All Along the Watchtower: a Case of Long QT Syndrome Misdiagnosis Secondary to Genetic Testing Misinterpretation

Abstract

Clinical genetics services continue to expand into diverse medical specialties. An ever-increasing number of non-genetics providers are independently ordering genetic tests, interpreting results, and at times, making diagnoses leading to patient care recommendations. Non-genetics healthcare providers can help increase patient access to these services, but a potential pitfall occurs when these providers either do not have adequate expertise with genetic variant interpretation or do not have access to multi-disciplinary teams including genetic counselors or clinical geneticists for advanced review. In the cardiology setting, variant misinterpretation can lead to misattribution of disease risk, unnecessary treatments or management, and potentially adverse psychosocial and financial effects. To address this, case reports and series are needed to highlight variant misinterpretation and misdiagnoses, including discussion of possible solutions and best practices for avoidance. This report details a child previously diagnosed with long QT syndrome type 4 by chromosomal microarray who was then subsequently managed for this disease by cardiac providers with insufficient expertise to critically review and question the genetic testing results. The patient was eventually referred to a pediatric electrophysiology team as part of a larger multidisciplinary cardiovascular genetics program, composed of specialist genetic counselors, cardiologists, and clinical geneticists. Advanced review and clinical evaluation raised concern about the initial genetic testing result and diagnosis. Complementary testing with a different modality to confirm or disconfirm the chromosome microarray result was performed, providing evidence that the original result reflected analytic error in the laboratory as well as interpretive error by the clinical geneticist and that the patient was misdiagnosed, and treated over the course of years, for long QT syndrome. This case shows the value of multidisciplinary teams caring for patients with inherited cardiovascular diseases.

Keywords: ANK2; Cardiovascular genetics; Chromosome microarray; Genetic counseling; Long QT syndrome; Misdiagnosis; Multidisciplinary.