Jervell and Lange-Nielsen syndrome: Difference between revisions

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{{Infobox_Disease
{{CMG}}; {{AE}}  {{VKG}}
| Name          = {{PAGENAME}}
| Image          =
| Caption        =
| DiseasesDB    = 7249
| ICD10          =
| ICD9          = {{ICD9|426.82}}
| ICDO          =
| OMIM          = 220400
| MedlinePlus    =
| eMedicineSubj  =
  | eMedicineTopic =
| MeshID        = D029593
}}
{{CMG}}; {{AE}}  


{{SK}}Autosomal recessive long QT syndrome (LQTS), cardioauditory syndrome, cardioauditory syndrome of Jervell and Lange-Nielsen, deafness, congenital, and functional heart disease, Jervell and Lange-Nielsen (JLNS), surdocardiac syndrome  
{{SK}} Autosomal recessive long QT syndrome (LQTS), cardioauditory syndrome, cardioauditory syndrome of Jervell and Lange-Nielsen, deafness, congenital, and functional heart disease, Jervell and Lange-Nielsen (JLNS), surdocardiac syndrome  


== Overview ==
== Overview ==
Jervell and Lange-Nielsen syndrome is a rare [[autosomal recessive]] condition that leads to [[Sensorineural hearing loss|sensorineural deafness]], abnormal [[ventricular]] [[myocardial]] [[repolarization]] with results in [[long QT syndrome]] ([[Long QT syndrome|LQTS]]) and other [[cardiac]] events. Jervell and Lange-Nielsen syndrome is due to '''''[[KCNQ1]]''''' or '''''[[KCNE1]]''''' [[Gene mutation|gene mutations]]. The range of [[symptoms]] and severity of [[symptoms]] in Jervell and Lange-Nielsen syndrome differs from [[patient]] to [[patient]].
[[File:Autosomal recessive gene.png|alt=autosomal recessive pattern of inheritance|thumb|Jervell and Lange-Nielsen syndrome has an [[autosomal recessive]] pattern of [[inheritance]]. Picture courtesy by By en:User:Cburnett - Own work in Inkscape, CC BY-SA 3.0, <nowiki>https://commons.wikimedia.org/w/index.php?curid=1840082</nowiki>]]
Jervell and Lange-Nielsen syndrome is a rare [[autosomal recessive]] condition that leads to [[Sensorineural hearing loss|sensorineural deafness]], abnormal [[ventricular]] [[myocardial]] [[repolarization]] which results in [[long QT syndrome]] ([[Long QT syndrome|LQTS]]) and other [[cardiac]] events. Jervell and Lange-Nielsen syndrome is due to '''''[[KCNQ1]]''''' or '''''[[KCNE1]]''''' [[Gene mutation|gene mutations]]. The range of [[symptoms]] and severity of [[symptoms]] in Jervell and Lange-Nielsen syndrome differs from [[patient]] to [[patient]]. In The United States of America in order to categorise a [[condition]] as a [[rare disease]] it should affect fewer than 200,000 people. [[Rare diseases]] also called as [[Orphan disease|orphan diseases]]. [[Orphan Drug Act]] was passed on 1983 by congress for the [[rare diseases]]. Today an average of 25-30 million americans have been reported with [[rare diseases]]. The number of people with individual [[rare disease]] may be less but overall the number of people with [[rare diseases]] are large in number.  


== Historical Perspective ==
== Historical Perspective ==
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|[[Potassium]] [[Voltage-gated ion channel|voltage-gated]] channel subfamily E member 1
|[[Potassium]] [[Voltage-gated ion channel|voltage-gated]] channel subfamily E member 1
|}
|}
== Pathophysiology ==
== Pathophysiology ==
=== Physiology ===
=== Physiology ===
The normal [[physiology]] of ''[[KCNQ1]]'' and ''[[KCNE1]]'' [[genes]] can be understood as follows:<ref name="pmid20301579">{{cite journal| author=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K et al.| title=GeneReviews® | journal= | year= 1993 | volume=  | issue=  | pages=  | pmid=20301579 | doi= | pmc= | url= }}</ref>
The normal [[physiology]] of ''[[KCNQ1]]'' and ''[[KCNE1]]'' [[genes]] can be understood as follows:<ref name="pmid20301579">{{cite journal| author=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K et al.| title=GeneReviews® | journal= | year= 1993 | volume=  | issue=  | pages=  | pmid=20301579 | doi= | pmc= | url= }}</ref>
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'''''[[KCNQ1]]'''''  
'''''[[KCNQ1]]'''''  


* ''[[KCNQ1]]'' [[gene]] normally consists of 16 [[Exon|exons]] and have a general spanning of 400 kb.<ref name="pmid12051962">{{cite journal| author=Wang Z, Li H, Moss AJ, Robinson J, Zareba W, Knilans T et al.| title=Compound heterozygous mutations in KvLQT1 cause Jervell and Lange-Nielsen syndrome. | journal=Mol Genet Metab | year= 2002 | volume= 75 | issue= 4 | pages= 308-16 | pmid=12051962 | doi=10.1016/S1096-7192(02)00007-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12051962  }}</ref><ref name="pmid17993327">{{cite journal| author=Abbott GW, Xu X, Roepke TK| title=Impact of ancillary subunits on ventricular repolarization. | journal=J Electrocardiol | year= 2007 | volume= 40 | issue= 6 Suppl | pages= S42-6 | pmid=17993327 | doi=10.1016/j.jelectrocard.2007.05.021 | pmc=2128763 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17993327  }}</ref><ref name="pmid11874988">{{cite journal| author=Abbott GW, Goldstein SA| title=Disease-associated mutations in KCNE potassium channel subunits (MiRPs) reveal promiscuous disruption of multiple currents and conservation of mechanism. | journal=FASEB J | year= 2002 | volume= 16 | issue= 3 | pages= 390-400 | pmid=11874988 | doi=10.1096/fj.01-0520hyp | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11874988  }}</ref><ref name="pmid28595573">{{cite journal| author=Nishimura M, Ueda M, Ebata R, Utsuno E, Ishii T, Matsushita K et al.| title=A novel KCNQ1 nonsense variant in the isoform-specific first exon causes both jervell and Lange-Nielsen syndrome 1 and long QT syndrome 1: a case report. | journal=BMC Med Genet | year= 2017 | volume= 18 | issue= 1 | pages= 66 | pmid=28595573 | doi=10.1186/s12881-017-0430-7 | pmc=5465588 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28595573  }}</ref>
* ''[[KCNQ1]]'' [[gene]] normally consists of 16 [[Exon|exons]] and have a general spanning of 400 kb.<ref name="pmid12051962">{{cite journal| author=Wang Z, Li H, Moss AJ, Robinson J, Zareba W, Knilans T et al.| title=Compound heterozygous mutations in KvLQT1 cause Jervell and Lange-Nielsen syndrome. | journal=Mol Genet Metab | year= 2002 | volume= 75 | issue= 4 | pages= 308-16 | pmid=12051962 | doi=10.1016/S1096-7192(02)00007-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12051962  }}</ref><ref name="pmid17993327">{{cite journal| author=Abbott GW, Xu X, Roepke TK| title=Impact of ancillary subunits on ventricular repolarization. | journal=J Electrocardiol | year= 2007 | volume= 40 | issue= 6 Suppl | pages= S42-6 | pmid=17993327 | doi=10.1016/j.jelectrocard.2007.05.021 | pmc=2128763 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17993327  }}</ref><ref name="pmid11874988">{{cite journal| author=Abbott GW, Goldstein SA| title=Disease-associated mutations in KCNE potassium channel subunits (MiRPs) reveal promiscuous disruption of multiple currents and conservation of mechanism. | journal=FASEB J | year= 2002 | volume= 16 | issue= 3 | pages= 390-400 | pmid=11874988 | doi=10.1096/fj.01-0520hyp | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11874988  }}</ref><ref name="pmid28595573">{{cite journal| author=Nishimura M, Ueda M, Ebata R, Utsuno E, Ishii T, Matsushita K et al.| title=A novel KCNQ1 nonsense variant in the isoform-specific first exon causes both jervell and Lange-Nielsen syndrome 1 and long QT syndrome 1: a case report. | journal=BMC Med Genet | year= 2017 | volume= 18 | issue= 1 | pages= 66 | pmid=28595573 | doi=10.1186/s12881-017-0430-7 | pmc=5465588 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28595573 }}</ref><ref name="pmid90208462">{{cite journal| author=Neyroud N, Tesson F, Denjoy I, Leibovici M, Donger C, Barhanin J et al.| title=A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome. | journal=Nat Genet | year= 1997 | volume= 15 | issue= 2 | pages= 186-9 | pmid=9020846 | doi=10.1038/ng0297-186 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9020846  }}</ref><ref name="pmid17091796">{{cite journal| author=Márquez MF, Ramos-Kuri M, Hernández-Pacheco G, Estrada J, Fabregat JR, Pérez-Vielma N et al.| title=[KCNQ 1 (KvLQT1) missense mutation causing congenital long QT syndrome (Jervell-Lange-Nielsen) in a Mexican family]. | journal=Arch Cardiol Mex | year= 2006 | volume= 76 | issue= 3 | pages= 257-62 | pmid=17091796 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17091796 }}</ref>
*The normal [[gene]] product of ''[[KvLQT1|KCNQ1]]'' gene is [[potassium]] [[voltage-gated]] channel subfamily KQT member 1.
*The normal [[gene]] product of ''[[KvLQT1|KCNQ1]]'' [[gene]] is [[potassium]] [[voltage-gated]] channel subfamily KQT member 1.
* When ''[[KCNQ1]]'' gene undergoes [[frameshift mutation]] it results in yielding truncated [[protein]].
* When ''[[KCNQ1]]'' [[gene]] undergoes [[frameshift mutation]] it results in yielding truncated [[protein]].
* Then the truncated [[protein]] either delete or duplicate the [[Exon|exons]] of the ''[[KCNQ1]]'' gene and results in abnormal [[gene]] product which is known to result in [[long QT syndrome]].
* Then the truncated [[protein]] either delete or duplicate the [[Exon|exons]] of the ''[[KCNQ1]]'' gene and results in abnormal [[gene]] product which is known to result in [[long QT syndrome]].


