Genetic Variants for Long QT Syndrome among Infants and Children from a Statewide Newborn Hearing Screening Program Cohort

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• 作者：Ruey-Kang R. Chang ; MD ; MPH¹ ; ^{rkchang@labiomed.org" class="auth_mail} ; Yueh-Tze Lan ; MD² ; Michael J. Silka ; MD³ ; Hallie Morrow ; MD⁴ ; Alan Kwong ; MS¹ ; Janna Smith-Lang ; PhD² ; Robert Wallerstein ; MD² ; Henry J. Lin ; MD¹
• 关键词：bpm ; Beats/min ; ECG ; Electrocardiogram ; JLNS ; Jervell and Lange-Nielsen syndrome ; LQTS ; Long QT syndrome ; NHSP ; Newborn Hearing Screening Program ; QTc ; Heart rate corrected QT ; SNHL ; Sensorineural hearing loss
• 刊名：The Journal of Pediatrics
• 出版年：March, 2014
• 年：2014
• 卷：164
• 期：3
• 页码：590-595.e3
• 全文大小：1067 K

文摘

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Objectives

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.

Study design

In California, we conducted statewide, prospective ECG screening of children 鈮? 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 鈮?50 ms had repeat ECGs. DNA sequencing of 12 LQTS genes was performed for repeat QTc intervals 鈮?50 ms.

Results

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聽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.Glu449Argfs*14; c.1590+1G>A or p.Glu530sp) and 1 in SCN5A (c.5872C>T or p.Arg1958*).

Conclusions

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.