P4797Genetic testing in 101 consecutive lone atrial fibrillation patients is able to identify a subgroup with increased severity

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
G D'Arezzo Pessente ◽  
F D Darrieux ◽  
L S Sacilotto ◽  
N O Olivetti ◽  
F W Wulkan ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Genetic Testing ◽  
Family History ◽  
Sudden Death ◽  
Genetic Variants ◽  
Family Members ◽  
Young Patients ◽  
National Council ◽  
Severe Phenotype ◽  
History Of

Abstract Introduction Atrial fibrillation (AF) is the most common arrhythmia and the cause of 15% of all strokes and up to 6% of medical admissions. It is estimated that currently about 2.0 million Brazilians, and 30 million individuals worldwide, are affected by the disease. It is a complex and multifactorial disease, and the mechanisms are still not well understood. Between 10–20% of AF patients do not have any known predisposing factors, a condition once called “lone AF”. The role of genetic testing still remains controversial in this clinical scenario. Purpose The aim of this study was to identify the occurrence of pathogenic genetic variants in patients with atrial fibrillation without known risk factors. Methods In a tertiary hospital, 101 young patients with apparent “lone AF” were screened with genetic testing by NGS using a custom genetic panel with 159 channelopathy and cardiomyopathy related genes. Variants found were classified according to the American College of Genetic and Genomic (ACMG) criteria. Subjects were evaluated with clinical and familial history, electrocardiogram, 24 hours Holter monitoring, echocardiogram, cardiac MRI and treatment response. Multivariate analyses were performed by logistic linear regression model. Results During an inclusion period of 4 years, 101 consecutive patients, with mean age of 38.6 years old, were classified as “lone AF” (78% male); 76% presented paroxysmal AF and 24% persistent/permanent AF. Family history of early sudden death (bellow 60 years old) was reported in 37% of cases (78% below 50 years old); 10% had family members with pacemakers; and 44% reported having family members with early AF onset. Genetic testing demonstrated that 14/101 (13.8%) of patients presented genetic variants classified as pathogenic or likely pathogenic (P/LP) according to ACMG criteria. The genes most frequently affected were LMNA (3/101), ANK2 (3/101) and truncating variants in TTN (3/101). Two variables were significantly associated with harboring a pathogenic mutation: family history of sudden death (OR: 5.58; 1,19–26,12 CI; p=0.029) and pacemaker reported in the family history (OR: 6.83; 1.11–42.04 CI; p=0.038). Conclusion Our data showed that approximately 15% of “lone AF” patients are carriers of known pathogenic mutations in genes associated with inherithed cardiomyopathy. In addition, we show that being a carrier is potentially associated with a more severe phenotype. These findings suggest that genetic testing in “lone AF” patients may be able to identify a subgroup with a more severe phenotype are for whom a different management strategy might be indicated. Acknowledgement/Funding National Council for Scientific and Technological Development (CNPq)

P6580Prevalence and clinical significance of latent Brugada syndrome in juvenile lone atrial fibrillation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Fathy ◽  
L Gaido ◽  
S Quaranta ◽  
M Anselmino ◽  
C Giustetto ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Family History ◽  
Clinical Characteristics ◽  
Young Patients ◽  
P Value ◽  
Lone Atrial Fibrillation ◽  
History Of ◽  
Group 2 ◽  
Group 1