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* Jervell and Lange-Nielsen syndrome (JLNS) is transmitted in a [[autosomal recessive]] pattern.<ref name="pmid9927399">{{cite journal| author=Priori SG, Napolitano C, Schwartz PJ| title=Low penetrance in the long-QT syndrome: clinical impact. | journal=Circulation | year= 1999 | volume= 99 | issue= 4 | pages= 529-33 | pmid=9927399 | doi=10.1161/01.cir.99.4.529 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9927399  }}</ref>
* Jervell and Lange-Nielsen syndrome (JLNS) is transmitted in a [[autosomal recessive]] pattern.<ref name="pmid9927399">{{cite journal| author=Priori SG, Napolitano C, Schwartz PJ| title=Low penetrance in the long-QT syndrome: clinical impact. | journal=Circulation | year= 1999 | volume= 99 | issue= 4 | pages= 529-33 | pmid=9927399 | doi=10.1161/01.cir.99.4.529 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9927399  }}</ref>
*Jervell and Lange-Nielsen syndrome appear to have low [[penetrance]].
*Jervell and Lange-Nielsen syndrome appear to have low [[penetrance]].<ref name="pmid187521423">{{cite journal| author=Berge KE, Haugaa KH, Früh A, Anfinsen OG, Gjesdal K, Siem G et al.| title=Molecular genetic analysis of long QT syndrome in Norway indicating a high prevalence of heterozygous mutation carriers. | journal=Scand J Clin Lab Invest | year= 2008 | volume= 68 | issue= 5 | pages= 362-8 | pmid=18752142 | doi=10.1080/00365510701765643 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18752142  }}</ref>


*[[Genes]] involved in the [[pathogenesis]] of Jervell and Lange-Nielsen syndrome (JLNS) include:
*[[Genes]] involved in the [[pathogenesis]] of Jervell and Lange-Nielsen syndrome (JLNS) include:
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== Differentiating Jervell and Lange-Nielsen syndrome from other Diseases ==
== Differentiating Jervell and Lange-Nielsen syndrome from other Diseases ==


* Jervell and Lange-Nielsen syndrome (JLNS)  must be differentiated from [[Romano-Ward syndrome]], [[Timothy syndrome]], [[Andersen-Tawil syndrome]], [[Brugada syndrome]], and [[Sudden infant death syndrome]] ([[Sudden infant death syndrome|SIDS]]).<ref name="pmid20301308">{{cite journal| author=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K et al.| title=GeneReviews® | journal= | year= 1993 | volume=  | issue=  | pages=  | pmid=20301308 | doi= | pmc= | url= }}</ref><ref name="pmid11710892">{{cite journal| author=Ackerman MJ, Siu BL, Sturner WQ, Tester DJ, Valdivia CR, Makielski JC et al.| title=Postmortem molecular analysis of SCN5A defects in sudden infant death syndrome. | journal=JAMA | year= 2001 | volume= 286 | issue= 18 | pages= 2264-9 | pmid=11710892 | doi=10.1001/jama.286.18.2264 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11710892  }}</ref><ref name="pmid17210839">{{cite journal| author=Arnestad M, Crotti L, Rognum TO, Insolia R, Pedrazzini M, Ferrandi C et al.| title=Prevalence of long-QT syndrome gene variants in sudden infant death syndrome. | journal=Circulation | year= 2007 | volume= 115 | issue= 3 | pages= 361-7 | pmid=17210839 | doi=10.1161/CIRCULATIONAHA.106.658021 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17210839  }}</ref><ref name="pmid11136691">{{cite journal| author=Schwartz PJ, Priori SG, Spazzolini C, Moss AJ, Vincent GM, Napolitano C et al.| title=Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias. | journal=Circulation | year= 2001 | volume= 103 | issue= 1 | pages= 89-95 | pmid=11136691 | doi=10.1161/01.cir.103.1.89 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11136691  }}</ref><ref name="pmid16012827">{{cite journal| author=Wedekind H, Bajanowski T, Friederich P, Breithardt G, Wülfing T, Siebrands C et al.| title=Sudden infant death syndrome and long QT syndrome: an epidemiological and genetic study. | journal=Int J Legal Med | year= 2006 | volume= 120 | issue= 3 | pages= 129-37 | pmid=16012827 | doi=10.1007/s00414-005-0019-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16012827  }}</ref>
* Jervell and Lange-Nielsen syndrome (JLNS)  must be differentiated from [[Romano-Ward syndrome]], [[Timothy syndrome]], [[Andersen-Tawil syndrome]], [[Brugada syndrome]], and [[Sudden infant death syndrome]] ([[Sudden infant death syndrome|SIDS]]).<ref name="pmid20301308">{{cite journal| author=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K et al.| title=GeneReviews® | journal= | year= 1993 | volume=  | issue=  | pages=  | pmid=20301308 | doi= | pmc= | url= }}</ref><ref name="pmid11710892">{{cite journal| author=Ackerman MJ, Siu BL, Sturner WQ, Tester DJ, Valdivia CR, Makielski JC et al.| title=Postmortem molecular analysis of SCN5A defects in sudden infant death syndrome. | journal=JAMA | year= 2001 | volume= 286 | issue= 18 | pages= 2264-9 | pmid=11710892 | doi=10.1001/jama.286.18.2264 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11710892  }}</ref><ref name="pmid17210839">{{cite journal| author=Arnestad M, Crotti L, Rognum TO, Insolia R, Pedrazzini M, Ferrandi C et al.| title=Prevalence of long-QT syndrome gene variants in sudden infant death syndrome. | journal=Circulation | year= 2007 | volume= 115 | issue= 3 | pages= 361-7 | pmid=17210839 | doi=10.1161/CIRCULATIONAHA.106.658021 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17210839  }}</ref><ref name="pmid11136691">{{cite journal| author=Schwartz PJ, Priori SG, Spazzolini C, Moss AJ, Vincent GM, Napolitano C et al.| title=Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias. | journal=Circulation | year= 2001 | volume= 103 | issue= 1 | pages= 89-95 | pmid=11136691 | doi=10.1161/01.cir.103.1.89 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11136691  }}</ref><ref name="pmid16012827">{{cite journal| author=Wedekind H, Bajanowski T, Friederich P, Breithardt G, Wülfing T, Siebrands C et al.| title=Sudden infant death syndrome and long QT syndrome: an epidemiological and genetic study. | journal=Int J Legal Med | year= 2006 | volume= 120 | issue= 3 | pages= 129-37 | pmid=16012827 | doi=10.1007/s00414-005-0019-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16012827 }}</ref><ref name="pmid27761167">{{cite journal| author=Juang JJ, Horie M| title=Genetics of Brugada syndrome. | journal=J Arrhythm | year= 2016 | volume= 32 | issue= 5 | pages= 418-425 | pmid=27761167 | doi=10.1016/j.joa.2016.07.012 | pmc=5063259 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27761167  }}</ref><ref name="pmid15950200">{{cite journal| author=Thomas D, Wimmer AB, Karle CA, Licka M, Alter M, Khalil M et al.| title=Dominant-negative I(Ks) suppression by KCNQ1-deltaF339 potassium channels linked to Romano-Ward syndrome. | journal=Cardiovasc Res | year= 2005 | volume= 67 | issue= 3 | pages= 487-97 | pmid=15950200 | doi=10.1016/j.cardiores.2005.05.003 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15950200 }}</ref>


== Epidemiology and Demographics ==
== Epidemiology and Demographics ==
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=== Incidence ===
=== Incidence ===


* The [[incidence]] of Jervell and Lange-Nielsen syndrome (JLNS) is approximately 1 per 100,000 individuals in Norway.
* The [[incidence]] of Jervell and Lange-Nielsen syndrome (JLNS) is approximately 1 per 100,000 individuals in Norway.<ref name="pmid18595190">{{cite journal| author=Siem G, Früh A, Leren TP, Heimdal K, Teig E, Harris S| title=Jervell and Lange-Nielsen syndrome in Norwegian children: aspects around cochlear implantation, hearing, and balance. | journal=Ear Hear | year= 2008 | volume= 29 | issue= 2 | pages= 261-9 | pmid=18595190 | doi=10.1097/aud.0b013e3181645393 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18595190  }}</ref><ref name="pmid187521422">{{cite journal| author=Berge KE, Haugaa KH, Früh A, Anfinsen OG, Gjesdal K, Siem G et al.| title=Molecular genetic analysis of long QT syndrome in Norway indicating a high prevalence of heterozygous mutation carriers. | journal=Scand J Clin Lab Invest | year= 2008 | volume= 68 | issue= 5 | pages= 362-8 | pmid=18752142 | doi=10.1080/00365510701765643 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18752142  }}</ref><ref name="pmid24552659">{{cite journal| author=Winbo A, Stattin EL, Nordin C, Diamant UB, Persson J, Jensen SM et al.| title=Phenotype, origin and estimated prevalence of a common long QT syndrome mutation: a clinical, genealogical and molecular genetics study including Swedish R518X/KCNQ1 families. | journal=BMC Cardiovasc Disord | year= 2014 | volume= 14 | issue=  | pages= 22 | pmid=24552659 | doi=10.1186/1471-2261-14-22 | pmc=3942207 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24552659  }}</ref>
*The [[Incidence (epidemiology)|incidence]] of Jervell and Lange-Nielsen syndrome (JLNS) is approximately 1 per 100,000 individuals in Sweden.
*The [[Incidence (epidemiology)|incidence]] of Jervell and Lange-Nielsen syndrome (JLNS) is approximately 1 per 100,000 individuals in Sweden.
*It is estimated that Jervell and Lange-Nielsen syndrome (JLNS) effects 166,000 to 625,000 children worldwide.
*It is estimated that Jervell and Lange-Nielsen syndrome (JLNS) affects 166,000 to 625,000 children worldwide.


