Genetic variants for long QT syndrome among infants and children from a statewide newborn hearing screening program cohort

J Pediatr. 2014 Mar;164(3):590-5.e1-3. doi: 10.1016/j.jpeds.2013.11.011. Epub 2013 Dec 31.


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 ≤ 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.

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 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alternative Splicing
  • Child, Preschool
  • Electrocardiography
  • Genetic Testing
  • Hearing Loss / diagnosis
  • Hearing Loss / genetics
  • Heterozygote
  • Humans
  • Infant
  • Infant, Newborn
  • Jervell-Lange Nielsen Syndrome / genetics
  • KCNQ1 Potassium Channel / genetics*
  • Long QT Syndrome / genetics*
  • Mutation
  • NAV1.5 Voltage-Gated Sodium Channel / genetics*
  • Neonatal Screening*
  • Polymorphism, Genetic
  • Prospective Studies


  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human
  • NAV1.5 Voltage-Gated Sodium Channel
  • SCN5A protein, human