serial ECGs showed progressive attenuation of ST segment elevation as body temperature gradually returned to normal. Structural heart disease was ruled out. Intravenous flecainide injection reproduced a less remarkable ST segment elevation. Genetic screening demonstrated a single amino acid substitution (H681P) in the SCN5A gene, thus confirming the diagnosis of Brugada syndrome. In vitro expression of this newly characterized genetic defect revealed novel biophysical abnormalities consisting of a shift in both steady-state activation and inactivation, resulting in a 60% reduction of sodium window current. Thus, SCN5A-H681P mutation induces a significant loss of transmembrane current and is clinically associated with a pathologic phenotype that is elicited by hyperthermia. Overall the observed clinical features are in agreement with previous observations and strongly suggest that fever may be an environmental modifier among Brugada syndrome patients with a detrimental (and possibly arrhythmogenic) effect on cardiac repolarization.
Cardiology Team, Department of Medicine & Geriatrics, Princess Margaret Hospital, Lai Chi Kok, Kowloon, Hong Kong, China. isaacmok@netvigator.com
Ngai-Shing
NS
Mok
Silvia G
SG
Priori
Carlo
C
Napolitano
Ngai-Yin
NY
Chan
Mohamed
M
Chahine
Ghayath
G
Baroudi
D000889:Anti-Arrhythmia Agents; D001145:Arrhythmias, Cardiac / Q000175:diagnosis* / Q000235:genetics*; D002037:Bundle-Branch Block / Q000175:diagnosis* / Q000235:genetics*; D002761:Cholangitis / Q000150:complications; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D016757:Death, Sudden, Cardiac / Q000473:pathology*; D004562:Electrocardiography; D005334:Fever / Q000209:etiology / Q000503:physiopathology*; D005424:Flecainide; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D062554:NAV1.5 Voltage-Gated Sodium Channel; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015222:Sodium Channels / Q000235:genetics* / Q000378:metabolism; D013577:Syndrome
D000889:Anti-Arrhythmia Agents; D018076:DNA, Complementary; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels; D005424:Flecainide