A 14-year-old boy had a witnessed syncopal episode while swimming. His father died suddenly at age 30 during exercise. Resting ECG shows a QTc of 500 ms with broad-based T waves. Genetic testing would most likely reveal a mutation affecting which current?
- A Loss-of-function mutation reducing IKr
- B Gain-of-function mutation increasing IKs
- C Loss-of-function mutation reducing IKs ✓
- D Gain-of-function mutation increasing late INa
Correct answer: C. Loss-of-function mutation reducing IKs
Explanation
Swimming and exercise-triggered syncope with broad-based T waves defines LQT1, caused by loss-of-function mutations in KCNQ1 that reduce the slowly activating delayed rectifier current IKs. LQT2 reduces IKr and is triggered by auditory stimuli and postpartum state with notched T waves. Gain-of-function mutations produce short QT rather than long QT syndromes. First-line therapy in LQT1 is a beta blocker, with left cardiac sympathetic denervation or ICD in high-risk cases.
Reference: Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 12th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.