=== Prevalence ===
=== Prevalence ===


* The prevalence of Jervell and Lange-Nielsen syndrome (JLNS) is approximately 1:200,000 individuals in Norway.<ref name="pmid10704188" />
* The [[prevalence]] of Jervell and Lange-Nielsen syndrome (JLNS) is approximately 1:200,000 individuals in Norway.<ref name="pmid10704188" /><ref name="pmid22539601">{{cite journal| author=Winbo A, Stattin EL, Diamant UB, Persson J, Jensen SM, Rydberg A| title=Prevalence, mutation spectrum, and cardiac phenotype of the Jervell and Lange-Nielsen syndrome in Sweden. | journal=Europace | year= 2012 | volume= 14 | issue= 12 | pages= 1799-806 | pmid=22539601 | doi=10.1093/europace/eus111 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22539601  }}</ref>


=== Age ===
=== Age ===


* The [[incidence]] of Jervell and Lange-Nielsen syndrome (JLNS)  increases with age; the [[median]] age at [[diagnosis]] is 6.8 years.<ref name="pmid28728690">{{cite journal| author=Rohatgi RK, Sugrue A, Bos JM, Cannon BC, Asirvatham SJ, Moir C et al.| title=Contemporary Outcomes in Patients With Long QT Syndrome. | journal=J Am Coll Cardiol | year= 2017 | volume= 70 | issue= 4 | pages= 453-462 | pmid=28728690 | doi=10.1016/j.jacc.2017.05.046 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28728690  }}</ref><ref name="pmid8099317">{{cite journal| author=Garson A, Dick M, Fournier A, Gillette PC, Hamilton R, Kugler JD et al.| title=The long QT syndrome in children. An international study of 287 patients. | journal=Circulation | year= 1993 | volume= 87 | issue= 6 | pages= 1866-72 | pmid=8099317 | doi=10.1161/01.cir.87.6.1866 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8099317  }}</ref>
* The [[incidence]] of Jervell and Lange-Nielsen syndrome (JLNS)  increases with [[age]]; the [[median]] age at [[diagnosis]] is 6.8 years.<ref name="pmid28728690">{{cite journal| author=Rohatgi RK, Sugrue A, Bos JM, Cannon BC, Asirvatham SJ, Moir C et al.| title=Contemporary Outcomes in Patients With Long QT Syndrome. | journal=J Am Coll Cardiol | year= 2017 | volume= 70 | issue= 4 | pages= 453-462 | pmid=28728690 | doi=10.1016/j.jacc.2017.05.046 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28728690  }}</ref><ref name="pmid8099317">{{cite journal| author=Garson A, Dick M, Fournier A, Gillette PC, Hamilton R, Kugler JD et al.| title=The long QT syndrome in children. An international study of 287 patients. | journal=Circulation | year= 1993 | volume= 87 | issue= 6 | pages= 1866-72 | pmid=8099317 | doi=10.1161/01.cir.87.6.1866 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8099317  }}</ref>
* The exact time of presentation in Jervell and Lange-Nielsen syndrome (JLNS)  is highly variable.
* The exact time of presentation in Jervell and Lange-Nielsen syndrome (JLNS)  is highly variable.


=== Gender ===
=== Gender ===


* Jervell and Lange-Nielsen syndrome (JLNS) affects men and women equally.
* Jervell and Lange-Nielsen syndrome (JLNS) affects [[men]] and women equally. But the severity of [[cardiac]] events is much more common in men.<ref name="pmid164618112">{{cite journal| author=Schwartz PJ, Spazzolini C, Crotti L, Bathen J, Amlie JP, Timothy K et al.| title=The Jervell and Lange-Nielsen syndrome: natural history, molecular basis, and clinical outcome. | journal=Circulation | year= 2006 | volume= 113 | issue= 6 | pages= 783-90 | pmid=16461811 | doi=10.1161/CIRCULATIONAHA.105.592899 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16461811  }}</ref><ref name="pmid211855012">{{cite journal| author=Goldenberg I, Horr S, Moss AJ, Lopes CM, Barsheshet A, McNitt S et al.| title=Risk for life-threatening cardiac events in patients with genotype-confirmed long-QT syndrome and normal-range corrected QT intervals. | journal=J Am Coll Cardiol | year= 2011 | volume= 57 | issue= 1 | pages= 51-9 | pmid=21185501 | doi=10.1016/j.jacc.2010.07.038 | pmc=3332533 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21185501  }}</ref>


== Risk Factors ==
== Risk Factors ==


* The most potent [[risk factor]] in the development of Jervell and Lange-Nielsen syndrome (JLNS) is ''[[KCNQ1]]'' and ''[[KCNE1]]'' [[genes]] [[Mutations|mutation]].
* The most potent [[risk factor]] in the development of Jervell and Lange-Nielsen syndrome (JLNS) is ''[[KCNQ1]]'' and ''[[KCNE1]]'' [[genes]] [[Mutations|mutation]].
*Other common [[risk factors]] in the development of Jervell and Lange-Nielsen syndrome (JLNS) symptoms include sudden [[sleep]] arousal, [[exercise]] and intense or sudden emotion which include the following:<ref name="SchwartzSpazzolini20062">{{cite journal|last1=Schwartz|first1=Peter J.|last2=Spazzolini|first2=Carla|last3=Crotti|first3=Lia|last4=Bathen|first4=Jørn|last5=Amlie|first5=Jan P.|last6=Timothy|first6=Katherine|last7=Shkolnikova|first7=Maria|last8=Berul|first8=Charles I.|last9=Bitner-Glindzicz|first9=Maria|last10=Toivonen|first10=Lauri|last11=Horie|first11=Minoru|last12=Schulze-Bahr|first12=Eric|last13=Denjoy|first13=Isabelle|title=The Jervell and Lange-Nielsen Syndrome|journal=Circulation|volume=113|issue=6|year=2006|pages=783–790|issn=0009-7322|doi=10.1161/CIRCULATIONAHA.105.592899}}</ref><ref name="pmid164618114">{{cite journal| author=Schwartz PJ, Spazzolini C, Crotti L, Bathen J, Amlie JP, Timothy K et al.| title=The Jervell and Lange-Nielsen syndrome: natural history, molecular basis, and clinical outcome. | journal=Circulation | year= 2006 | volume= 113 | issue= 6 | pages= 783-90 | pmid=16461811 | doi=10.1161/CIRCULATIONAHA.105.592899 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16461811  }}</ref>
** Competitive sports
** Amusement park rides
** Frightening movies
** Jumping into cold water


== Screening ==
== Screening ==


* According to the American College of Medical Genetics, screening for Jervell and Lange-Nielsen syndrome (JLNS) by hearing evaluation which is standard and electrocardiograms is recommended among patients with a family history.<ref name="pmid24388587">{{cite journal| author=Chang RK, Lan YT, Silka MJ, Morrow H, Kwong A, Smith-Lang J et al.| title=Genetic variants for long QT syndrome among infants and children from a statewide newborn hearing screening program cohort. | journal=J Pediatr | year= 2014 | volume= 164 | issue= 3 | pages= 590-5.e1-3 | pmid=24388587 | doi=10.1016/j.jpeds.2013.11.011 | pmc=3943925 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24388587  }}</ref><ref name="pmid29037160">{{cite journal| author=Uysal F, Turkgenc B, Toksoy G, Bostan OM, Evke E, Uyguner O et al.| title="Homozygous, and compound heterozygous mutation in 3 Turkish family with Jervell and Lange-Nielsen syndrome: case reports". | journal=BMC Med Genet | year= 2017 | volume= 18 | issue= 1 | pages= 114 | pmid=29037160 | doi=10.1186/s12881-017-0474-8 | pmc=5644177 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29037160  }}</ref><ref name="pmid29270100">{{cite journal| author=Olsson KS, Wålinder O, Jansson U, Wilbe M, Bondeson ML, Stattin EL et al.| title=Common founder effects of hereditary hemochromatosis, Wilson´s disease, the long QT syndrome and autosomal recessive deafness caused by two novel mutations in the WHRN and TMC1 genes. | journal=Hereditas | year= 2017 | volume= 154 | issue=  | pages= 16 | pmid=29270100 | doi=10.1186/s41065-017-0052-2 | pmc=5735936 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29270100  }}</ref>
* According to the American College of Medical Genetics, [[Screening (medicine)|screening]] for Jervell and Lange-Nielsen syndrome (JLNS) by [[hearing]] evaluation which is standard and [[electrocardiograms]] is recommended among patients with a [[family history]].<ref name="pmid24388587">{{cite journal| author=Chang RK, Lan YT, Silka MJ, Morrow H, Kwong A, Smith-Lang J et al.| title=Genetic variants for long QT syndrome among infants and children from a statewide newborn hearing screening program cohort. | journal=J Pediatr | year= 2014 | volume= 164 | issue= 3 | pages= 590-5.e1-3 | pmid=24388587 | doi=10.1016/j.jpeds.2013.11.011 | pmc=3943925 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24388587 }}</ref><ref name="pmid18752142">{{cite journal| author=Berge KE, Haugaa KH, Früh A, Anfinsen OG, Gjesdal K, Siem G et al.| title=Molecular genetic analysis of long QT syndrome in Norway indicating a high prevalence of heterozygous mutation carriers. | journal=Scand J Clin Lab Invest | year= 2008 | volume= 68 | issue= 5 | pages= 362-8 | pmid=18752142 | doi=10.1080/00365510701765643 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18752142 }}</ref><ref name="pmid29037160">{{cite journal| author=Uysal F, Turkgenc B, Toksoy G, Bostan OM, Evke E, Uyguner O et al.| title="Homozygous, and compound heterozygous mutation in 3 Turkish family with Jervell and Lange-Nielsen syndrome: case reports". | journal=BMC Med Genet | year= 2017 | volume= 18 | issue= 1 | pages= 114 | pmid=29037160 | doi=10.1186/s12881-017-0474-8 | pmc=5644177 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29037160  }}</ref><ref name="pmid29270100">{{cite journal| author=Olsson KS, Wålinder O, Jansson U, Wilbe M, Bondeson ML, Stattin EL et al.| title=Common founder effects of hereditary hemochromatosis, Wilson´s disease, the long QT syndrome and autosomal recessive deafness caused by two novel mutations in the WHRN and TMC1 genes. | journal=Hereditas | year= 2017 | volume= 154 | issue=  | pages= 16 | pmid=29270100 | doi=10.1186/s41065-017-0052-2 | pmc=5735936 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29270100  }}</ref>


== Natural History, Complications and Prognosis ==
== Natural History, Complications and Prognosis ==
Line 129: Line 117:
=== Natural History ===
=== Natural History ===


* The symptoms of Jervell and Lange-Nielsen syndrome (JLNS) usually develop in the first or second of life, and start with [[symptoms]] such as [[hearing loss]] and [[syncope]].
* The [[Symptom|symptoms]] of Jervell and Lange-Nielsen syndrome (JLNS) usually develop in the first or second of life, and start with [[symptoms]] such as [[hearing loss]] and [[syncope]].<ref name="pmid90208463">{{cite journal| author=Neyroud N, Tesson F, Denjoy I, Leibovici M, Donger C, Barhanin J et al.| title=A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome. | journal=Nat Genet | year= 1997 | volume= 15 | issue= 2 | pages= 186-9 | pmid=9020846 | doi=10.1038/ng0297-186 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9020846  }}</ref>
* The symptoms of (disease name) typically develop ___ years after exposure to ___.
* If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].