Abstract Introduction Brugada syndrome (BrS) cause about 20% of sudden cardiac death (SCD) in young healthy adults. Nearly 20% of Brugada patients develop supraventricular arrhythmias, mostly atrial fibrillation (AF). But whether lone AF may be the first clinical manifestation in young patients with latent BrS remains unclear. Purpose To estimate the prevalence and clinical significance of latent Brugada ECG pattern in young population (age ≤45 years) with lone AF. Methods A total of 78 patients with lone atrial fibrillation (mean age 35±7) were selected from 111 young patients with juvenile atrial fibrillation (age ≤45 years) between January 2015 and November 2017. All patients were clinically evaluated. Moreover 12 lead-24H Holter ECG and pharmacological class 1C antiarrhythmic drug (AAD) test were done for high suspicious cases of Brugada ECG. The diagnosis of Brugada ECG pattern was established according to the second consensus report criteria 2005 and since 2013, according to HRS/EHRA/APHRS expert consensus statement. Results According to the study protocol, we considered two groups of patients, group 1: 13 patients (16.7%; mean age 37±8) were diagnosed with type 1 Brugada ECG pattern (3 during class 1C AADs therapy and 10 induced by class 1C AAD test), group 2: 65 patients (83%; mean age 35±7) diagnosed as lone AF without type 1 Brugada ECG. The clinical characteristics of the two groups are described in table 1. Regarding to group 1, two patients had positive electrophysiological study with subsequent ICD implantation and genetic test for SCN5A mutation was positive in 3 patients. Table 1. G1, G2 clinical characteristics Patients characteristics Group 1 (n=13) Group 2 (n=65) P value Mean age (years) 37±8 35±7 0.42 Gender (Male %) 7 (54%) 54 (83%) 0.02 Family history of BrS 2 (15%) 0 (0%) 0.03 Family history of SCD 1 (8%) 1 (1.5%) 0.20 Syncope 4 (31%) 5 (8%) 0.02 Sick Sinus Syndrome 1 (8%) 7 (11%) 0.70 Paroxysmal AF 12 (92%) 54 (83%) 0.40 Suspected basal ECG for BrS 13 (100%) 28 (43%) <0.01 Statistical test is considered significant when p value <0.05. Conclusions Up to our knowledge this study is the first one that estimate the prevalence of latent BrS in juvenile lone AF patients. Young patients with lone AF had a high prevalence of latent BrS. Syncope, family history of SCD and family history of BrS are significant indicators of the presence of latent BrS in young patients with lone atrial fibrillation.

scholarly journals Sudden death in a young patient with atrial fibrillation

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
María Tamargo ◽  
María Ángeles Espinosa ◽  
Víctor Gómez-Carrillo ◽  
Miriam Juárez ◽  
Francisco Fernández-Avilés ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Cardiac Arrest ◽  
Genetic Testing ◽  
Sudden Death ◽  
Clinical Data ◽  
Molecular Mechanisms ◽  
Young Patients ◽  
Structural Heart Disease ◽  
Polymorphic Ventricular Tachycardia ◽  
Qt Syndrome

Sudden cardiac death (SCD) in young patients without structural heart disease is frequently due to inherited channelopathies such as long QT syndrome (LQTS), Brugada syndrome or Catecholaminergic polymorphic ventricular tachycardia. Accordingly, the addition of genetic testing to clinical data may be useful to identify the cause of the sudden death in this population. Mutations in the KCNQ1 encoded Kv7.1 channel are related to type 1 LQTS, familial atrial fibrillation (AF), short QT syndrome, and SCD. We present a clinical case where the presence of AF after resuscitation in a young man with cardiac arrest was the key clinical data to suspect an inherited disorder and genetic testing was the main determinant for identifying the cause of the cardiac arrest. The KCNQ1 p.Arg231His mutation explained the combined phenotype of AF and susceptibility to ventricular arrhythmias. The case highlights the importance of continued research in genetics and molecular mechanisms of channelopathies.

scholarly journals Novel SCN5A p.Val1667Asp Missense Variant Segregation and Characterization in a Family with Severe Brugada Syndrome and Multiple Sudden Deaths

2021 ◽  
Vol 22 (9) ◽  
pp. 4700
Author(s):  
Michelle M. Monasky ◽  
Emanuele Micaglio ◽  
Giuseppe Ciconte ◽  
Ilaria Rivolta ◽  
Valeria Borrelli ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Family History ◽  
Risk Stratification ◽  
Brugada Syndrome ◽  
Electrophysiological Study ◽  
Functional Characterization ◽  
The Family ◽  
Novel Variant ◽  
History Of ◽  
Scn5a Gene

