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Amy Daly was born on August 22, 1982 in Los Angeles, California, USA. She is an actress and writer, known for The Forbidden Dimensions (2013).
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Home InVitae Department of Genetics Amy Daly
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
Aim:
Our aim was to examine the diagnostic yield of genetic testing in 855 consecutive unrelated cases referred for Long QT syndrome (LQTS).
Results:
Eight hundred fifty five consecutive patients with a mean age at testing of 27.5±18.6 years, were referred for LQTS genetic testing and had accompanying clinical information. KCNQ1, KCNH2, SCN5A, ANK2, KCNE1, KCNE2, CACNA1C, KCNJ2, CAV3, and SCN4B were analyzed using Next-Generation sequencing in all patients, and 395 patients were also tested for an additional two genes, AKAP9 and SNTA1. We retrospectively analyzed the diagnostic yield of this genetic test and factors that predicted the likelihood of a disease causing mutation using ANOVA, χ2, t-test, and receiver operator curves. At least one mutation was identified in 30.3% of the patients (n=259), and 18 patients (2.1%) had two mutations. Patients with two mutations had a longer QTc interval (p<0.01) than patients with one mutation. A longer QTc duration and family history of LQTS were each associated with a higher yield of positive results on genetic testing (p<0.01 for each). Using a QTc cutoff of 476 msec or greater, the genetic testing had a sensitivity of 72% and a specificity of 49%. Mutations within the transmembrane domain of KCNQ1 were associated with a greater risk of cardiac arrest and syncope relative to mutations in other domains of the gene. Mutations in SCN5A were associated with a higher frequency of cardiac arrest (52.6%).
Conclusion:
Sequencing-based genetic testing has a sensitivity of 72% and has clinical utility.
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited form of cardiomyopathy with low penetrance and variable expressivity. Dominant mutations and rare polymorphisms in desmosome genes are frequently identified. We reasoned that individuals with earlier onset disease would have more frequent desmosome gene mutations and rare polymorphisms. Three groups were compared: Young with symptoms attributable to ARVD/C or a diagnosis of ARVD/C at age of 21 years or earlier, Middle with first symptoms or diagnosis age of 22-49 years, and Late with first symptoms or diagnosis at age of 50 or more years. deoxyribonucleic acid (DNA) sequence analysis was performed on five cardiac desmosome genes, and the presence of mutations and rare missense polymorphisms was compared among the three groups. In the entire Young cohort, 20 (67%) had one or more cardiac desmosome gene mutations. The prevalence of cardiac desmosome gene mutations was similar in the Middle (48%) and Late (53%) cohorts (P = 0.23). Similar numbers of individuals in each cohort had more than one desmosome gene mutation, although the numbers are too small for statistical comparisons. The prevalence of certain rare missense DNA variants was not different among the cohorts (P = 0.71), yet these rare missense alleles were more prevalent in the overall study cohort of 112 ARVD/C participants compared to 100 race-matched controls (P = 0.027). The presence of these variants did not associate with the age of onset of ARVD/C or ventricular tachycardia. These findings highlight the complex interplay of environmental and genetic factors contributing to this condition.
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is characterized by frequent life-threatening ventricular arrhythmias, diagnosed on average in the teens to mid-50s and commonly treated by implantable cardioverter defibrillators (ICDs). As younger age and high frequency of ICD discharges are risk factors for difficulties in psychosocial adjustment, we developed a study to assess psychosocial adjustment among patients with ARVD/C and to determine risk factors for poor adjustment in this high-risk population.
Eighty-six adults enrolled in the Johns Hopkins ARVD Registry (38 male; mean age, 45.4±12.9 years), with an ICD in place for a median 3.2 years (range, 0.2 to 20.1 years), completed a set of questionnaires measuring ICD-specific anxiety (Florida Shock Anxiety Scale), device acceptance (Florida Patient Acceptance Survey), anxiety and depression (Hospital Anxiety and Depression Scale), and functional capacity (Duke Activity Status Index). Although overall device acceptance (Florida Patient Acceptance Survey mean, 76.7±15.3) was normative, patients with ARVD/C had substantially elevated body image concerns (Florida Patient Acceptance Survey subscale mean, 17.9±23.5) and device-related distress (subscale mean, 26.5±19.2), particularly among younger patients (P<0.01). Patients with ARVD/C had elevated ICD-specific (Florida Shock Anxiety Scale mean, 22.9±7.8) and general clinical anxiety (Hospital Anxiety and Depression Scale anxiety subscale mean, 6.2±3.9). Device-specific anxiety (Florida Shock Anxiety Scale) was predicted by younger age (P<0.0001), poorer functional capacity (P=0.016), having an ICD shock (P=0.003), and shorter time since ICD implant (P=0.007). Participants with poor device adjustment had an increased likelihood of clinically significant anxiety (P=0.006) and depression (P=0.008).
Patients with ARVD/C are at elevated risk for anxiety, and young patients face challenges with device acceptance. Risk factors for poor device adjustment may be used clinically to identify patients at high-risk of psychological distress.
Aim:
Our aim was to examine the diagnostic yield of genetic testing in 855 consecutive unrelated cases referred for Long QT syndrome (LQTS).
Results:
Eight hundred fifty five consecutive patients with a mean age at testing of 27.5±18.6 years, were referred for LQTS genetic testing and had accompanying clinical information. KCNQ1, KCNH2, SCN5A, A...
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is characterized by frequent life-threatening ventricular arrhythmias, diagnosed on average in the teens to mid-50s and commonly treated by implantable cardioverter defibrillators (ICDs). As younger age and high frequency of ICD discharges are risk factors for difficulties in psycho...
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited form of cardiomyopathy with low penetrance and variable expressivity. Dominant mutations and rare polymorphisms in desmosome genes are frequently identified. We reasoned that individuals with earlier onset disease would have more frequent desmosome gene mutations and...
Introduction:
Despite the use of standardized definitions, widely varying prevalence estimates of electrocardiographic (ECG) features related to arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) have been reported in different cohorts. This study was aimed at examining the variability in the ECG interpretation resulting from the s...
We are grateful for the 2 thoughtful letters concerning our recent article1 on the ECG features of arrhythmogenic right ventricular dysfunction (ARVD). Because ECGs are widely available and inexpensive, it important for those interested in this field to fully explore the diagnostic and prognostic potential of 12-lead ECGs. There were 3 main issues...
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited disorder typically caused by mutations in components of the cardiac desmosome. The prevalence and significance of desmosome mutations among patients with ARVD/C in North America have not been described previously. We report comprehensive desmosome genetic analysis fo...
This study sought to investigate the prevalence and mechanisms underlying right ventricular (RV) dyssynchrony in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) using tissue Doppler echocardiography (TDE).
An ARVD/C is characterized by fibrofatty replacement of RV myocardium and RV dilation. These pathologic changes may result in...
The purpose of this study was to reevaluate the ECG features of arrhythmogenic right ventricular dysplasia (ARVD). The second obj
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