=== Complications ===
=== Complications ===


* Common complications of Jervell and Lange-Nielsen syndrome (JLNS) include:
* Common [[complications]] of Jervell and Lange-Nielsen syndrome (JLNS) include:<ref name="pmid203015795">{{cite journal| author=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K et al.| title=GeneReviews® | journal= | year= 1993 | volume=  | issue=  | pages=  | pmid=20301579 | doi= | pmc= | url= }}</ref>
** Cardiac arrhythmias
**[[Cardiac arrhythmias]]
** Seizures
**[[Seizures]]
** Sudden cardiac death
**[[Sudden cardiac death]]


=== Prognosis ===
=== Prognosis ===


* Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [--]%.
* Depending on the severity of the [[genetic]] [[mutation]] at the time of [[diagnosis]], the [[prognosis]] may vary. However, the [[prognosis]] is generally regarded as poor as most of the untreated patients die around the [[age]] of 15 years.<ref name="pmid203015792">{{cite journal| author=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K et al.| title=GeneReviews® | journal= | year= 1993 | volume=  | issue=  | pages=  | pmid=20301579 | doi= | pmc= | url= }}</ref>
* Depending on the severity of the [[genetic]] [[mutation]] at the time of [[diagnosis]], the [[prognosis]] may vary. However, the [[prognosis]] is generally regarded as poor as most of the untreated patients die around the age of 15 years.<ref name="pmid203015792">{{cite journal| author=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K et al.| title=GeneReviews® | journal= | year= 1993 | volume=  | issue=  | pages=  | pmid=20301579 | doi= | pmc= | url= }}</ref>
*The [[prognosis]] varies with the gender, [[gene mutation]] and baseline [[QT interval|QTc]] interval.
*The [[prognosis]] varies with the gender, gene mutation and baseline QTc.
* The presence of [characteristic of disease] is associated with a particularly [good/poor] prognosis among patients with [disease/malignancy].
* [Subtype of disease/malignancy] is associated with the most favorable prognosis.


== Diagnosis ==
== Diagnosis ==
==== Diagnostic Study of Choice ====
*[[Molecular]] [[genetic testing]] is the [[Gold standard (test)|gold standard]] test for the [[diagnosis]] of Jervell and Lange-Nielsen syndrome (JLNS) which includes single-[[gene]] testing, use of a multigene testing panel, and more comprehensive [[genomic]] [[testing]].<ref name="pmid203015796">{{cite journal| author=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K et al.| title=GeneReviews® | journal= | year= 1993 | volume=  | issue=  | pages=  | pmid=20301579 | doi= | pmc= | url= }}</ref>
* The following result of [[molecular]] [[genetic testing]] is confirmatory of Jervell and Lange-Nielsen syndrome (JLNS):
**''[[KCNQ1]]'' or ''[[KCNE1]]'' [[pathogenic]] [[gene mutation]] variants identification
== History and Symptoms ==
=== Common Symptoms ===
[[File:ECG recording showing prolonged QTc interval..gif|thumb|ECG recording showing prolonged QTc interval. Case courtesy by Senthil Vadivu Arumugam Et Al<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4434209/|title=Syndromic deafness-prevalence, distribution and hearing management protocol in Indian scenario|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref>]]
Common [[symptoms]] of Jervell and Lange-Nielsen syndrome (JLNS) include:
*[[Congenital]] [[Deafness]]: Usually identified at the time of birth, most commonly [[sensorineural hearing loss]] and is due to disruption of [[endolymph]] [[homeostasis]] in the cochlea and vestibular system<ref name="pmid25471708">{{cite journal| author=Winbo A, Rydberg A| title=Vestibular dysfunction is a clinical feature of the Jervell and Lange-Nielsen Syndrome. | journal=Scand Cardiovasc J | year= 2015 | volume= 49 | issue= 1 | pages= 7-13 | pmid=25471708 | doi=10.3109/14017431.2014.988172 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25471708  }}</ref>
*[[Syncope]]: Due to abnormal [[heart rhythm]] and is typically precipitous and without warning
*[[Seizures]]: Most commonly [[grand mal seizures]]
*[[Palpitations]]
*Mild to moderate [[chest pain]]
*[[Ventricular fibrillation]]
*[[Sudden cardiac death]]
== Physical Examination ==
=== HEENT ===
* All patients with Jervell and Lange-Nielsen syndrome (JLNS) are positive for profound bilateral [[congenital]] [[sensorineural deafness]].<ref name="pmid23422312">{{cite journal| author=Yamasoba T, Lin FR, Someya S, Kashio A, Sakamoto T, Kondo K| title=Current concepts in age-related hearing loss: epidemiology and mechanistic pathways. | journal=Hear Res | year= 2013 | volume= 303 | issue=  | pages= 30-8 | pmid=23422312 | doi=10.1016/j.heares.2013.01.021 | pmc=3723756 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23422312  }}</ref><ref name="pmid90208464">{{cite journal| author=Neyroud N, Tesson F, Denjoy I, Leibovici M, Donger C, Barhanin J et al.| title=A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome. | journal=Nat Genet | year= 1997 | volume= 15 | issue= 2 | pages= 186-9 | pmid=9020846 | doi=10.1038/ng0297-186 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9020846  }}</ref>
{| class="wikitable"
|+
!Hearing Loss '''Severity'''
!''' Hearing Threshold'''
|-
|Mild hearing loss
|26-40 Decibels
|-
|Moderate hearing loss
|41-55 Decibels
|-
|Moderately severe hearing loss
|56-70 Decibels
|-
|Severe hearing loss
|71-90 Decibels
|-
|Profound hearing loss
|90 Decibels
|}
=== Heart ===
[[File:Electrocardiograms (ECG) from members of a family with LQTS.gif|alt=LQTS|thumb|Representative electrocardiograms (ECG) from members of a family with LQTS. Top, ECG from a normal family member (I-1); Middle, ECG from a heterozygous mutation carrier; Bottom, ECG from a homozygous mutation carrier.<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2322962/|title=Identification of a novel KCNQ1 mutation associated with both Jervell and Lange-Nielsen and Romano-Ward forms of long QT syndrome in a Chinese family|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref>]]
*[[Cardiovascular]] examination of patients with Jervell and Lange-Nielsen syndrome (JLNS) shows '''Long [[QT interval|QTc]].'''<ref name="pmid225396012">{{cite journal| author=Winbo A, Stattin EL, Diamant UB, Persson J, Jensen SM, Rydberg A| title=Prevalence, mutation spectrum, and cardiac phenotype of the Jervell and Lange-Nielsen syndrome in Sweden. | journal=Europace | year= 2012 | volume= 14 | issue= 12 | pages= 1799-806 | pmid=22539601 | doi=10.1093/europace/eus111 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22539601  }}</ref><ref name="pmid245526592">{{cite journal| author=Winbo A, Stattin EL, Nordin C, Diamant UB, Persson J, Jensen SM et al.| title=Phenotype, origin and estimated prevalence of a common long QT syndrome mutation: a clinical, genealogical and molecular genetics study including Swedish R518X/KCNQ1 families. | journal=BMC Cardiovasc Disord | year= 2014 | volume= 14 | issue=  | pages= 22 | pmid=24552659 | doi=10.1186/1471-2261-14-22 | pmc=3942207 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24552659  }}</ref><ref name="pmid9020846">{{cite journal| author=Neyroud N, Tesson F, Denjoy I, Leibovici M, Donger C, Barhanin J et al.| title=A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome. | journal=Nat Genet | year= 1997 | volume= 15 | issue= 2 | pages= 186-9 | pmid=9020846 | doi=10.1038/ng0297-186 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9020846  }}</ref>
*Patients with Jervell and Lange-Nielsen syndrome (JLNS) shows [[QTc interval]] more than 500 mse.
*[[Palpitation|Palpitations]]
== Laboratory Findings ==
Laboratory findings consistent with the [[diagnosis]] of Jervell and Lange-Nielsen syndrome (JLNS) include:<ref name="pmid22805636">{{cite journal| author=Winbo A, Sandström O, Palmqvist R, Rydberg A| title=Iron-deficiency anaemia, gastric hyperplasia, and elevated gastrin levels due to potassium channel dysfunction in the Jervell and Lange-Nielsen Syndrome. | journal=Cardiol Young | year= 2013 | volume= 23 | issue= 3 | pages= 325-34 | pmid=22805636 | doi=10.1017/S1047951112001060 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22805636  }}</ref><ref name="pmid21118729">{{cite journal| author=Rice KS, Dickson G, Lane M, Crawford J, Chung SK, Rees MI et al.| title=Elevated serum gastrin levels in Jervell and Lange-Nielsen syndrome: a marker of severe KCNQ1 dysfunction? | journal=Heart Rhythm | year= 2011 | volume= 8 | issue= 4 | pages= 551-4 | pmid=21118729 | doi=10.1016/j.hrthm.2010.11.039 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21118729  }}</ref><ref name="pmid25127743">{{cite journal| author=Salsbury G, Cambridge EL, McIntyre Z, Arends MJ, Karp NA, Isherwood C et al.| title=Disruption of the potassium channel regulatory subunit KCNE2 causes iron-deficient anemia. | journal=Exp Hematol | year= 2014 | volume= 42 | issue= 12 | pages= 1053-8.e1 | pmid=25127743 | doi=10.1016/j.exphem.2014.07.269 | pmc=4271779 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25127743  }}</ref><ref name="pmid16754665">{{cite journal| author=Roepke TK, Anantharam A, Kirchhoff P, Busque SM, Young JB, Geibel JP et al.| title=The KCNE2 potassium channel ancillary subunit is essential for gastric acid secretion. | journal=J Biol Chem | year= 2006 | volume= 281 | issue= 33 | pages= 23740-7 | pmid=16754665 | doi=10.1074/jbc.M604155200 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16754665  }}</ref>
*[[Anemia]]: patients with Jervell and Lange-Nielsen syndrome (JLNS) are more prone to develop [[anemia]] especially [[iron deficiency anemia]]
* Hypergastrinemia is due to the [[potassium]] channels defect
*Increased [[gastrin]] levels due to gastric [[hyperplasia]]
== Electrocardiogram ==
[[File:ECG in Jervell and Lange-Nielsen syndrome.gif|thumb|ECG in Jervell and Lange-Nielsen syndrome shows markedly prolonged corrected QT interval (QTc). Case courtesy by Jae Suk Baek et al<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946666/|title=Jervell and Lange-Nielsen Syndrome: Novel Compound Heterozygous Mutations in the KCNQ1 in a Korean Family|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref>]]
An [[The electrocardiogram|ECG]] may be helpful in the [[diagnosis]] of Jervell and Lange-Nielsen syndrome (JLNS). Findings on an [[The electrocardiogram|ECG]] [[diagnostic]] of Jervell and Lange-Nielsen syndrome (JLNS) include the following:<ref name="pmid16461811" /><ref name="pmid169115783">{{cite journal| author=Goldenberg I, Moss AJ, Zareba W, McNitt S, Robinson JL, Qi M et al.| title=Clinical course and risk stratification of patients affected with the Jervell and Lange-Nielsen syndrome. | journal=J Cardiovasc Electrophysiol | year= 2006 | volume= 17 | issue= 11 | pages= 1161-8 | pmid=16911578 | doi=10.1111/j.1540-8167.2006.00587.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16911578  }}</ref><ref name="pmid21185501">{{cite journal| author=Goldenberg I, Horr S, Moss AJ, Lopes CM, Barsheshet A, McNitt S et al.| title=Risk for life-threatening cardiac events in patients with genotype-confirmed long-QT syndrome and normal-range corrected QT intervals. | journal=J Am Coll Cardiol | year= 2011 | volume= 57 | issue= 1 | pages= 51-9 | pmid=21185501 | doi=10.1016/j.jacc.2010.07.038 | pmc=3332533 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21185501  }}</ref>
* Prolongation of the [[QTc interval]] greater than 500 msec
*[[Tachyarrhythmias]]: due to abnormal [[cardiac]] [[depolarization]] and [[cardiac]] [[repolarization]]
*[[Ventricular tachycardia]]
*[[Torsade de pointes]] ventricular [[tachycardia]]
*[[Ventricular fibrillation]]
Stress [[The electrocardiogram|ECG]] or a [[Treadmill test|treadmill]] [[The electrocardiogram|ECG]] Testing also may be helpful in the [[diagnosis]] of Jervell and Lange-Nielsen syndrome (JLNS)
== Imaging Findings ==
There are no other imaging findings associated with Jervell and Lange-Nielsen syndrome (JLNS).