Genetic testing in Brugada syndrome (BrS) is still not considered to be useful for clinical management of patients in the majority of cases, due to the current lack of understanding about the effect of specific variants. Additionally, family history of sudden death is generally not considered useful for arrhythmic risk stratification. We sought to demonstrate the usefulness of genetic testing and family history in diagnosis and risk stratification. The family history was collected for a proband who presented with a personal history of aborted cardiac arrest and in whom a novel variant in the SCN5A gene was found. Living family members underwent ajmaline testing, electrophysiological study, and genetic testing to determine genotype-phenotype segregation, if any. Patch-clamp experiments on transfected human embryonic kidney 293 cells enabled the functional characterization of the SCN5A novel variant in vitro. In this study, we provide crucial human data on the novel heterozygous variant NM_198056.2:c.5000T>A (p.Val1667Asp) in the SCN5A gene, and demonstrate its segregation with a severe form of BrS and multiple sudden deaths. Functional data revealed a loss of function of the protein affected by the variant. These results provide the first disease association with this variant and demonstrate the usefulness of genetic testing for diagnosis and risk stratification in certain patients. This study also demonstrates the usefulness of collecting the family history, which can assist in understanding the severity of the disease in certain situations and confirm the importance of the functional studies to distinguish between pathogenic mutations and harmless genetic variants.

scholarly journals Serial Observations and Mutational Analysis of an Adoptee with Family History of Hypertrophic Cardiomyopathy

2010 ◽  
Vol 2010 ◽  
pp. 1-4
Author(s):  
Bronwyn Harris ◽  
Jean P. Pfotenhauer ◽  
Cheri A. Silverstein ◽  
Larry W. Markham ◽  
Kim Schafer ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Hypertrophic Cardiomyopathy ◽  
Family History ◽  
Mutational Analysis ◽  
Clinical Findings ◽  
Dominant Mode ◽  
Natural Mother ◽  
History Of ◽  
In Cis ◽  
Inherited Cardiac Disease

Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disease with an autosomal dominant mode of transmission. Comprehensive genetic screening of several genes frequently found mutated in HCM is recommended for first-degree relatives of HCM patients. Genetic testing provides the means to identify those at risk of developing HCM and to institute measures to prevent sudden cardiac death (SCD). Here, we present an adoptee whose natural mother and maternal relatives were known be afflicted with HCM and SCD. The proband was followed closely from age 6 to 17 years, revealing a natural history of the progression of clinical findings associated with HCM. Genetic testing of the proband and her natural mother, who is affected by HCM, revealed that they were heterozygous for both the R719Q and T1513S variants in the cardiac beta-myosin heavy chain (MYH7) gene. The proband's ominous family history indicates that the combination of the R719Q and T1513S variantsin cismay be a “malignant” variant that imparts a poor prognosis in terms of the disease progression and SCD risk.

scholarly journals Cancer Previvors in an Active Duty Service Women Population: An Opportunity for Prevention and Increased Force Readiness

2020 ◽  
Author(s):  
Leann A Lovejoy ◽  
Clesson E Turner ◽  
Craig D Shriver ◽  
Rachel E Ellsworth
Keyword(s):  
Genetic Testing ◽  
Family History ◽  
High Risk ◽  
Cancer Predisposition ◽  
Clinical Genetic ◽  
High Risk Women ◽  
Clinical Genetic Testing ◽  
Pathogenic Mutations ◽  
History Of ◽  
Risk Reducing

