Congenital deaf-mutism, functional heart disease with prolongation of the Q-T interval, and sudden death

A, Jervell; Lange-Nielsen, F

doi:10.1016/0002-8703(57)90079-0

Cited by 1,403 publications

(296 citation statements)

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“…Mutations in KCNQ1 cause the autosomal recessive Jervell and Lange‐Nielsen syndrome [MIM 220400], characterized by SNHL and cardiac abnormalities (long QT syndrome) (Jervell and Lange‐Nielsen, 1957; Neyroud et al, 1997). In this syndrome, there is an impaired K + secretion into the endolymph by the KCNQ1/KCNE1 channel complex on the apical membranes of the marginal cells in the stria vascularis, as confirmed in a mouse model with the homozygous mutants being completely deaf (Lee et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Examples of syndromic SNHL include Pendred's syndrome ([MIM 274600, www.omim.org/], combining hearing loss and goiter (Pendred, 1896; Bizhanova and Kopp, 2010)), Waardenburg syndrome [WS; hearing loss and pigmentation abnormalities (Waardenburg, 1951; Pingault et al, 2010)] and Jervell and Lange‐Nielsen syndrome ([MIM 220400 and MIM 612347], hearing loss and cardiac symptoms (Jervell and Lange‐Nielsen, 1957)). In nonsyndromic SNHL, associations with obvious abnormalities of the external ear or symptoms other than hearing loss cannot be found, but the heterogeneity of loci and genes is high: over 130 loci have been mapped and over 60 different genes have been implicated presently (van Camp and Smith).…”

Section: Introductionmentioning

confidence: 99%

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Development of the stria vascularis and potassium regulation in the human fetal cochlea: Insights into hereditary sensorineural hearing loss

Locher

Groot

Iperen

et al. 2015

Developmental Neurobiology

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Sensorineural hearing loss (SNHL) is one of the most common congenital disorders in humans, afflicting one in every thousand newborns. The majority is of heritable origin and can be divided in syndromic and nonsyndromic forms. Knowledge of the expression profile of affected genes in the human fetal cochlea is limited, and as many of the gene mutations causing SNHL likely affect the stria vascularis or cochlear potassium homeostasis (both essential to hearing), a better insight into the embryological development of this organ is needed to understand SNHL etiologies. We present an investigation on the development of the stria vascularis in the human fetal cochlea between 9 and 18 weeks of gestation (W9–W18) and show the cochlear expression dynamics of key potassium‐regulating proteins. At W12, MITF+/SOX10+/KIT+ neural‐crest‐derived melanocytes migrated into the cochlea and penetrated the basement membrane of the lateral wall epithelium, developing into the intermediate cells of the stria vascularis. These melanocytes tightly integrated with Na+/K+‐ATPase‐positive marginal cells, which started to express KCNQ1 in their apical membrane at W16. At W18, KCNJ10 and gap junction proteins GJB2/CX26 and GJB6/CX30 were expressed in the cells in the outer sulcus, but not in the spiral ligament. Finally, we investigated GJA1/CX43 and GJE1/CX23 expression, and suggest that GJE1 presents a potential new SNHL associated locus. Our study helps to better understand human cochlear development, provides more insight into multiple forms of hereditary SNHL, and suggests that human hearing does not commence before the third trimester of pregnancy. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 1219–1240, 2015

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development of the stria vascularis and potassium regulation in the human fetal cochlea: Insights into hereditary sensorineural hearing loss

Locher

Groot

Iperen

et al. 2015

Developmental Neurobiology

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“…Null mutant kcne1 mice that lack the I Ks current represent a model for the human Jervell and Lange-Nielsen syndrome that is characterized by cardiac and auditory defects (8)(9)(10). In addition to the heart and inner ear, KCNE1 also is expressed in several epithelial tissues (27,28) where its functional role is still not clearly understood (29).…”

Section: Discussionmentioning

confidence: 99%

“…RomanoWard syndrome consists only in cardiac defects. Conversely, recessive and rarer Jervell and Lange-Nielsen (JLN) syndrome comprises bilateral deafness in addition to the cardiac phenotype (8). Null mutant mice with a targeted disruption of the kcne1 gene have been engineered (9).…”

mentioning

confidence: 99%

Altered potassium balance and aldosterone secretion in a mouse model of human congenital long QT syndrome

