Same Gene, Different Story (a Case Report of Congenital Long QT Syndrome Subtype 8 With a Novel Mutation)

Long QT syndrome (LQTS) 8 is a rare inherited channelopathy caused by CACNA1C gene mutations that affects calcium channels, and when combined with congenital heart defects, musculoskeletal defects, and neurodevelopmental defects, it is referred to as Timothy syndrome. A female patient, aged 17 years, presented with a witnessed episode of syncope secondary to ventricular fibrillation that was successfully cardioverted. Electrocardiogram showed sinus bradycardia 52/min, normal axis, and a QTc of 626 ms. In the hospital, she had another episode of asystole and Torsade de pointes and underwent successful cardiopulmonary resuscitation. Echocardiogram showed severely reduced left ventricular systolic function from postcardiac arrest myocardial dysfunction and no congenital heart defects. Long QT genetic test detected a missense mutation in the CACNA1C gene (NM_199460.3, variant c.2573G>A, p Arg858His, heterozygous, autosomal dominant), resulting in replacement of arginine with histidine at position 858(R858H), leading to the gain of function in the L-type calcium channel. Given the absence of congenital cardiac defects, musculoskeletal deformities, or neurodevelopmental delay a final diagnosis of LQTS subtype 8 was made. A cardioverter defibrillator was implanted. In conclusion, our case highlights the importance of genetic testing in the diagnosis of LQTS. Some CACNA1C mutations, such as R858H described here, cause LQTS without the extracardiac manifestations observed in classic Timothy syndrome and should be included in the genetic testing for LQTS. To the best of our knowledge, our case is the first one from United States with the R585H mutation. Three cases with similar mutations have been reported from Japan and one from New Zealand.