Abstract Background The majority of active duty service women (ADS) are young, have access to healthcare, and meet fitness standards set by the U.S. military, suggesting that ADS represent a healthy population at low risk of cancer. Breast cancer is, however, the most common cancer in ADS and may have a significant effect on troop readiness with lengthy absence during treatment and inability to return to duty after the treatment. The identification of unaffected ADS who carry germline mutations in cancer predisposition genes (“previvors”) would provide the opportunity to prevent or detect cancer at an early stage, thus minimizing effects on troop readiness. In this study, we determined (1) how many high-risk ADS without cancer pursued genetic testing, (2) how many previvors employed risk-reducing strategies, and (3) the number of undiagnosed previvors within an ADS population. Methods The Clinical Breast Care Project (protocol WRNMMC IRB #20704) database of the Murtha Cancer Center/Walter Reed National Military Medical Center was queried to identify all ADS with no current or previous history of cancer. Classification as high genetic risk was calculated using National Comprehensive Cancer Network 2019 guidelines for genetic testing for breast, ovary, colon, and gastric cancer. The history of clinical genetic testing and risk-reducing strategies was extracted from the database. Genomic DNA from ADS with blood specimens available for research purposes were subjected to next-generation sequencing technologies using a cancer predisposition gene panel. Results Of the 336 cancer-free ADS enrolled in the Clinical Breast Care Project, 77 had a family history that met National Comprehensive Cancer Network criteria for genetic testing for BRCA1/2 and 2 had a family history of colon cancer meeting the criteria for genetic testing for Lynch syndrome. Of the 28 (35%) high-risk women who underwent clinical genetic testing, 11 had pathogenic mutations in the breast cancer genes BRCA1 (n = 5), BRCA2 (n = 5), or CHEK2 (n = 1). Five of the six ADS who had a relative with a known pathogenic mutation were carriers of the tested mutation. All of the women who had pathogenic mutations detected through clinical genetic testing underwent prophylactic double mastectomy, and three also had risk-reducing salpingo-oophorectomy. Two (6%) of the 33 high-risk ADS tested only in the research setting had a family history of breast/ovarian cancer and carried pathogenic mutations: one carried a BRCA2 mutation, whereas the other carried a mutation in the colon cancer predisposition gene PMS2. No mutations were detected in the 177 low-risk women tested in the research setting. Discussion Within this unaffected cohort of ADS, 23% were classified as high risk. Although all of the previvors engaged in risk-reduction strategies, only one-third of the high-risk women sought genetic testing. These data suggest that detailed family histories of cancer should be collected in ADS and genetic testing should be encouraged in those at high risk. The identification of previvors and concomitant use of risk-reduction strategies may improve health in the ADS and optimize military readiness by decreasing cancer incidence.

Sporadic Pick's Disease in a 28-Year-Old Woman

1993 ◽  
Vol 162 (2) ◽  
pp. 259-262 ◽  
Author(s):  
H. Rana Mowadat ◽  
E. E. Kerr ◽  
D. Stclair
Keyword(s):  
Family History ◽  
Psychiatric Disorder ◽  
Neurodegenerative Disorders ◽  
Young Patients ◽  
Initial Diagnosis ◽  
Cognitive Testing ◽  
Pick's Disease ◽  
Pick’S Disease ◽  
Functional Psychosis ◽  
History Of

Pick's disease was diagnosed in a 28-year-old woman without a family history of dementia (or other psychiatric disorder), after an initial diagnosis of functional psychosis and management with ECT and neuroleptics. The case illustrates the need for detailed neurological and cognitive testing and consideration of neurodegenerative disorders even in young patients.

scholarly journals Catheter ablation for atrial fibrillation in very young patients

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
K Yalin ◽  
B Ikitimur ◽  
T Aksu ◽  
AU Soysal ◽  
E Lyan ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Pulmonary Vein ◽  
Accessory Pathway ◽  
Young Patients ◽  
Old Patients ◽  
Index Procedure ◽  
Holter Ecg ◽  
History Of

