Screening for Jervell and Lange-Nielsen Syndrome

杰维尔综合症和兰格-尼尔森综合症筛查

• 批准号: 7934628
• 负责人: RUEY-KANG R CHANG
• 金额: $ 50万
• 依托单位: LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7934628
• 关键词: Address; Affect; Age-Months; Anatomy; Area; Arrhythmia; Autopsy; California; Cardiac; Cardiac Death; Cessation of life; Child; Clinical Management; Data; Diagnosis; Early Diagnosis; Effectiveness; Electrocardiogram; Family history of; General Population; Genetic screening method; Goals; Hereditary Disease; Implantable Defibrillators; Individual; Infant; Jervell-Lange Nielsen Syndrome; Life; Long QT Syndrome; Mass Screening; Mutation; Neonatal Screening; Newborn Infant; Patients; Pilot Projects; Prevalence; Prevention; Rare Diseases; Recording of previous events; Recruitment Activity; Registries; Reporting; Risk; Screening procedure; Sensorineural Hearing Loss; Sudden infant death syndrome; Syndrome; Translational Research; Ventricular Arrhythmia; base; cohort; hearing impairment; hearing screening; high risk; infancy; infant death; innovation; outcome forecast; population based; prevent; programs; prospective; public health relevance; response; success; sudden cardiac death

DESCRIPTION (provided by applicant): This application is in response to RFA-09-09-003 and addresses broad Challenge Area (15) Translational Science and specific Challenge Topic, 15-OD(ORDR)-101: Pilot Projects for Prevention, Early Detection, and Treatment of Rare Diseases. The congenital long QT syndrome (LQTS) is a genetic disorder characterized by a prolonged QT interval on the electrocardiogram (ECG) and life-threatening arrhythmias. The Jervell and Lange-Nielsen syndrome (JLNS) is the most severe form of LQTS, with a hallmark feature of congenital sensorineural hearing loss (SNHL). JLNS patients become symptomatic very early and are at risk for sudden cardiac death if untreated. Sudden cardiac death of infants with undiagnosed JLNS is often reported as sudden infant death syndrome (SIDS). While mass screening of the general population for JLNS is not practical, the prevalence of JLNS in older children with congenital SNHL has been reported as high as 4%. Most infants with SNHL are now identified early by the state newborn hearing screening programs, therefore, creates an opportunity for early detection and treatment of JLNS. We propose an innovative approach to early JLNS diagnosis by cardiac screening of infants with severe-to-profound SNHL identified by the newborn hearing screening program. The goals of this study are to determine the prevalence of JLNS in infants with severe-to-profound SNHL and to evaluate the effectiveness of early JLNS diagnosis. We propose a population-based study of infants with SNHL identified through the California Newborn Hearing Screening Program. Subjects will be recruited for a "prospective cohort" (SNHL diagnosed during the project period) and a "retrospective cohort" (SNHL diagnosed in preceding 4 years). An estimated 1,256 infants and young children with severe-to-profound SNHL will participate in this 2-year study. Cardiac screening will consist of detailed personal and family histories, and a 12-lead ECG. Subjects who are considered high risk will have genetic testing for JLNS mutations. From the prospective cohort, we will calculate the prevalence rate of JLNS among young infants with severe-to-profound SNHL and compared with the reported rates in older children. The impact of early JLNS diagnosis on clinical management will be assessed by the number of infants who receive therapy [¿-blockers and/or an implantable cardioverter-defibrillator (ICD)] as a result of early diagnosis. The effectiveness of cardiac screening will be evaluated by comparing the retrospective cohort and the prospective cohort to determine the number of cardiac deaths and SIDS that could have been prevented had the cardiac screening been conducted early in the retrospective cohort. Public Health Relevance: The Jervell and Lange-Nielsen syndrome (JLNS) is the most severe form of the congenital long QT syndrome with a hallmark feature of sensorineural hearing loss. Patients with JLNS become symptomatic early in life and are at risk for sudden cardiac death if they are not diagnosed early and properly treated. We propose an innovative approach to early diagnosis of JLNS by cardiac screening of all infants who are identified with sensorineural hearing loss by the California Newborn Hearing Screening Program.

描述（由申请人提供）： 本申请是对RFA-09-09-003的回应，并解决了广泛的挑战领域（15）转化科学和特定的挑战主题，15-OD（ORR）-101：罕见疾病预防、早期检测和治疗的试点项目。先天性长QT综合征（LQTS）是一种遗传性疾病，其特征是心电图（ECG）上QT间期延长和危及生命的心律失常。Jervell和Lange-Nielsen综合征（JLNS）是LQTS最严重的形式，具有先天性感音神经性听力损失（SNHL）的标志性特征。JLNS患者很早就出现症状，如果不治疗，有心脏性猝死的风险。未确诊的JLNS婴儿的心源性猝死通常被报告为婴儿猝死综合征（SIDS）。虽然对一般人群进行JLNS的大规模筛查并不实际，但据报道，患有先天性SNHL的大龄儿童中JLNS的患病率高达4%。大多数患有SNHL的婴儿现在都能通过国家新生儿听力筛查计划早期发现，因此，为早期发现和治疗JLNS创造了机会。我们提出了一种创新的方法，通过对新生儿听力筛查计划确定的重度至极重度SNHL婴儿进行心脏筛查来早期诊断JLNS。本研究的目的是确定重度至极重度SNHL婴儿中JLNS的患病率，并评估早期JLNS诊断的有效性。我们建议对通过加州新生儿听力筛查计划确定的SNHL婴儿进行一项基于人群的研究。将招募受试者进入“前瞻性队列”（项目期间诊断的SNHL）和“回顾性队列”（前4年诊断的SNHL）。估计有1，256名患有重度至重度SNHL的婴幼儿将参加这项为期2年的研究。心脏筛查将包括详细的个人和家族史以及12导联ECG。被认为是高风险的受试者将接受JLNS突变的基因检测。从前瞻性队列中，我们将计算重度至极重度SNHL幼儿中JLNS的患病率，并与大龄儿童中报告的患病率进行比较。将通过因早期诊断而接受治疗[β-受体阻滞剂和/或植入式心律转复除颤器（ICD）]的婴儿数量来评估早期JLNS诊断对临床管理的影响。将通过比较回顾性队列和前瞻性队列来评价心脏筛查的有效性，以确定如果在回顾性队列中早期进行心脏筛查，可以预防的心脏死亡和SIDS的数量。 公共卫生相关性： Jervell和Lange-Nielsen综合征（JLNS）是先天性长QT综合征的最严重形式，具有感音神经性听力损失的标志性特征。JLNS患者在生命早期就出现症状，如果没有及早诊断和适当治疗，就有心源性猝死的风险。我们提出了一种创新的方法，通过对所有被加州新生儿听力筛查计划确定为感音神经性听力损失的婴儿进行心脏筛查来早期诊断JLNS。