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: 7826423
• 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 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7826423
• 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）： 该应用是对RFA-09-09-003的回应，并解决了广泛的挑战领域（15）转化科学和特定挑战主题，15-OD（ORDR）-101：预防，早期发现和治疗罕见疾病的试点项目。先天性长QT综合征（LQT）是一种遗传疾病，其特征是心电图（ECG）（ECG）和威胁生命的心律失常的QT间隔延长。 Jervell和Lange-Nielsen综合征（JLNS）是最严重的LQT形式，具有先天性感觉神经听力损失（SNHL）的标志性特征。 JLNS患者很早就会发生症状，如果未治疗，则有猝死的风险。未经诊断JLN的婴儿猝死通常被报道为猝死综合征（SIDS）。虽然对JLN的普通人群进行大规模筛查是不切实际的，但据报道，先天性SNHL的年龄较大儿童的JLN患病率高达4％。因此，大多数患有SNHL的婴儿现在都被州新生儿听力筛查计划确定，因此为JLN的早期发现和治疗创造了机会。我们通过对新生儿听力筛查计划鉴定的严重至关重要的SNHL的婴儿进行心脏筛查，提出一种创新的JLNS诊断方法。这项研究的目的是确定严重至可靠的SNHL婴儿的JLN的患病率，并评估早期JLNS诊断的有效性。我们提出了一项基于人群的研究，该研究通过加利福尼亚新生儿听力筛查计划确定了SNHL的婴儿。将招募受试者进行“前瞻性队列”（项目期间的SNHL诊断）和“回顾性队列”（前4年的SNHL诊断）。估计有1,256名患有严重至关格的SNHL的婴儿和幼儿将参加这项为期两年的研究。心脏筛查将包括详细的个人和家族史以及12铅ECG。被认为是高风险的受试者将对JLNS突变进行基因检测。从前瞻性队列中，我们将计算出严重至关重要的SNHL的幼儿JLN的患病率，并将其与年龄较大的儿童的报告率进行比较。由于早期诊断的结果，将由接受治疗的婴儿（€blockers和/或植入植入的心脏逆变器解除剂（ICD））评估早期JLN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估心脏筛查的有效性，以确定如果回顾性队列早期进行心脏筛查，可以预防的心脏死亡和SID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，具有感官听力损失的标志性。 JLN的患者在生命的早期就会成为症状，如果未被诊断为早期诊断并得到适当治疗，则有猝死的风险。我们提出了一种创新的方法，可以通过对加利福尼亚新生儿听力筛查计划中所有识别出具有感觉性听力损失的婴儿的心脏筛查来对JLN进行早期诊断。