Abstract
BackgroundNumerous structurally unrelated drugs, including antipsychotics, can prolong QT interval and trigger the acquired long QT syndrome (aLQTS). All of them are thought to act at the level of KCNH2, a subunit of the potassium channel. Although the QT-prolonging drugs are proscribed in the subjects with aLQTS, the individual response to diverse QT-prolonging drugs may vary substantially.Case presentationWe report here a case of aLQTS in response to small doses of risperidone that was confirmed at three independent drug challenges in the absence of other QT-prolonging drugs. On the other hand, the patient did not respond with QT prolongation to some other antipsychotics. In particular, the administration of clozapine, known to be associated with higher QT-prolongation risk than risperidone, had no effect on QT-length. A detailed genetic analysis revealed no mutations or polymorphisms in KCNH2, KCNE1, KCNE2, SCN5A and KCNQ1 genes.ConclusionsOur observation suggests that some patients may display a selective aLQTS to a single antipsychotic, without a potassium channel-related genetic substrate. Contrasting with the idea of a common target of the aLQTS-triggerring drugs, our data suggests existence of an alternative target protein, which unlike the KCNH2 would be drug-selective.
Highlights
Numerous structurally unrelated drugs, including antipsychotics, can prolong QT interval and trigger the acquired long QT syndrome
Our observation suggests that some patients may display a selective acquired long QT syndrome (aLQTS) to a single antipsychotic, without a potassium channel-related genetic substrate
The aLQTStriggering drugs are supposed to act at the subunit of the potassium channel, the KCNH2, which produces the delayed rectifier K(+) current (I(Kr)) [1]
Summary
The QT prolongation in our patient fulfills the criteria for aLQTS. because of its striking drug-selectivity, we use the term “selective acquired long QT syndrome” (saLQTS). Sequencing of some other genes implicated in the pathogenesis of LQTS did not reveal any significant mutation or polymorphism in our patient, and exact molecular mechanism of the reported saLQTS remains unknown. It cannot be formally excluded that further expanding of genetic screening on all of the genes implicated in the LQTS could lead to the identification of causative mutations This seems rather unlikely, since the mutations in the five most important genes that we have already sequenced (KCNH2, KCNQ1, KCNE1, KCNE2 and SCN5A) are Consent Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Author details 1Division of General Psychiatry, University Hospitals of Geneva and Faculty of Medicine of the University of Geneva, 1202 Geneva, Switzerland. Author details 1Division of General Psychiatry, University Hospitals of Geneva and Faculty of Medicine of the University of Geneva, 1202 Geneva, Switzerland. 2Division of Old Age Psychiatry, Hospices-CHUV, 1008 Prilly, Switzerland. 3Laboratoire de Génétique Moléculaire, Service de Génétique Médicale, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
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