Congenital long QT syndrome (LQTS) is a disease characterized by prolongation of ventricle repolarization and by the occurrence, usually during emotional or physical stress, of life-threatening arrhythmias that lead to sudden death in most symptomatic and untreated patients. Two variants have been initially identified:the original Jervell and Lange-Nielsen syndrome of congenital deafness and autosomal recessive inheritance, and the more frequent Romano-Ward syndrome of autosomal dominant inheritance. Evidence also shows that approximately 25 to 30% of the cases are sporadic with syncope and a prolonged QT interval but without showing evidence for familial involvement. Familial and sporadic cases have been grouped under the definition of congenital long QT syndrome. We experienced a case of congenital long QT syndrome in a 13-year-old female girl. She had episodes of recurrent syncope and QT interval prolongation(QTc=0.46sec) in electrocardiogram(ECG). The ECG of her mother showed QT interval prologation(QTc=0.46sec). After applying atenolol, the QT interval returned to normal range and syncope has not occurred. We report a case of congenital long QT syndrome with a brief review of related literatures.
Adolescent ; Arrhythmias, Cardiac ; Atenolol ; Deafness ; Death, Sudden ; Electrocardiography ; Female ; Humans ; Jervell-Lange Nielsen Syndrome ; Long QT Syndrome* ; Mothers ; Reference Values ; Romano-Ward Syndrome ; Syncope* ; Wills

Congenital long QT syndrome (LQTS) is an inherited disease characterized by prolonged QT intervals and polymorphic ventricular tachycardia. The clinical manifestations vary from sudden cardiac death by ventricular arrhythmia to asymptom throughout life. In 1957, Jervell and Lange-Nielsen reported a syndrome of congen-ital sensory deafness associated with a prolonged QT interval in four children. The affected children had multiple syncopal episodes, and three died suddenly. The mode of inheritance is autosomal recessive. Affected persons are susceptible to recurrent syncope, and they have a high incidence of sudden death and short life expectancy. We report a case and review the literature on long QT syndrome diagnosed in a 30-year-old female with a history of convulsion and loss of consciousness during delivery.
Adult ; Arrhythmias, Cardiac ; Child ; Deafness* ; Death, Sudden ; Death, Sudden, Cardiac ; Female ; Humans ; Incidence ; Jervell-Lange Nielsen Syndrome ; Life Expectancy ; Long QT Syndrome* ; Seizures ; Syncope* ; Tachycardia, Ventricular ; Unconsciousness ; Wills

OBJECTIVEJervell and Lange-Nielsen syndrome (JLNS) is a severe cardioauditory syndrome manifested as QT interval prolongation, abnormal T waves, and relative bradycardia ventricular tachyarrhythmias. In this report, we screened a nonconsanguineous families with JLNS for mutations in KCNQ1.

METHODSMutation analysis was performed by using purified PCR products to direct sequence analysis on an ABI-3730XL automated DNA sequencer. The whole sequence of proband' KCNQ1 was screened firstly, then screened the mutation exon sequences of others of the family and 50 unrelated normal persons.

RESULTSA heterogeneous mutation was identified in the patients of the JLNS family, a missense mutation (G-->T) at nucleotide 917 encoded in exon 6 of KCNQ1. This substitution leads to a change from glycine to Valine at codon 306(G306V) corresponding to the S5 transmembrane segment of KCNQ1. The other normal members of the family and 50 unrelated normal persons were not identified this mutation.

CONCLUSIONThe result suggested that not only homozygous mutations or compound heterozygous mutations in KCNQ1 could cause Jervell-Lange-Nielsen syndrome, the single heterozygous mutation may also cause Jervell-Lange-Nielsen syndrome.

Adolescent ; Adult ; Aged ; Child ; Female ; Genotype ; Humans ; Jervell-Lange Nielsen Syndrome ; genetics ; KCNQ1 Potassium Channel ; genetics ; Long QT Syndrome ; genetics ; Male ; Middle Aged ; Mutation, Missense ; Pedigree ; Young Adult

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 beta-blocker therapy the patient has remained symptom-free for three and a half years.
Asian Continental Ancestry Group/*genetics ; Child, Preschool ; Electrocardiography ; Exons ; Family ; Gene Deletion ; Heterozygote ; Humans ; Jervell-Lange Nielsen Syndrome/diagnosis/*genetics ; KCNQ1 Potassium Channel/*genetics ; Male ; Mutation ; Pedigree ; Republic of Korea

Long QT syndrome (LQTS) is a genetically heterogeneous disorder associated with sequence variations in more than 10 genes; in some cases, it is caused by large deletions or duplications among the main, known LQTS-associated genes. Here, we describe a 14-month-old Korean boy with congenital hearing loss and prolonged QT interval whose condition was clinically diagnosed as Jervell and Lange-Nielsen syndrome (JLNS), a recessive form of LQTS. Genetic analyses using sequence analysis and multiplex ligation-dependent probe amplification (MLPA) assay revealed a large deletion spanning exons 7-10 as well as a frameshift mutation (c.1893dup; p.Arg632Glnfs*20). To our knowledge, this is the first report of a large deletion in KCNQ1 identified in JLNS patients. This case indicates that a method such as MLPA, which can identify large deletions or duplications needs to be considered in addition to sequence analysis to diagnose JLNS.
Adolescent ; Alleles ; Base Sequence ; Electrocardiography ; Exons ; Frameshift Mutation ; Heterozygote ; Humans ; Jervell-Lange Nielsen Syndrome/diagnosis/*genetics ; KCNQ1 Potassium Channel/*genetics ; Male ; Nucleic Acid Amplification Techniques ; Pedigree ; Sequence Analysis, DNA ; Sequence Deletion

OBJECTIVETo investigate the molecular pathology in families with long QT syndrome (LQTS) including Jervell-Longe-Nielsen syndrome (JLNS) and Romano-ward syndrome (RWS) and Brugada syndrome (BS) in Chinese population.

METHODSPolymerase chain reaction and DNA sequencing were used to screen for KCNQ1, KCNH2, KCNE1, and SCN5A mutation.

RESULTSWe identified a novel mutation N1774S in the SCN5A gene of the BS family, a novel mutation G314S in a RWS family which had also been found in Europe, North America, and Japan, and a single nucleotide polymorphisms (SNPs) G643S in the KCNQ1 of the JLNS family. In this JLNS family, another heterozygous novel mutation in exon 2a was found in KCNQ1 of the patients.

CONCLUSIONNew mutations were found in our experiment, which expand the spectrum of KCNQ1 and SCN5A mutations that cause LQTS and BS.

Adolescent ; Adult ; Base Sequence ; ERG1 Potassium Channel ; Ether-A-Go-Go Potassium Channels ; genetics ; Female ; Humans ; Jervell-Lange Nielsen Syndrome ; genetics ; KCNQ1 Potassium Channel ; genetics ; Long QT Syndrome ; congenital ; genetics ; Male ; Middle Aged ; Molecular Sequence Data ; Muscle Proteins ; genetics ; Mutation ; NAV1.5 Voltage-Gated Sodium Channel ; Pedigree ; Potassium Channels, Voltage-Gated ; genetics ; Romano-Ward Syndrome ; genetics ; Sodium Channels ; genetics