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Pulmonary vein automaticity is an established trigger of paroxysmal atrial fibrillation (PAF) making pulmonary vein isolation (PVI)  the cornerstone for catheter ablation. However, data on triggers of AF and catheter ablation strategy in very young (&lt;30 years old) patients are sparse. Methods and results: Sixteen young patients (mean age 25.2 ± 4.9 years; 75% men) with recurrent drug refractory PAF underwent EP study and ablation at 3 EP centers. None of the patients had structural heart disease or family history of AF. EP study revealed degeneration of induced supraventricular tachycardia (SVT) into AF in 5 patients (n = 5, 31.2%). Induced SVTs were left lateral concealed accessory pathway mediated orthodromic AVRT in two patients, typical AVNRT in two patients, and left superior PV tachycardia in one patient respectively. In patients with induced SVTs, SVT ablation without PVI was performed as an index procedure. Remaining patients underwent second generation cryoballoon (CB-2) based PVI (n = 11, 68.7%). There were no major complications related to ablation procedures. Follow-up was based on outpatient visits including 24-h Holter-ECG at 3, 6 and, 12 months post ablation, or additional Holter-ECG was ordered in case of symptoms suggesting recurrence. Recurrence was defined as any atrial tachyarrhythmia (ATA) episode &gt;30s following a 3-month blanking period. After a median follow-up of 18.3 ± 6.2 months, 13 of 16 (81.2%) patients were free of ATA recurrence. None of the patients belonging to SVT ablation only group experienced ATA recurrence. Three patients with previous CB-2 PVI recurred, one had typical atrial flutter and underwent CTI ablation, remaining 2 patients had AF recurrence and medically followed. Conclusion In a considerable fraction of young adult patients with history of PAF SVTs may be responsible and SVT ablation without PVI may be sufficient as an index procedure. Catheter ablation AF seems to be safe and effective in this population.

scholarly journals Younger age of patients with myocardial infarction correlates with higher number of relatives with history of premature atherosclerosis

2020 ◽  
Author(s):  
Michał Ambroziak ◽  
Katarzyna Niewczas-Wieprzowska ◽  
Agnieszka Maicka ◽  
Andrzej Budaj
Keyword(s):  
Myocardial Infarction ◽  
Family History ◽  
Young Patients ◽  
Significant Risk ◽  
Control Group ◽  
Premature Coronary Artery Disease ◽  
Premature Atherosclerosis ◽  
Global Issues ◽  
Younger Age ◽  
History Of

Abstract Background. Premature coronary artery disease belongs to the most pressing global issues in a modern cardiology. Family history appears to be one of the most important and significant risk factors in young patients with myocardial infarction (MI). The aim of the study was to investigate the role of family history of premature cardiovascular disease (CVD) in patients <50 years with myocardial infarction (MI) compared to patients ≥ 50 years with MI and to young healthy people.Methods. The studied group (MI<50) consisted of 240 patients aged 26-49 years with MI. The control groups consisted of 240 patients (MI≥50) with MI aged 50-92 years and 240 healthy people aged 30-49 years.Results. There were statistically significant differences between the MI<50 and MI≥50 and young healthy groups regarding family history of premature MI/ischaemic stroke and percent of patients with of ≥2 relatives affected including parents, children, siblings, siblings of parents and grandparents (10.8%, 2.9%, 3.7%, respectively; p<0.0001). There was a statistically significant negative correlation between the age of the first episode of MI and the number of relatives with a history of premature MI/stroke (r=0.249, p<0.05) within all MI patients. Statistically significant differences between MI<50 and MI≥50 groups as well as young healthy control group were revealed regarding prevalence of smoking, body mass index (BMI), LDL, HDL, triglycerides (TG) and glucose levels.Conclusions. Younger age of patients with myocardial infarction correlates with a higher number of relatives with a history of premature MI/ischemic stroke. Thus, the family history of premature atherosclerosis involving not only the first-, but also the second-degree relatives, seems to be valuable and could be considered in an individual CVD risk evaluation in young people.

632 Family History of Children Diagnosed with Obstructive Sleep Apnea

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A248-A248
Author(s):  
Kristi Porterfield-Pruss ◽  
Denise Willis ◽  
Beverly Spray ◽  
Supriya Jambhekar
Keyword(s):  
Family History ◽  
Family Members ◽  
Biological Father ◽  
Medical Problems ◽  
Obstructive Sleep ◽  
Familial Association ◽  
History Of ◽  
The Mean ◽  
Relationship Of ◽  
The Relationship