== Treatment ==
== Treatment ==
=== Medical Therapy ===
*[[Patient|Patients]] with Jervell and Lange-Nielsen syndrome (JLNS) are treated with [[beta-adrenergic]] blockers as the first line in the management of the [[disease]].
*In [[Patient|patients]] with Jervell and Lange-Nielsen syndrome (JLNS) despite treated with the [[Beta blockers|beta-blockers]] risk of [[cardiac]] events still persists.<ref name="pmid19118258">{{cite journal| author=Vincent GM, Schwartz PJ, Denjoy I, Swan H, Bithell C, Spazzolini C et al.| title=High efficacy of beta-blockers in long-QT syndrome type 1: contribution of noncompliance and QT-prolonging drugs to the occurrence of beta-blocker treatment "failures". | journal=Circulation | year= 2009 | volume= 119 | issue= 2 | pages= 215-21 | pmid=19118258 | doi=10.1161/CIRCULATIONAHA.108.772533 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19118258  }}</ref><ref name="pmid16911578">{{cite journal| author=Goldenberg I, Moss AJ, Zareba W, McNitt S, Robinson JL, Qi M et al.| title=Clinical course and risk stratification of patients affected with the Jervell and Lange-Nielsen syndrome. | journal=J Cardiovasc Electrophysiol | year= 2006 | volume= 17 | issue= 11 | pages= 1161-8 | pmid=16911578 | doi=10.1111/j.1540-8167.2006.00587.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16911578  }}</ref>
*[[Propranolol]] and [[Nadolol (tablet)|nadolol]] are the [[beta-blockers]] of choice when treating a patient with Jervell and Lange-Nielsen syndrome (JLNS). Of the two [[Nadolol (tablet)|nadolol]] is the preference of choice due to less favorable [[Pharmacokinetics|pharmacokinetic]] profile of [[propranolol]].<ref name="pmid164618113">{{cite journal| author=Schwartz PJ, Spazzolini C, Crotti L, Bathen J, Amlie JP, Timothy K et al.| title=The Jervell and Lange-Nielsen syndrome: natural history, molecular basis, and clinical outcome. | journal=Circulation | year= 2006 | volume= 113 | issue= 6 | pages= 783-90 | pmid=16461811 | doi=10.1161/CIRCULATIONAHA.105.592899 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16461811  }}</ref>
**<nowiki/> Preferred regimen (1): [[Nadolol]]  1–1.5 mg/kg/day administered once a day in patients ≥12 years of age, divided twice daily in [[Infant|infants]] and [[children]]
'''Acute Management of Torsades de pointes'''
* The treatment of choice for [[Hemodynamically unstable|hemodynamically]] unstable patients [[Acute (medicine)|acute]] management of [[Torsades de pointes]] in Jervell and Lange-Nielsen syndrome (JLNS) patients are with the following:<ref name="pmid203015794">{{cite journal| author=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K et al.| title=GeneReviews® | journal= | year= 1993 | volume=  | issue=  | pages=  | pmid=20301579 | doi= | pmc= | url= }}</ref><ref name="pmid169115782">{{cite journal| author=Goldenberg I, Moss AJ, Zareba W, McNitt S, Robinson JL, Qi M et al.| title=Clinical course and risk stratification of patients affected with the Jervell and Lange-Nielsen syndrome. | journal=J Cardiovasc Electrophysiol | year= 2006 | volume= 17 | issue= 11 | pages= 1161-8 | pmid=16911578 | doi=10.1111/j.1540-8167.2006.00587.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16911578  }}</ref>
** Electrical [[cardioversion]] or [[defibrillation]]
** If [[ventricular tachycardia]] is suspected or diagnosed treat the patient with [[cardiopulmonary]] [[resuscitation]] and the [[advanced cardiac life support]] ([[Advanced cardiac life support|ACLS]]) protocol has to be initiated.
*If the patient is [[hemodynamically]] stable or [[cardioversion]] fails then treat the patient with following:
**Preferred regimen (1): [[Magnesium sulfate]] 20–50 mg/kg [[Intravenous therapy|intravenously]] initially up to 2 grams max.
== Interventions ==
* The feasibility of interventions depends on the severity of Jervell and Lange-Nielsen syndrome (JLNS) patients at the time of [[diagnosis]] which include:
**[[Implantable cardioverter defibrillator|Implantable cardioverter-defibrillators]] ([[ICD|ICDs]])<ref name="pmid15028076">{{cite journal| author=Alexander ME, Cecchin F, Walsh EP, Triedman JK, Bevilacqua LM, Berul CI| title=Implications of implantable cardioverter defibrillator therapy in congenital heart disease and pediatrics. | journal=J Cardiovasc Electrophysiol | year= 2004 | volume= 15 | issue= 1 | pages= 72-6 | pmid=15028076 | doi=10.1046/j.1540-8167.2004.03388.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15028076  }}</ref><ref name="pmid20170817">{{cite journal| author=Jons C, Moss AJ, Goldenberg I, Liu J, McNitt S, Zareba W et al.| title=Risk of fatal arrhythmic events in long QT syndrome patients after syncope. | journal=J Am Coll Cardiol | year= 2010 | volume= 55 | issue= 8 | pages= 783-8 | pmid=20170817 | doi=10.1016/j.jacc.2009.11.042 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20170817  }}</ref><ref name="pmid169115784">{{cite journal| author=Goldenberg I, Moss AJ, Zareba W, McNitt S, Robinson JL, Qi M et al.| title=Clinical course and risk stratification of patients affected with the Jervell and Lange-Nielsen syndrome. | journal=J Cardiovasc Electrophysiol | year= 2006 | volume= 17 | issue= 11 | pages= 1161-8 | pmid=16911578 | doi=10.1111/j.1540-8167.2006.00587.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16911578  }}</ref>
***[[Implantable cardioverter defibrillator|ICDs]] are reserved for the patients who undergone [[cardiac arrest]] [[resuscitation]]
***[[Implantable cardioverter defibrillator|ICDs]] are good alternative choice of treatment for the patients who are resistant to [[beta blockers]]
** Left [[cardiac]] [[sympathetic]] denervation (LCSD)
***LCSDs are reserved for the patients who are not compatible with [[Beta blockers|beta blocker]] or [[Implantable cardioverter defibrillator|Implantable cardioverter-defibrillators]] ([[Implantable cardioverter defibrillator|ICDs]])
== Surgery ==
* Surgical [[Intervention (counseling)|intervention]] is not the first line for the management of Jervell and Lange-Nielsen syndrome (JLNS). But it is recommended for the patients who are having [[Hearing (sense)|hearing]] problem which includes the following:<ref name="pmid17498328">{{cite journal| author=Daneshi A, Ghassemi MM, Talee M, Hassanzadeh S| title=Cochlear implantation in children with Jervell, Lange-Nielsen syndrome. | journal=J Laryngol Otol | year= 2008 | volume= 122 | issue= 3 | pages= 314-7 | pmid=17498328 | doi=10.1017/S0022215107007712 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17498328  }}</ref><ref name="pmid185951902">{{cite journal| author=Siem G, Früh A, Leren TP, Heimdal K, Teig E, Harris S| title=Jervell and Lange-Nielsen syndrome in Norwegian children: aspects around cochlear implantation, hearing, and balance. | journal=Ear Hear | year= 2008 | volume= 29 | issue= 2 | pages= 261-9 | pmid=18595190 | doi=10.1097/aud.0b013e3181645393 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18595190  }}</ref><ref name="pmid18805595">{{cite journal| author=Yanmei F, Yaqin W, Haibo S, Huiqun Z, Zhengnong C, Dongzhen Y et al.| title=Cochlear implantation in patients with Jervell and Lange-Nielsen syndrome, and a review of literature. | journal=Int J Pediatr Otorhinolaryngol | year= 2008 | volume= 72 | issue= 11 | pages= 1723-9 | pmid=18805595 | doi=10.1016/j.ijporl.2008.07.013 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18805595  }}</ref>
**[[Cochlear nerve|Cochlear]] [[implantation]]: Which is safe and improves the quality of life
== Primary Prevention ==
* There are no established measures for the [[primary prevention]] of Jervell and Lange-Nielsen syndrome (JLNS).
== Secondary Prevention ==
* Effective measures for the [[secondary prevention]] of Jervell and Lange-Nielsen syndrome (JLNS) include:<ref name="pmid203015793">{{cite journal| author=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K et al.| title=GeneReviews® | journal= | year= 1993 | volume=  | issue=  | pages=  | pmid=20301579 | doi= | pmc= | url= }}</ref>
** Taking special care while giving the [[anesthesia]] due to the risk of [[cardiac]] [[arrhythmias]]
** Avoiding intense or sudden emotions which are trigger for [[syncope]]
[[Category:Electrophysiology]]
[[Category:Electrophysiology]]
[[Category:Genetic disorders]]
[[Category:Genetic disorders]]
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[[fr:Syndrome de Jervell et Lange-Nielsen]]
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[[pl:Zespół Jervella i Lange-Nielsena]]
[[tr:Jervel-Lange-Nielsen syndrome]]
[[tr:Jervell-Lange-Nielsen syndrome]]
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Latest revision as of 15:29, 24 January 2020

