An Update on Channelopathies

The basic science of membrane channels has set in motion striking clinical results, especially in cardiology. The clinical phenotype of cardiac channelopathies is conspicuous; sudden death or cardiac arrest may be the initial presentation. The last 2 decades have changed the face of diagnosis and treatment of inherited channelopathies for families who have a high, and often unrecognized, likelihood of sudden death.The simple paradigm of one gene, one mutation, one disease remains true in some channelopathy diseases, but as we look deeper, the relationships increase in complexity as channel biology interrelates with membrane, intercellular, and extracellular biology. No protein acts in isolation. Genetic testing ideally identifies patients at risk, offers a window into optimal therapy, and aids in identifying those patients who are not carriers and therefore assign them to a low-risk group. However, the best-case scenario is not always the clinical scenario. The task of the clinical practitioner is to digest the flood of basic science information and use it to best serve patients.As the prevalence of genetic testing has increased, the limitations become more important to the practicing physician. Testing may reveal a change in the patient’s genome from the typical sequence, but certifying a mutation as the clinical cause of a patient’s disease remains a challenge. Along with the difficult task of learning the names and nuances of the genetic products (eg, the LQT1 genotype stems from mutations in KCNQ1 , previously known as KVLQT1 , on chromosome 11p15.5, encoding Kv7.1, which conducts an IKs current), the practitioner must learn a new genetic vocabulary to convert a cardiac genetic test report into an informed clinical decision. The aim of this review is to summarize the scope of arrhythmia genetics and relate those mechanisms to clinical management strategies.When Keating et al1 made the …