Author: Amy Babb, MD - Vanderbilt University Medical Center - Monroe Carell Jr. Children's Hospital at Vanderbilt
A 4-year-old child with genetically confirmed Timothy syndrome presents for syndactyly repair. Which of the following cardiac abnormalities is MOST commonly associated with Timothy syndrome?
EXPLANATION
Timothy Syndrome (TS), also called long QT syndrome (LQTS) type 8, is a rare autosomal dominant channelopathy caused by gain-of-function variants in the CACNAIC gene.1,2 This gene encodes the cardiac L-type calcium channel and leads to markedly prolonged ventricular repolarization and high risk of malignant arrhythmias.1,2 The full syndrome manifests with QTc prolongation, syndactyly, neurodevelopmental disorders, and unique facial features (flat nasal bridge, low-set ears, a small upper jaw, and thin upper lip).1 TS has an especially high propensity for ventricular tachycardia, torsades de pointes, and sudden cardiac death – often beginning in early childhood.1
Anesthesia management for individuals with TS should emphasize preoperative risk stratification and optimization by reviewing recent ECG/QTc intervals, ensuring continuation of beta-blockers, correcting electrolyte abnormalities (ie, potassium, magnesium, calcium), avoiding excessive NPO time, and providing a calm preoperative environment. 2,3
Perioperative management must include access to emergency medications, like magnesium as well as defibrillator/pacing capabilities.2,3 Many medications given during anesthesia/surgery can influence the QTc interval.2,3 There is no one single best anesthetic agent for patients with TS; the practical strategy includes avoiding stacking QT-prolonging medications, using the lowest effective doses, and preventing sympathetic spikes from pain or laryngoscopy.2,3
Sedation and anxiolysis to blunt catecholamine-mediated triggers can be beneficial with agents like midazolam, which have minimal effect on the QTc interval.3 During induction and maintenance of anesthesia, avoidance or careful titration of medications known to prolong QTc are critical.2,3 A total intravenous anesthetic technique is often used when weighing the risk of QT prolongation with volatile agents.3
Postoperative care must include continuous ECG monitoring and ensuring adequate analgesia.2,3
Postoperative nausea prevention deserves special consideration when managing a patient with Timothy syndrome since common anti-emetics, like ondansetron, are known to lengthen the QTc interval.2 Dexamethasone, aprepitant, and scopolamine patches have minimal effect on the QTc interval and are good alternatives.3
The hallmark of Timothy syndrome is a markedly prolonged QTc interval, and thus the correct answer. Congenital complete heart block is often associated with anti-Ro/SSA and anti-La/SSB maternal antibodies and supravalvular aortic stenosis is commonly associated with Williams syndrome.
EXPLANATION
1. Dufendach KA, Timothy K, Ackerman MJ, et al. Clinical Outcomes and Modes of Death in Timothy Syndrome: A Multicenter International Study of a Rare Disorder. JACC Clin Electrophysiol. 2018;4(4):459-466. doi:10.1016/j.jacep.2017.08.007
2. Nathan AT, Antzelevitch C, Montenegro LM, Vetter VL. Case scenario: anesthesia-related cardiac arrest in a child with Timothy syndrome. Anesthesiology. 2012;117(5):1117-1126. doi:10.1097/ALN.0b013e31826e73b1
3. Niimi N, Yuki K, Zaleski K. Long QT Syndrome and Perioperative Torsades de Pointes: What the Anesthesiologist Should Know. J Cardiothorac Vasc Anesth. 2022;36(1):286-302. doi:10.1053/j.jvca.2020.12.011