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vamsikrishna Gunnam M.B.B.S [2]

Synonyms and keywords: Autosomal recessive long QT syndrome (LQTS), cardioauditory syndrome, cardioauditory syndrome of Jervell and Lange-Nielsen, deafness, congenital, and functional heart disease, Jervell and Lange-Nielsen (JLNS), surdocardiac syndrome

Overview

autosomal recessive pattern of inheritance
Jervell and Lange-Nielsen syndrome has an autosomal recessive pattern of inheritance. Picture courtesy by By en:User:Cburnett - Own work in Inkscape, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=1840082

Jervell and Lange-Nielsen syndrome is a rare autosomal recessive condition that leads to sensorineural deafness, abnormal ventricular myocardial repolarization which results in long QT syndrome (LQTS) and other cardiac events. Jervell and Lange-Nielsen syndrome is due to KCNQ1 or KCNE1 gene mutations. The range of symptoms and severity of symptoms in Jervell and Lange-Nielsen syndrome differs from patient to patient. In The United States of America in order to categorise a condition as a rare disease it should affect fewer than 200,000 people. Rare diseases also called as orphan diseases. Orphan Drug Act was passed on 1983 by congress for the rare diseases. Today an average of 25-30 million americans have been reported with rare diseases. The number of people with individual rare disease may be less but overall the number of people with rare diseases are large in number.

Historical Perspective

  • Jervell and Lange-Nielsen syndrome (JLNS) was first discovered by Anton Jervell a Norwegian physician and Fred Lange-Nielsen a Norwegian doctor and jazz musician, in 1957.[1][2]

Classification

  • Jervell and Lange-Nielsen syndrome (JLNS) may be classified according into two subtypes:[3][4][5][6]
Type Chromosome Locus Gene Mutation Protein Involved
Jervell and Lange-Nielsen syndrome 1 11p15​.5-p15.4 KCNQ1 Potassium voltage-gated channel subfamily KQT member 1
Jervell and Lange-Nielsen syndrome 2 21q22​.12 KCNE1 Potassium voltage-gated channel subfamily E member 1

Pathophysiology

Physiology

The normal physiology of KCNQ1 and KCNE1 genes can be understood as follows:[7]

Pathogenesis

KCNQ1

KCNE1

Genetics

Causes

Genetic Causes

Differentiating Jervell and Lange-Nielsen syndrome from other Diseases

Epidemiology and Demographics

Incidence

  • The incidence of Jervell and Lange-Nielsen syndrome (JLNS) is approximately 1 per 100,000 individuals in Norway.[30][31][32]
  • The incidence of Jervell and Lange-Nielsen syndrome (JLNS) is approximately 1 per 100,000 individuals in Sweden.
  • It is estimated that Jervell and Lange-Nielsen syndrome (JLNS) affects 166,000 to 625,000 children worldwide.

Prevalence

  • The prevalence of Jervell and Lange-Nielsen syndrome (JLNS) is approximately 1:200,000 individuals in Norway.[1][33]

Age

  • The incidence of Jervell and Lange-Nielsen syndrome (JLNS) increases with age; the median age at diagnosis is 6.8 years.[34][35]
  • The exact time of presentation in Jervell and Lange-Nielsen syndrome (JLNS) is highly variable.

Gender

  • Jervell and Lange-Nielsen syndrome (JLNS) affects men and women equally. But the severity of cardiac events is much more common in men.[36][37]

Risk Factors

  • The most potent risk factor in the development of Jervell and Lange-Nielsen syndrome (JLNS) is KCNQ1 and KCNE1 genes mutation.
  • Other common risk factors in the development of Jervell and Lange-Nielsen syndrome (JLNS) symptoms include sudden sleep arousal, exercise and intense or sudden emotion which include the following:[38][39]
    • Competitive sports
    • Amusement park rides
    • Frightening movies
    • Jumping into cold water

Screening

Natural History, Complications and Prognosis

Natural History

Complications

Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Common Symptoms

ECG recording showing prolonged QTc interval. Case courtesy by Senthil Vadivu Arumugam Et Al[48]

Common symptoms of Jervell and Lange-Nielsen syndrome (JLNS) include:

Physical Examination

HEENT

Hearing Loss Severity Hearing Threshold
Mild hearing loss 26-40 Decibels
Moderate hearing loss 41-55 Decibels
Moderately severe hearing loss 56-70 Decibels
Severe hearing loss 71-90 Decibels
Profound hearing loss 90 Decibels

Heart

LQTS
Representative electrocardiograms (ECG) from members of a family with LQTS. Top, ECG from a normal family member (I-1); Middle, ECG from a heterozygous mutation carrier; Bottom, ECG from a homozygous mutation carrier.[52]

Laboratory Findings

Laboratory findings consistent with the diagnosis of Jervell and Lange-Nielsen syndrome (JLNS) include:[56][57][58][59]

Electrocardiogram

ECG in Jervell and Lange-Nielsen syndrome shows markedly prolonged corrected QT interval (QTc). Case courtesy by Jae Suk Baek et al[60]

An ECG may be helpful in the diagnosis of Jervell and Lange-Nielsen syndrome (JLNS). Findings on an ECG diagnostic of Jervell and Lange-Nielsen syndrome (JLNS) include the following:[4][61][62]

Stress ECG or a treadmill ECG Testing also may be helpful in the diagnosis of Jervell and Lange-Nielsen syndrome (JLNS)

Imaging Findings

There are no other imaging findings associated with Jervell and Lange-Nielsen syndrome (JLNS).

Treatment

Medical Therapy

Acute Management of Torsades de pointes

Interventions

Surgery

  • Surgical intervention is not the first line for the management of Jervell and Lange-Nielsen syndrome (JLNS). But it is recommended for the patients who are having hearing problem which includes the following:[71][72][73]

Primary Prevention

  • There are no established measures for the primary prevention of Jervell and Lange-Nielsen syndrome (JLNS).

