The Jervell and Lange-Nielsen syndrome: natural history, molecular basis, and clinical outcome.
BACKGROUND
Data on the Jervell and Lange-Nielsen syndrome (J-LN), the long-QT syndrome (LQTS) variant associated with deafness and caused by homozygous or compound heterozygous mutations on the KCNQ1 or on the KCNE1 genes encoding the I(Ks) current, are still based largely on case reports.


RESULTS
We analyzed data from 186 J-LN patients obtained from the literature (31%) and from individual physicians (69%). Most patients (86%) had cardiac events, and 50% were already symptomatic by age 3. Their QTc was markedly prolonged (557+/-65 ms). Most of the arrhythmic events (95%) were triggered by emotions or exercise. Females are at lower risk for cardiac arrest and sudden death (CA/SD) (hazard ratio, 0.54; 95% CI, 0.34 to 0.88; P=0.01). A QTc >550 ms and history of syncope during the first year of life are independent predictors of subsequent CA/SD. Most mutations (90.5%) are on the KCNQ1 gene; mutations on the KCNE1 gene are associated with a more benign course. beta-Blockers have only partial efficacy; 51% of the patients had events despite therapy and 27% had CA/SD.


CONCLUSIONS
J-LN syndrome is a most severe variant of LQTS, with a very early onset and major QTc prolongation, and in which beta-blockers have limited efficacy. Subgroups at relatively lower risk for CA/SD are identifiable and include females, patients with a QTc < or =550 ms, those without events in the first year of life, and those with mutations on KCNE1. Early therapy with implanted cardioverter/defibrillators must be considered.
Schwartz
Peter J
PJ
Department of Cardiology, University of Pavia, IRCCS Policlinico S. Matteo, Pavia, Italy. pjqt@compuserve.com
Spazzolini
Carla
C
Crotti
Lia
L
Bathen
Jørn
J
Amlie
Jan P
JP
Timothy
Katherine
K
Shkolnikova
Maria
M
Berul
Charles I
CI
Bitner-Glindzicz
Maria
M
Toivonen
Lauri
L
Horie
Minoru
M
Schulze-Bahr
Eric
E
Denjoy
Isabelle
I
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D003625:Data Collection; D005192:Family Health; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D029593:Jervell-Lange Nielsen Syndrome / Q000209:etiology / Q000235:genetics / Q000401:mortality / Q000628:therapy; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D008297:Male; D008875:Middle Aged; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D012737:Sex Factors; D016019:Survival Analysis; D016896:Treatment Outcome
C489622:KCNE1 protein, human; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D024642:Potassium Channels, Voltage-Gated