the congenital long qt syndrome ( lqts ) is a clinical disorder of genetic origin . it is characterized by abnormal qt interval prolongation ( rate - corrected qt or qtc ) and susceptibility to sudden death owing to a specific type of polymorphic ventricular tachycardia , torsade de pointes ( 1 ) . two forms of inherited lqts have been described : romano - ward syndrome ( rws ) , an autosomal dominant inherited disorder with prolongation of the qtc without other associated noncardiac abnormalities ( 1 ) , and jervell and lange - nielsen syndrome ( jlns ) , an autosomal recessive disorder with lqts associated with sensorineural deafness ( 2 ) . jlns usually results from homozygous loss - of - function mutations in either kcnq1 or kcne1 . furthermore , jlns accompanies complete loss of iks in hair cells and endolymph of the inner ear , which result in congenital deafness ( 3 ) . in this report , we describe the first case of genetically confirmed jlns in korea with compound heterozygous mutations in kcnq1 . in addition , one of the mutations is a novel splicing one , which has never been reported before . a five - year - old boy visited the hospital due to recurrent syncope on april 17 , 2006 . it involved seizure - like movement such as tonic - clonic activity , eyeball deviation , and loss of consciousness . they mostly occurred during walking or exercising , and continued for several seconds to several minutes ; but cardiac resuscitation had never been required . his past medical history revealed that he had undergone cochlear transplantation due to congenital sensorineural deafness . his resting 12-lead electrocardiogram ( ecg ) revealed a markedly prolonged qtc interval of 590 ms ( fig . 2 ) . at that time , he was not on drugs that could extend the duration of qt . nor did he have any electrolyte imbalance such as hypomagnesemia or hypocalcemia . because the diagnosis of lqts was established , an intracardiac electrophysiologic study was not performed . no family members had experienced syncope , palpitation , epilepsy , or any episode of cardiac arrest . the patient 's father and brother had normal qtc intervals , 434 ms and 404 ms , respectively , but his mother had a prolonged qtc interval of 473 ms . molecular genetic analysis revealed that the patient had compound heterozygous mutations in the kcnq1 gene . the other was a novel splicing mutation , c.921g > a , p.v307v ( fig . the allele frequency of the novel sequence variation c.921g > a was 0% in a group of 95 healthy controls . the nucleotide c.921 g is located at the end of exon 6 ; therefore , substitution of g to a was predicted to affect the splicing of mrna . to determine the effect of this novel substitution , we performed reverse transcription - polymerase chain reaction and detected an abnormally spliced 593-bp mrna product in which the exon 6 had been skipped ( fig . the subsequent segregation study detected c.828 - 830delctc heterozygous mutation in his mother , and c.921g > a in both his father and elder brother ( fig . -blocker therapy was initiated with oral propranolol ( 2 mg / kg / d ) . since then , he has remained symptom - free for three and a half years , although he has a persistent qt prolongation ( qtc=551 ms ) as of the most recent ecg . the cardiac delayed rectifier current ( ik ) is one of the major determinants of phase 3 repolarization of the cardiac action potential . it is composed of three independent components : an ultrarapid component , called ikur ; a rapid component , ikr ; and a slow and catecholamine - sensitive component , iks ( 4 ) . kcnq1 encodes the -subunit and kcne1 encodes the -subunit of the channel responsible for the voltage - dependent slowly activating delayed rectifier potassium channel . homozygous or compound heterozygous mutation in either kcnq1 or kcne1 ( mink ) causes the jervell and lange - nielsen autosomal recessive form of the disease ( jln1 and jln2 , respectively ) , which is characterized by cardiac phenotype ( long qt interval and susceptibility to ventricular arrhythmia ) and sensorineural deafness ( 5 , 6 ) . jlns is a very rare disease , found in less than 1% of all patients with lqts . moreover , only a few cases with compound heterozygous mutations have been reported ( 2 , 7 - 9 ) . in the present study , we described one korean family in which compound heterozygous mutations in kcnq1 resulted in jlns in the proband . our findings are the first in korea to demonstrate that compound heterozygote mutations in kcnq1 causes jnls . one of two mutant alleles has been associated with lqts ( 10 ) while the other was a novel sequence variant resulting in an abnormal splicing effect of exon 6 . most patients with jlns become symptomatic and they have a high risk of life - threatening arrhythmias despite treatment with -blockers ( 11 , 12 ) . furthermore , jlns patients suffer from cardiac events in the early period of their lives ( 11 ) . the high - risk group of patients with jlns includes those with a qtc interval exceeding 550 ms or syncope during early childhood ( birth to fourth year of life ) , males less than 20 yr old , and those with kcnq1 mutation ( 12 ) . the high - risk patients are strongly recommended implanted cardiac defibrillator ( icd ) therapy after the age of five , combined with early medical treatment ( 12 ) . although the family members of our jnls patient who have the same disease do not show any symptoms so far , they may need specific management including icd therapy or medical treatment to prevent a serious , life - threatening cardiac event . hence , it is important to perform genetic analysis and to determine whether they have jnls mutation . in general , heterozygous carriers of the jlns mutation are observed to be asymptomatic or mildly symptomatic . one study suggested an explanation for sush an observation that frameshift / truncating mutations are responsible for the majority of jlns ( 13 , 14 ) . frameshift / truncating mutations are unable to cause dominant - negative suppression under normal circumstances because they can not co - assemble with wild - type normal subunits . therefore , jlns mutations are milder , and therefore , in the heterozygous form , do little harm . in contrast , the missense mutation in the kcnq1 gene , which is most common in rws , can co - assemble with normal subunits , and thereby exert a dominant - negative suppression effect . despite limited data the patient 's father and brother with a truncating - like mutation have normal qtc interval , while his mother with a missense mutation has prolonged qtc interval . therefore , jlns requires complete gene screening of all family members even if they have normal qtc intervals . furthermore , the carriers need an individual risk evaluation and careful management depending on the type of mutation . a carrier with a missense mutation should be closely observed . in conclusion our report identified compound heterozygote deletion / splicing error mutations ( c.828 - 830 delctc , p.s277del / c.921g > a , p.v307v ) . to the best of our knowledge , functional assays of the novel mutation were not performed in our study and should be a subject for future research .
the jervell and lange - nielsen syndrome ( jlns ) is an autosomal recessive syndrome characterized by congenital deafness and cardiac phenotype ( qt prolongation , ventricular arrhythmias , and sudden death ) . 
 jlns has been shown to occur due to homozygous mutation in kcnq1 or kcne1 . 
 there have been a few clinical case reports on jlns in korea ; however , these were not confirmed by a genetic study . 
 we identified compound heterozygous mutations in kcnq1 in a 5-yr - old child with jlns , who visited the hospital due to recurrent syncope and seizures and had congenital sensorineural deafness . 
 his electrocardiogram revealed a markedly prolonged corrected qt interval with t wave alternans . 
 the sequence analysis of the proband revealed the presence of novel compound heterozygous deletion / splicing error mutations ( c.828 - 830 delctc , p.s277del / c.921g > a , p.v307v ) . 
 each mutation in kcnq1 was identified on the maternal and paternal side . with -blocker therapy 
 the patient has remained symptom - free for three and a half years .