Secondary Prevention

Template:WikiDoc Sources

References

  1. ↑ 1.0 1.1 Tranebjaerg L, Bathen J, Tyson J, Bitner-Glindzicz M (1999). "Jervell and Lange-Nielsen syndrome: a Norwegian perspective". Am J Med Genet. 89 (3): 137–46. PMID 10704188.
  2. ↑ Schwartz, Peter J.; Spazzolini, Carla; Crotti, Lia; Bathen, Jørn; Amlie, Jan P.; Timothy, Katherine; Shkolnikova, Maria; Berul, Charles I.; Bitner-Glindzicz, Maria; Toivonen, Lauri; Horie, Minoru; Schulze-Bahr, Eric; Denjoy, Isabelle (2006). "The Jervell and Lange-Nielsen Syndrome". Circulation. 113 (6): 783–790. doi:10.1161/CIRCULATIONAHA.105.592899. ISSN 0009-7322.
  3. ↑ Tyson J, Tranebjaerg L, McEntagart M, Larsen LA, Christiansen M, Whiteford ML; et al. (2000). "Mutational spectrum in the cardioauditory syndrome of Jervell and Lange-Nielsen". Hum Genet. 107 (5): 499–503. doi:10.1007/s004390000402. PMID 11140949.
  4. ↑ 4.0 4.1 Schwartz PJ, Spazzolini C, Crotti L, Bathen J, Amlie JP, Timothy K; et al. (2006). "The Jervell and Lange-Nielsen syndrome: natural history, molecular basis, and clinical outcome". Circulation. 113 (6): 783–90. doi:10.1161/CIRCULATIONAHA.105.592899. PMID 16461811.
  5. ↑ Tranebjaerg L, Bathen J, Tyson J, Bitner-Glindzicz M (1999). "Jervell and Lange-Nielsen syndrome: a Norwegian perspective". Am J Med Genet. 89 (3): 137–46. PMID 10704188.
  6. ↑ ACMG (2002) Genetics Evaluation Guidelines for the Etiologic Diagnosis of Congenital Hearing Loss. Genetic Evaluation of Congenital Hearing Loss Expert Panel. ACMG statement. Genet Med 4 (3):162-71. DOI:10.1097/00125817-200205000-00011 PMID: 12180152
  7. ↑ Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). "GeneReviews®". PMID 20301579.
  8. ↑ Tranebjaerg L, Bathen J, Tyson J, Bitner-Glindzicz M (1999). "Jervell and Lange-Nielsen syndrome: a Norwegian perspective". Am J Med Genet. 89 (3): 137–46. PMID 10704188.
  9. ↑ Wang Z, Li H, Moss AJ, Robinson J, Zareba W, Knilans T; et al. (2002). "Compound heterozygous mutations in KvLQT1 cause Jervell and Lange-Nielsen syndrome". Mol Genet Metab. 75 (4): 308–16. doi:10.1016/S1096-7192(02)00007-0. PMID 12051962.
  10. ↑ Abbott GW, Xu X, Roepke TK (2007). "Impact of ancillary subunits on ventricular repolarization". J Electrocardiol. 40 (6 Suppl): S42–6. doi:10.1016/j.jelectrocard.2007.05.021. PMC 2128763. PMID 17993327.
  11. ↑ Abbott GW, Goldstein SA (2002). "Disease-associated mutations in KCNE potassium channel subunits (MiRPs) reveal promiscuous disruption of multiple currents and conservation of mechanism". FASEB J. 16 (3): 390–400. doi:10.1096/fj.01-0520hyp. PMID 11874988.
  12. ↑ Nishimura M, Ueda M, Ebata R, Utsuno E, Ishii T, Matsushita K; et al. (2017). "A novel KCNQ1 nonsense variant in the isoform-specific first exon causes both jervell and Lange-Nielsen syndrome 1 and long QT syndrome 1: a case report". BMC Med Genet. 18 (1): 66. doi:10.1186/s12881-017-0430-7. PMC 5465588. PMID 28595573.
  13. ↑ Neyroud N, Tesson F, Denjoy I, Leibovici M, Donger C, Barhanin J; et al. (1997). "A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome". Nat Genet. 15 (2): 186–9. doi:10.1038/ng0297-186. PMID 9020846.
  14. ↑ Márquez MF, Ramos-Kuri M, Hernández-Pacheco G, Estrada J, Fabregat JR, Pérez-Vielma N; et al. (2006). "[KCNQ 1 (KvLQT1) missense mutation causing congenital long QT syndrome (Jervell-Lange-Nielsen) in a Mexican family]". Arch Cardiol Mex. 76 (3): 257–62. PMID 17091796.
  15. ↑ Lewis A, McCrossan ZA, Abbott GW (2004). "MinK, MiRP1, and MiRP2 diversify Kv3.1 and Kv3.2 potassium channel gating". J Biol Chem. 279 (9): 7884–92. doi:10.1074/jbc.M310501200. PMID 14679187.
  16. ↑ Lu Y, Mahaut-Smith MP, Huang CL, Vandenberg JI (2003). "Mutant MiRP1 subunits modulate HERG K+ channel gating: a mechanism for pro-arrhythmia in long QT syndrome type 6". J Physiol. 551 (Pt 1): 253–62. doi:10.1113/jphysiol.2003.046045. PMC 2343156. PMID 12923204.
  17. ↑ Anantharam A, Abbott GW (2005). "Does hERG coassemble with a beta subunit? Evidence for roles of MinK and MiRP1". Novartis Found Symp. 266: 100–12, discussion 112-7, 155–8. PMID 16050264.
  18. ↑ Abbott GW, Goldstein SA (2002). "Disease-associated mutations in KCNE potassium channel subunits (MiRPs) reveal promiscuous disruption of multiple currents and conservation of mechanism". FASEB J. 16 (3): 390–400. doi:10.1096/fj.01-0520hyp. PMID 11874988.
  19. ↑ Abbott GW, Xu X, Roepke TK (2007). "Impact of ancillary subunits on ventricular repolarization". J Electrocardiol. 40 (6 Suppl): S42–6. doi:10.1016/j.jelectrocard.2007.05.021. PMC 2128763. PMID 17993327.
  20. ↑ McCrossan ZA, Roepke TK, Lewis A, Panaghie G, Abbott GW (2009). "Regulation of the Kv2.1 potassium channel by MinK and MiRP1". J Membr Biol. 228 (1): 1–14. doi:10.1007/s00232-009-9154-8. PMC 2849987. PMID 19219384.
  21. ↑ Priori SG, Napolitano C, Schwartz PJ (1999). "Low penetrance in the long-QT syndrome: clinical impact". Circulation. 99 (4): 529–33. doi:10.1161/01.cir.99.4.529. PMID 9927399.
  22. ↑ Berge KE, Haugaa KH, Früh A, Anfinsen OG, Gjesdal K, Siem G; et al. (2008). "Molecular genetic analysis of long QT syndrome in Norway indicating a high prevalence of heterozygous mutation carriers". Scand J Clin Lab Invest. 68 (5): 362–8. doi:10.1080/00365510701765643. PMID 18752142.
  23. ↑ Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). "GeneReviews®". PMID 20301308.
  24. ↑ Ackerman MJ, Siu BL, Sturner WQ, Tester DJ, Valdivia CR, Makielski JC; et al. (2001). "Postmortem molecular analysis of SCN5A defects in sudden infant death syndrome". JAMA. 286 (18): 2264–9. doi:10.1001/jama.286.18.2264. PMID 11710892.
  25. ↑ Arnestad M, Crotti L, Rognum TO, Insolia R, Pedrazzini M, Ferrandi C; et al. (2007). "Prevalence of long-QT syndrome gene variants in sudden infant death syndrome". Circulation. 115 (3): 361–7. doi:10.1161/CIRCULATIONAHA.106.658021. PMID 17210839.
  26. ↑ Schwartz PJ, Priori SG, Spazzolini C, Moss AJ, Vincent GM, Napolitano C; et al. (2001). "Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias". Circulation. 103 (1): 89–95. doi:10.1161/01.cir.103.1.89. PMID 11136691.
  27. ↑ Wedekind H, Bajanowski T, Friederich P, Breithardt G, Wülfing T, Siebrands C; et al. (2006). "Sudden infant death syndrome and long QT syndrome: an epidemiological and genetic study". Int J Legal Med. 120 (3): 129–37. doi:10.1007/s00414-005-0019-0. PMID 16012827.
  28. ↑ Juang JJ, Horie M (2016). "Genetics of Brugada syndrome". J Arrhythm. 32 (5): 418–425. doi:10.1016/j.joa.2016.07.012. PMC 5063259. PMID 27761167.
  29. ↑ Thomas D, Wimmer AB, Karle CA, Licka M, Alter M, Khalil M; et al. (2005). "Dominant-negative I(Ks) suppression by KCNQ1-deltaF339 potassium channels linked to Romano-Ward syndrome". Cardiovasc Res. 67 (3): 487–97. doi:10.1016/j.cardiores.2005.05.003. PMID 15950200.
  30. ↑ Siem G, Früh A, Leren TP, Heimdal K, Teig E, Harris S (2008). "Jervell and Lange-Nielsen syndrome in Norwegian children: aspects around cochlear implantation, hearing, and balance". Ear Hear. 29 (2): 261–9. doi:10.1097/aud.0b013e3181645393. PMID 18595190.
  31. ↑ Berge KE, Haugaa KH, Früh A, Anfinsen OG, Gjesdal K, Siem G; et al. (2008). "Molecular genetic analysis of long QT syndrome in Norway indicating a high prevalence of heterozygous mutation carriers". Scand J Clin Lab Invest. 68 (5): 362–8. doi:10.1080/00365510701765643. PMID 18752142.
  32. ↑ Winbo A, Stattin EL, Nordin C, Diamant UB, Persson J, Jensen SM; et al. (2014). "Phenotype, origin and estimated prevalence of a common long QT syndrome mutation: a clinical, genealogical and molecular genetics study including Swedish R518X/KCNQ1 families". BMC Cardiovasc Disord. 14: 22. doi:10.1186/1471-2261-14-22. PMC 3942207. PMID 24552659.
  33. ↑ Winbo A, Stattin EL, Diamant UB, Persson J, Jensen SM, Rydberg A (2012). "Prevalence, mutation spectrum, and cardiac phenotype of the Jervell and Lange-Nielsen syndrome in Sweden". Europace. 14 (12): 1799–806. doi:10.1093/europace/eus111. PMID 22539601.
  34. ↑ Rohatgi RK, Sugrue A, Bos JM, Cannon BC, Asirvatham SJ, Moir C; et al. (2017). "Contemporary Outcomes in Patients With Long QT Syndrome". J Am Coll Cardiol. 70 (4): 453–462. doi:10.1016/j.jacc.2017.05.046. PMID 28728690.
  35. ↑ Garson A, Dick M, Fournier A, Gillette PC, Hamilton R, Kugler JD; et al. (1993). "The long QT syndrome in children. An international study of 287 patients". Circulation. 87 (6): 1866–72. doi:10.1161/01.cir.87.6.1866. PMID 8099317.
  36. ↑ Schwartz PJ, Spazzolini C, Crotti L, Bathen J, Amlie JP, Timothy K; et al. (2006). "The Jervell and Lange-Nielsen syndrome: natural history, molecular basis, and clinical outcome". Circulation. 113 (6): 783–90. doi:10.1161/CIRCULATIONAHA.105.592899. PMID 16461811.
  37. ↑ Goldenberg I, Horr S, Moss AJ, Lopes CM, Barsheshet A, McNitt S; et al. (2011). "Risk for life-threatening cardiac events in patients with genotype-confirmed long-QT syndrome and normal-range corrected QT intervals". J Am Coll Cardiol. 57 (1): 51–9. doi:10.1016/j.jacc.2010.07.038. PMC 3332533. PMID 21185501.
