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

A teenager had dangerous heart rhythm problems caused by a rare genetic condition called Long QT syndrome. She had life-threatening episodes where her heart stopped beating properly. Genetic testing found a new mutation in a gene that affects heart rhythm. Unlike other people with mutations in the same gene, she didn't have other health problems like heart defects or developmental delays. This shows that the same gene can cause different symptoms in different people.

This case report describes a 17-year-old female with Long QT syndrome subtype 8 (LQTS8) caused by a novel CACNA1C gene mutation (R858H). The patient presented with life-threatening cardiac arrhythmias including ventricular fibrillation and Torsade de pointes, requiring cardioversion and cardiopulmonary resuscitation. Genetic testing revealed a missense mutation affecting L-type calcium channels. Notably, this patient lacked the extracardiac features typically seen in Timothy syndrome (congenital heart defects, musculoskeletal abnormalities, neurodevelopmental delays), despite having the same gene mutation.

This is reportedly the first case of this specific mutation documented in the United States, with similar cases previously reported in Japan and New Zealand.

Highlights importance of comprehensive genetic testing in LQTS diagnosis. Suggests CACNA1C mutations should be included in LQTS genetic panels even without Timothy syndrome features. Emphasizes need for immediate cardiac monitoring and intervention in suspected cases.

Single case report limits generalizability. No long-term follow-up data provided. Limited family history or segregation analysis reported. Cannot establish causality definitively from single case.

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.