Arrighi

Bloch-Faure²,

Grahammer³

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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The voltage-dependent K ؉ channel responsible for the slowly activating delayed K ؉ current IKs is composed of pore-forming KCNQ1 and regulatory KCNE1 subunits, which are mutated in familial forms of cardiac long QT syndrome. Because KCNQ1 and KCNE1 genes also are expressed in epithelial tissues, such as the kidneys and the intestine, we have investigated the adaptation of KCNE1-deficient mice to different K ؉ and Na ؉ intakes. On a normal K ؉ diet, homozygous kcne1 ؊/؊ mice exhibit signs of chronic volume depletion associated with fecal Na ؉ and K ؉ wasting and have lower plasma K ؉ concentration and higher levels of aldosterone than wild-type mice. Although plasma aldosterone can be suppressed by low K ؉ diets or stimulated by low Na ؉ diets, a high K ؉ diet provokes a tremendous increase of plasma aldosterone levels in kcne1 ؊/؊ mice as compared with wild-type mice (7.1-fold vs. 1.8-fold) despite lower plasma K ؉ in kcne1 ؊/؊ mice. This exacerbated aldosterone production in kcne1 ؊/؊ mice is accompanied by an abnormally high plasma renin concentration, which could partly explain the hyperaldosteronism. In addition, we found that KCNE1 and KCNQ1 mRNAs are expressed in the zona glomerulosa of adrenal glands where I Ks may directly participate in the control of aldosterone production by plasma K ؉ . These results, which show that KCNE1 and I Ks are involved in K ؉ homeostasis, might have important implications for patients with I Ks-related long QT syndrome, because hypokalemia is a well known risk factor for the occurrence of torsades de pointes ventricular arrhythmia. T he slowly activating delayed K ϩ current, known as I Ks , is formed by the assembly of two distinct subunits KCNQ1 and KCNE1 (formerly called KvLQT1 and IsK͞MinK, respectively; refs. 1 and 2). KCNQ1 is a pore-forming K ϩ channel protein with six transmembrane domains, whereas KCNE1 is a singletransmembrane domain protein that acts as a regulatory subunit (3, 4). In humans, mutations in the genes encoding these two subunits are associated with long QT (LQT) syndrome, a familial disorder that predisposes to a polymorphic type of ventricular arrhythmia known as torsades de pointes that may lead to syncope and sudden death (5).LQT syndrome includes two clinically specific syndromes that share similar cardiac abnormalities. The most frequent, called Romano-Ward syndrome, is autosomal dominant although some recessive cases also have been described (6, 7). RomanoWard syndrome consists only in cardiac defects. Conversely, recessive and rarer Jervell and Lange-Nielsen (JLN) syndrome comprises bilateral deafness in addition to the cardiac phenotype (8). Null mutant mice with a targeted disruption of the kcne1 gene have been engineered (9). At the homozygous state, these mice represent a relevant animal model of the JLN syndrome. As in JLN patients, kcne1-deficient mice bore bilateral deafness from birth because of the absence of K ϩ secretion into the endolymph (9). Analysis of the cardiac phenotype of these mice has highlighted the important role of the...

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“…Long QT syndrome (LQTS) is an inherited cardiac arrhythmia characterized by delayed ventricular repolarization, manifest on the ECG as QT prolongation and/or abnormal T‐wave morphology 1. It has long been recognized, even from Jervell and Lange‐Nielsen's original description, that adrenergic stimulation (precipitated by exercise or emotion) further delays ventricular repolarization, which is associated with a concomitant increased risk for ventricular arrhythmias in a genotype‐specific manner 2.…”

Section: Introductionmentioning

confidence: 99%

Cardiac Events During Competitive, Recreational, and Daily Activities in Children and Adolescents With Long QT Syndrome

Chambers

Ladouceur

Alexander

et al. 2017

JAHA

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BackgroundThe 2005 Bethesda Conference Guidelines advise patients with long QT syndrome against competitive sports. We assessed cardiac event rates during competitive and recreational sports, and daily activities among treated long QT syndrome patients.Methods and ResultsLong QT syndrome patients aged ≥4 years treated with anti‐adrenergic therapy were included. Demographics included mechanism of presentation, corrected QT interval pretreatment, symptom history, medication compliance, and administration of QT‐prolonging medications. Corrected QT interval ≥550 ms or prior cardiac arrest defined high risk. Sports were categorized by cardiovascular demand per the 2005 Bethesda Conference Guidelines. Each was classified as recreational or competitive. One hundred seventy‐two patients (90; 52% female) with median age 15.2 years (interquartile range 11.4, 19.4) were included. Evaluation was performed for family history (102; 59%), incidental finding (34; 20%), and symptoms (36; 21%). Median corrected QT interval was 474 ms (interquartile range 446, 496) and 14 patients (8%) were deemed high risk. Treatment included β‐blockers (171; 99%), implantable cardioverter‐defibrillator (27; 16%), left cardiac sympathetic denervation (7; 4%), and pacemaker (3; 2%). Sports participation was recreational (66; 38%) or competitive (106; 62%), with 92 (53%) exercising against the Bethesda Conference Guidelines. There were no cardiac events in competitive athletes and no deaths. There were 13 cardiac events in 9 previously symptomatic patients during either recreational exercise or activities of daily life.ConclusionsIn this cohort of appropriately managed children with long QT syndrome, cardiac event rates were low and occurred during recreational but not competitive activities. This study further supports the need for increased assessment of arrhythmia risk during exercise in this patient population.

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Congenital deaf-mutism, functional heart disease with prolongation of the Q-T interval, and sudden death

Cited by 1,403 publications

References 6 publications

Development of the stria vascularis and potassium regulation in the human fetal cochlea: Insights into hereditary sensorineural hearing loss

Development of the stria vascularis and potassium regulation in the human fetal cochlea: Insights into hereditary sensorineural hearing loss

Altered potassium balance and aldosterone secretion in a mouse model of human congenital long QT syndrome

Cardiac Events During Competitive, Recreational, and Daily Activities in Children and Adolescents With Long QT Syndrome

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