Abstract Introduction Limited evidence suggests a familial association of OSA. It is not known how often children who require positive airway pressure (PAP) devices have a family member with OSA or that requires PAP. It is felt that PAP adherence in children is affected by PAP adherence in parents. We wanted to explore the relationship of OSA in children requiring PAP to OSA in immediate family members as well as the association of obesity and adherence between children and family members. Methods Caregivers of children who utilize PAP devices at home were invited to complete an electronic questionnaire regarding family history of OSA. Descriptive statistics were utilized to summarize results. Results The study was completed by 75 participants. The majority of children were male (64%, 48/75), black (47%, 35/75) and non-Hispanic (88%, 66/75). The mean age was 11.8 years (median 13) and mean BMI was 32.8 (median 29.8). The mean AHI on the diagnostic polysomnogram was 28.4 events per hour (median 15.3). Mean adherence to PAP &gt; 4 hours per night was 56.5 (Median 68.2). Most, 87% (65/75), have other underlying medical problems. Twenty-four percent (18/75) have a biological father with OSA of whom 61% (11/18) are considered moderately/extremely obese. Of mothers, 13% (10/75) have OSA and 70% (7/10) are obese. Overall, 29% (22/75) had either a paternal (11%, 8/75) or maternal (19%, 14/75) grandfather with OSA of which 36% (8/22) are obese. For grandmothers, 31% (23/75) have OSA and 22% (5/23) are obese with more being paternal (19%, 14/75) compared to maternal (12%, 9/75). Of the 73 total family members reported to have OSA, 86% (63/73) use PAP and most (65%, 41/63) use it for &gt; 4 hours every night. Few participants had siblings with OSA. Conclusion There were more fathers with OSA than mothers, but mothers were reported to be obese more often. Grandparents were reported to have OSA but were reported to be obese less often than parents. Maternal grandparents with OSA were reported to be obese more than paternal grandparents. The majority of family members with OSA who use CPAP report nightly use. Support (if any):

Abstract 16468: Results of Research Genetic Testing in Pediatric Cardiomyopathy Patients Justify Broader Clinical Genetic Testing

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Stephanie M Ware ◽  
Steven E Lipshultz ◽  
Steven D Colan ◽  
Ling Shi ◽  
Charles E Canter ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Family History ◽  
Risk Stratification ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Genetic ◽  
Clinical Genetic Testing ◽  
Whole Exome ◽  
Pediatric Cardiomyopathy ◽  
History Of

Introduction: Pediatric cardiomyopathies are genetically heterogeneous diseases with high risk of death or cardiac transplant. Despite progress in identifying causes, the majority of cases remain idiopathic. Currrently, genetic testing is not performed in all children with cardiomyopathy. Gene identification leads to better individual risk stratification and has the potential to stimulate the development of therapies based on the underlying mutation. The aim of this study is to identify genetic mutations in pediatric cardiomyopathy patients using whole exome sequencing. Hypothesis: Sarcomeric mutations are under-diagnosed causes of all forms of cardiomyopathy in children. Methods: Probands with cardiomyopathy were recruited from 11 institutions. Results of clinical genetic testing prior to enrollment were collected. Whole exome sequencing was performed and mutations were identified in 35 genes currently available on clinical genetic testing panels. Results: The initial 154 probands subjected to exome included 78 patients with DCM, 43 with HCM, 14 with RCM, and 19 with LVNC, mixed, or unknown types. Familial disease was present in 38% and the remainder were idiopathic. Twenty-seven percent had positive clinical genetic testing prior to enrollment. Exome testing identified mutations in 38 subjects who had not had clinical testing, increasing the cohort positive testing rate to 55% (DCM, 34.6%; HCM, 74.4%; RCM, 71.4%). Forty-five percent of subjects with no family history of disease had an identifiable mutation. Conclusions: Pediatric cardiomyopathy patients have a high incidence of mutations that can be identified by clinically available genetic testing. Lack of a family history of cardiomyopathy was not predictive of normal genetic testing. These results support the broader use of genetic testing in pediatric patients with all functional phenotypes of cardiomyopathy to identify disease causation allowing better family risk stratification.

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