Department of Pediatrics, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, CA.
Santa Clara Valley Medical Center, San Jose, CA.
J Pediatr. 2014 Mar;164(3):590-5.e1-3. doi: 10.1016/j.jpeds.2013.11.011. Epub 2013 Dec 31.
Autosomal recessive long QT syndrome (LQTS), or Jervell and Lange-Nielsen syndrome (JLNS), can be associated with sensorineural hearing loss. We aimed to explore newborn hearing screening combined with electrocardiograms (ECGs) for early JLNS detection.
In California, we conducted statewide, prospective ECG screening of children ≤ 6 years of age with unilateral or bilateral, severe or profound, sensorineural or mixed hearing loss. Families were identified through newborn hearing screening and interviewed about medical and family histories. Twelve-lead ECGs were obtained. Those with positive histories or heart rate corrected QT (QTc) intervals ≥ 450 ms had repeat ECGs. DNA sequencing of 12 LQTS genes was performed for repeat QTc intervals ≥ 450 ms.
We screened 707 subjects by ECGs (number screened/number of responses = 91%; number of responses/number of families who were mailed invitations = 54%). Of these, 73 had repeat ECGs, and 19 underwent gene testing. No subject had homozygous or compound heterozygous LQTS mutations, as in JLNS. However, 3 individuals (with QTc intervals of 472, 457, and 456 ms, respectively) were heterozygous for variants that cause truncation or missplicing: 2 in KCNQ1 (c.1343dupC or p.Glu449Argfs14; c.1590+1G>A or p.Glu530sp) and 1 in SCN5A (c.5872C>T or p.Arg1958).
In contrast to reports of JLNS in up to 4% of children with sensorineural hearing loss, we found no examples of JLNS. Because the 3 variants identified were unrelated to hearing, they likely represent the prevalence of potential LQTS mutations in the general population. Further studies are needed to define consequences of such mutations and assess the overall prevalence.
常染色体隐性长 QT 综合征（LQTS），或杰尔维伦-兰格-尼尔森综合征（JLNS），可伴有感觉神经性听力损失。我们旨在探索新生儿听力筛查与心电图（ECG）相结合，以早期发现 JLNS。
在加利福尼亚州，我们对患有单侧或双侧、重度或极重度感觉神经性或混合性听力损失的≤ 6 岁儿童进行了全州范围的前瞻性心电图筛查。通过新生儿听力筛查确定患儿，对其家族进行医疗和家族病史询问。获取 12 导联心电图。对于有阳性病史或心率校正 QT（QTc）间期≥450 ms 的患儿，进行重复心电图检查。对于 QTc 间期≥450 ms 的患儿，进行 12 个 LQTS 基因的 DNA 测序。
我们通过心电图筛查了 707 例患儿（筛查例数/应答例数=91%；应答例数/受邀家族数=54%）。其中，73 例患儿进行了重复心电图检查，19 例患儿进行了基因检测。无患儿存在 JLNS 中所见的纯合或复合杂合性 LQTS 突变。然而，有 3 例患儿（分别为 QTc 间期为 472、457 和 456 ms）为导致截断或错义剪接的变异杂合子：2 例在 KCNQ1（c.1343dupC 或 p.Glu449Argfs14；c.1590+1G>A 或 p.Glu530sp），1 例在 SCN5A（c.5872C>T 或 p.Arg1958）。
与 JLNS 报告中高达 4%的感觉神经性听力损失患儿不同，我们并未发现 JLNS 的病例。由于鉴定出的 3 种变异与听力无关，因此它们可能代表一般人群中潜在 LQTS 突变的发生率。需要进一步研究来明确此类突变的后果并评估总体发生率。
