Jervell and Lange-Nielsen syndrome: A Norwegian perspective

Jervell and Lange-Nielsen syndrome (MIM 220400; JLNS), is a rare form of pr ofound congenital deafness combined with syncopal attacks and sudden death due to prolonged QTc; it is an autosomal recessive trait. After its first d escription in Norway in 1957, later reports from many other countries have confirmed its occurrence. Nowhere is the prevalence so high as in Norway, w here we estimate a prevalence of at least 1:200,000. The KCNQ1 and KCNE1 pr oteins coassemble in a potassium channel, and mutations in either the KCNQ1 gene or the KCNE1 gene disrupt endolymph production in the stria vasculari s in the cochlea, causing deafness. KCNQ1 seems to be the major gene in JLN S. Long QT syndrome (LQTS) is a separate disorder of either autosomal domin ant or recessive inheritance caused by mutations in four different ion chan nel genes; KCNQ1 is the one most frequently involved. Some heterozygous car riers of JLNS mutations in either gene may suffer from prolonged QTc and be symptomatic LQTS patients with a need for appropriate medical treatment to prevent life-threatening cardiac arrhythmia. In general, frameshift/stop m utations cause JLNS, and missense/splice site mutations cause LQTS, but a p recise genotype-phenotype correlation in LQTS and JLNS is not established, which complicates both genetic counseling and clinical risk evaluation in c arriers. We review JLNS from a Norwegian perspective because of the unusual ly high prevalence, the genetic homogeneity associated with considerable mu tational heterogeneity, and some evidence for recurrent mutational events a s well as one founder mutation. We outline the clinical implications for in vestigation of deaf children and cases of sudden infant death syndrome as w ell as careful electrocardiographic monitoring of identified mutation carri ers to prevent sudden death. (C) 2000 Wiley-Liss, Inc.