  38. ↑ Schwartz, Peter J.; Spazzolini, Carla; Crotti, Lia; Bathen, Jørn; Amlie, Jan P.; Timothy, Katherine; Shkolnikova, Maria; Berul, Charles I.; Bitner-Glindzicz, Maria; Toivonen, Lauri; Horie, Minoru; Schulze-Bahr, Eric; Denjoy, Isabelle (2006). "The Jervell and Lange-Nielsen Syndrome". Circulation. 113 (6): 783–790. doi:10.1161/CIRCULATIONAHA.105.592899. ISSN 0009-7322.
  39. ↑ Schwartz PJ, Spazzolini C, Crotti L, Bathen J, Amlie JP, Timothy K; et al. (2006). "The Jervell and Lange-Nielsen syndrome: natural history, molecular basis, and clinical outcome". Circulation. 113 (6): 783–90. doi:10.1161/CIRCULATIONAHA.105.592899. PMID 16461811.
  40. ↑ Chang RK, Lan YT, Silka MJ, Morrow H, Kwong A, Smith-Lang J; et al. (2014). "Genetic variants for long QT syndrome among infants and children from a statewide newborn hearing screening program cohort". J Pediatr. 164 (3): 590-5.e1-3. doi:10.1016/j.jpeds.2013.11.011. PMC 3943925. PMID 24388587.
  41. ↑ Berge KE, Haugaa KH, Früh A, Anfinsen OG, Gjesdal K, Siem G; et al. (2008). "Molecular genetic analysis of long QT syndrome in Norway indicating a high prevalence of heterozygous mutation carriers". Scand J Clin Lab Invest. 68 (5): 362–8. doi:10.1080/00365510701765643. PMID 18752142.
  42. ↑ Uysal F, Turkgenc B, Toksoy G, Bostan OM, Evke E, Uyguner O; et al. (2017). ""Homozygous, and compound heterozygous mutation in 3 Turkish family with Jervell and Lange-Nielsen syndrome: case reports"". BMC Med Genet. 18 (1): 114. doi:10.1186/s12881-017-0474-8. PMC 5644177. PMID 29037160.
  43. ↑ Olsson KS, Wålinder O, Jansson U, Wilbe M, Bondeson ML, Stattin EL; et al. (2017). "Common founder effects of hereditary hemochromatosis, Wilson´s disease, the long QT syndrome and autosomal recessive deafness caused by two novel mutations in the WHRN and TMC1 genes". Hereditas. 154: 16. doi:10.1186/s41065-017-0052-2. PMC 5735936. PMID 29270100.
  44. ↑ Neyroud N, Tesson F, Denjoy I, Leibovici M, Donger C, Barhanin J; et al. (1997). "A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome". Nat Genet. 15 (2): 186–9. doi:10.1038/ng0297-186. PMID 9020846.
  45. ↑ Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). "GeneReviews®". PMID 20301579.
  46. ↑ Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). "GeneReviews®". PMID 20301579.
  47. ↑ Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). "GeneReviews®". PMID 20301579.
  48. ↑ "Syndromic deafness-prevalence, distribution and hearing management protocol in Indian scenario".
  49. ↑ Winbo A, Rydberg A (2015). "Vestibular dysfunction is a clinical feature of the Jervell and Lange-Nielsen Syndrome". Scand Cardiovasc J. 49 (1): 7–13. doi:10.3109/14017431.2014.988172. PMID 25471708.
  50. ↑ Yamasoba T, Lin FR, Someya S, Kashio A, Sakamoto T, Kondo K (2013). "Current concepts in age-related hearing loss: epidemiology and mechanistic pathways". Hear Res. 303: 30–8. doi:10.1016/j.heares.2013.01.021. PMC 3723756. PMID 23422312.
  51. ↑ Neyroud N, Tesson F, Denjoy I, Leibovici M, Donger C, Barhanin J; et al. (1997). "A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome". Nat Genet. 15 (2): 186–9. doi:10.1038/ng0297-186. PMID 9020846.
  52. ↑ "Identification of a novel KCNQ1 mutation associated with both Jervell and Lange-Nielsen and Romano-Ward forms of long QT syndrome in a Chinese family".
  53. ↑ Winbo A, Stattin EL, Diamant UB, Persson J, Jensen SM, Rydberg A (2012). "Prevalence, mutation spectrum, and cardiac phenotype of the Jervell and Lange-Nielsen syndrome in Sweden". Europace. 14 (12): 1799–806. doi:10.1093/europace/eus111. PMID 22539601.
  54. ↑ Winbo A, Stattin EL, Nordin C, Diamant UB, Persson J, Jensen SM; et al. (2014). "Phenotype, origin and estimated prevalence of a common long QT syndrome mutation: a clinical, genealogical and molecular genetics study including Swedish R518X/KCNQ1 families". BMC Cardiovasc Disord. 14: 22. doi:10.1186/1471-2261-14-22. PMC 3942207. PMID 24552659.
  55. ↑ Neyroud N, Tesson F, Denjoy I, Leibovici M, Donger C, Barhanin J; et al. (1997). "A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome". Nat Genet. 15 (2): 186–9. doi:10.1038/ng0297-186. PMID 9020846.
  56. ↑ Winbo A, Sandström O, Palmqvist R, Rydberg A (2013). "Iron-deficiency anaemia, gastric hyperplasia, and elevated gastrin levels due to potassium channel dysfunction in the Jervell and Lange-Nielsen Syndrome". Cardiol Young. 23 (3): 325–34. doi:10.1017/S1047951112001060. PMID 22805636.
  57. ↑ Rice KS, Dickson G, Lane M, Crawford J, Chung SK, Rees MI; et al. (2011). "Elevated serum gastrin levels in Jervell and Lange-Nielsen syndrome: a marker of severe KCNQ1 dysfunction?". Heart Rhythm. 8 (4): 551–4. doi:10.1016/j.hrthm.2010.11.039. PMID 21118729.
  58. ↑ Salsbury G, Cambridge EL, McIntyre Z, Arends MJ, Karp NA, Isherwood C; et al. (2014). "Disruption of the potassium channel regulatory subunit KCNE2 causes iron-deficient anemia". Exp Hematol. 42 (12): 1053–8.e1. doi:10.1016/j.exphem.2014.07.269. PMC 4271779. PMID 25127743.
  59. ↑ Roepke TK, Anantharam A, Kirchhoff P, Busque SM, Young JB, Geibel JP; et al. (2006). "The KCNE2 potassium channel ancillary subunit is essential for gastric acid secretion". J Biol Chem. 281 (33): 23740–7. doi:10.1074/jbc.M604155200. PMID 16754665.
  60. ↑ "Jervell and Lange-Nielsen Syndrome: Novel Compound Heterozygous Mutations in the KCNQ1 in a Korean Family".
  61. ↑ Goldenberg I, Moss AJ, Zareba W, McNitt S, Robinson JL, Qi M; et al. (2006). "Clinical course and risk stratification of patients affected with the Jervell and Lange-Nielsen syndrome". J Cardiovasc Electrophysiol. 17 (11): 1161–8. doi:10.1111/j.1540-8167.2006.00587.x. PMID 16911578.
  62. ↑ Goldenberg I, Horr S, Moss AJ, Lopes CM, Barsheshet A, McNitt S; et al. (2011). "Risk for life-threatening cardiac events in patients with genotype-confirmed long-QT syndrome and normal-range corrected QT intervals". J Am Coll Cardiol. 57 (1): 51–9. doi:10.1016/j.jacc.2010.07.038. PMC 3332533. PMID 21185501.
  63. ↑ Vincent GM, Schwartz PJ, Denjoy I, Swan H, Bithell C, Spazzolini C; et al. (2009). "High efficacy of beta-blockers in long-QT syndrome type 1: contribution of noncompliance and QT-prolonging drugs to the occurrence of beta-blocker treatment "failures"". Circulation. 119 (2): 215–21. doi:10.1161/CIRCULATIONAHA.108.772533. PMID 19118258.
  64. ↑ Goldenberg I, Moss AJ, Zareba W, McNitt S, Robinson JL, Qi M; et al. (2006). "Clinical course and risk stratification of patients affected with the Jervell and Lange-Nielsen syndrome". J Cardiovasc Electrophysiol. 17 (11): 1161–8. doi:10.1111/j.1540-8167.2006.00587.x. PMID 16911578.
  65. ↑ Schwartz PJ, Spazzolini C, Crotti L, Bathen J, Amlie JP, Timothy K; et al. (2006). "The Jervell and Lange-Nielsen syndrome: natural history, molecular basis, and clinical outcome". Circulation. 113 (6): 783–90. doi:10.1161/CIRCULATIONAHA.105.592899. PMID 16461811.
  66. ↑ Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). "GeneReviews®". PMID 20301579.
  67. ↑ Goldenberg I, Moss AJ, Zareba W, McNitt S, Robinson JL, Qi M; et al. (2006). "Clinical course and risk stratification of patients affected with the Jervell and Lange-Nielsen syndrome". J Cardiovasc Electrophysiol. 17 (11): 1161–8. doi:10.1111/j.1540-8167.2006.00587.x. PMID 16911578.
  68. ↑ Alexander ME, Cecchin F, Walsh EP, Triedman JK, Bevilacqua LM, Berul CI (2004). "Implications of implantable cardioverter defibrillator therapy in congenital heart disease and pediatrics". J Cardiovasc Electrophysiol. 15 (1): 72–6. doi:10.1046/j.1540-8167.2004.03388.x. PMID 15028076.
  69. ↑ Jons C, Moss AJ, Goldenberg I, Liu J, McNitt S, Zareba W; et al. (2010). "Risk of fatal arrhythmic events in long QT syndrome patients after syncope". J Am Coll Cardiol. 55 (8): 783–8. doi:10.1016/j.jacc.2009.11.042. PMID 20170817.
  70. ↑ Goldenberg I, Moss AJ, Zareba W, McNitt S, Robinson JL, Qi M; et al. (2006). "Clinical course and risk stratification of patients affected with the Jervell and Lange-Nielsen syndrome". J Cardiovasc Electrophysiol. 17 (11): 1161–8. doi:10.1111/j.1540-8167.2006.00587.x. PMID 16911578.
  71. ↑ Daneshi A, Ghassemi MM, Talee M, Hassanzadeh S (2008). "Cochlear implantation in children with Jervell, Lange-Nielsen syndrome". J Laryngol Otol. 122 (3): 314–7. doi:10.1017/S0022215107007712. PMID 17498328.
  72. ↑ Siem G, Früh A, Leren TP, Heimdal K, Teig E, Harris S (2008). "Jervell and Lange-Nielsen syndrome in Norwegian children: aspects around cochlear implantation, hearing, and balance". Ear Hear. 29 (2): 261–9. doi:10.1097/aud.0b013e3181645393. PMID 18595190.
  73. ↑ Yanmei F, Yaqin W, Haibo S, Huiqun Z, Zhengnong C, Dongzhen Y; et al. (2008). "Cochlear implantation in patients with Jervell and Lange-Nielsen syndrome, and a review of literature". Int J Pediatr Otorhinolaryngol. 72 (11): 1723–9. doi:10.1016/j.ijporl.2008.07.013. PMID 18805595.
  74. ↑ Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). "GeneReviews®". PMID 20301579.

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