Cardiology/original researchMisdiagnosis of Long QT Syndrome as Epilepsy at First Presentation
Introduction
It has been 25 years since the first case report of long QT syndrome being misdiagnosed as epilepsy was published.1 Several other cases have since appeared in the literature.2, 3, 4 We recently reported the history of a 12-year-old boy diagnosed with and treated for epilepsy who was subsequently a victim of sudden death. Although his death was initially ascribed to sudden unexplained death in epilepsy, posthumous genetic screening identified long QT syndrome type 1.5
The natural history of long QT syndrome suggests mortality greater than 20% in the year after the first syncopal event, with nearly 50% mortality at 5 years.6 Appropriate intervention can significantly reduce mortality and morbidity, making prompt diagnosis essential.7, 8, 9, 10
Concerned by the ongoing delayed recognition of a condition with preventable mortality, we aimed to establish the frequency of this problem in a series of patients with genetically confirmed long QT syndrome. We also explored the factors contributing to, and the consequences of, diagnostic delay of long QT syndrome.
Section snippets
Materials and Methods
Between 2000 and 2005, 84 families underwent molecular diagnostic screening through the Cardiac Inherited Disease Registry in New Zealand. A team of physicians interested in inherited causes of arrhythmia and sudden death has formed across the country, with members in all the major centers. These physicians are involved in the majority of cases of long QT syndrome nationwide and arrange genetic testing, although they would not see all case patients. Physicians in the Cardiac Inherited Disease
Results
Thirty-one gene-positive probands were identified. The presentation resulting in eventual diagnosis of long QT syndrome was syncope in 20 (64.5%), resuscitated cardiac death requiring defibrillation in 6 (19.5%), incidental ECG abnormality in 3 (10%), palpitations in 1 (3%), and prenatal bradycardia in 1 (3%). The molecular mutations in these patients were consistent with LQT1 in 18 (58%), LQT2 in 10 (32%), and LQT3 in 3 (10%). Seventy-one percent of probands were female patients. The median
Limitations
This study was subject to all the usual pitfalls of retrospective review. Data recorded at the time of presentation were not collected for the purposes of later study. The information was collected by the first author, who was not blinded to the final diagnosis of long QT syndrome in these patients. Patient numbers are small, not all patients in the registry consented for review of medical records, and the study was restricted to those who had positive genotype testing results. Previous
Discussion
The first description of a long QT syndrome in 1957 was of a recessive form associated with deafness,15 followed in the 1960s by reports of a syndrome with autosomal dominant inheritance.16, 17 The first study using linkage analysis to establish an underlying genetic basis was published in 1991.18 To date, we know of 11 genes associated with long QT syndrome. Within these genes, there are more than 600 mutations described thus far, highlighting the significant genetic heterogeneity of the
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Supervising editor: Keith A. Marill, MD
Author contributions: All authors participated in the concept, design, analysis, writing, and revision of the article. JS takes responsibility for the paper as a whole.
Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article, that might create any potential conflict of interest. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement. The Cardiac Inherited Disease Group is supported by Cure Kids, the Green Lane Research and Education Fund and the Lion Foundation. Dr. MacCormick was supported by a research fellowship grant from the Southern Trust.
Publication date: Available online March 12, 2009.
Reprints not available from the authors.