Jervell and Lange-Nielsen syndrome: Difference between revisions

	Jervell and Lange-Nielsen syndrome;
ICD-9	426.82
OMIM	220400
DiseasesDB	7249
MeSH	D029593

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Revision as of 23:35, 16 November 2019

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

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

Jervell and Lange-Nielsen syndrome is a rare autosomal recessive condition that leads to sensorineural deafness, 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.

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]

Classification

Jervell and Lange-Nielsen syndrome (JLNS) may be classified according into two subtypes:^[2]^[3]^[4]^[5]


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:^[6]

Both KCNQ1 and KCNE1 genes encodes for the slow potassium channel currents of the cochlea and the heart.
Normally the slow potassium channel currents were stimulated by the sound, when stimulated the potassium from the scala media passes the action potential through the apex of the hair cells.
The potassium action potential then depolarises the hair cells.
Once depolarised there is a release calcium-channel-induced release of neurotransmitter.
The neurotransmitter then passes along with the auditory nerve and then depolarizes and the currents are sent centrally where they are received as sound.

Pathogenesis

It is understood that Jervell and Lange-Nielsen syndrome (JLNS) is the result of mutations in the gene KCNQ1 and KCNE1.^[7]

KCNQ1

KCNQ1 gene normally consists of 16 exons and have a general spanning of 400 kb.^[8]^[9]^[10]
The normal gene product of KCNQ1 gene is potassium voltage-gated channel subfamily KQT member 1.
When KCNQ1 gene undergoes frameshift mutation it results in yielding truncated protein.
Then the truncated protein either delete or duplicate the exons of the KCNQ1 gene and results in abnormal gene product which is known to result in long QT syndrome.

KCNE1

KCNE1 gene normally consists of 3 exons and have a general spanning of 40 kb.^[11]^[12]^[13]^[14]^[15]
The normal gene product of KCNE1 gene is potassium voltage-gated channel subfamily E member 1.
Potassium voltage-gated channel subfamily E member 1 is also called as minK potassium channel protein beta subunit.^[16]
When KCNE1 gene undergoes missense mutation it results in yielding truncated protein.
Then the truncated protein results in impairing potassium channel function, which is known to result in long QT syndrome.

Genetics

Jervell and Lange-Nielsen syndrome (JLNS) is transmitted in a autosomal recessive pattern.

Genes involved in the pathogenesis of Jervell and Lange-Nielsen syndrome (JLNS) include:
- KCNQ1
- KCNE1

Causes

Genetic Causes

Jervell and Lange-Nielsen syndrome (JLNS) is caused by a mutation in the KCNQ1 and KCNE1 genes.

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 (SIDS).^[17]^[18]^[19]^[20]^[21]

Epidemiology and Demographics

Incidence

The incidence/prevalence of [disease name] is approximately [number range] per 100,000 individuals worldwide.
In [year], the incidence/prevalence of [disease name] was estimated to be [number range] cases per 100,000 individuals worldwide.

Prevalence

The incidence/prevalence of [disease name] is approximately [number range] per 100,000 individuals worldwide.
In [year], the incidence/prevalence of [disease name] was estimated to be [number range] cases per 100,000 individuals worldwide.
The prevalence of [disease/malignancy] is estimated to be [number] cases annually.

Case-fatality rate/Mortality rate

In [year], the incidence of [disease name] is approximately [number range] per 100,000 individuals with a case-fatality rate/mortality rate of [number range]%.
The case-fatality rate/mortality rate of [disease name] is approximately [number range].

Age

Patients of all age groups may develop [disease name].
The incidence of Jervell and Lange-Nielsen syndrome (JLNS) increases with age; the median age at diagnosis is 20 years.
Jervell and Lange-Nielsen syndrome (JLNS) commonly affects individuals of younger age.
[Chronic disease name] is usually first diagnosed among [age group].
[Acute disease name] commonly affects [age group].

Race

There is no racial predilection to [disease name].
[Disease name] usually affects individuals of the [race 1] race. [Race 2] individuals are less likely to develop [disease name].

Gender

[Disease name] affects men and women equally.
[Gender 1] are more commonly affected by [disease name] than [gender 2]. The [gender 1] to [gender 2] ratio is approximately [number > 1] to 1.

Region

The majority of [disease name] cases are reported in [geographical region].

[Disease name] is a common/rare disease that tends to affect [patient population 1] and [patient population 2].

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Treatment

Template:WikiDoc Sources

References

↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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
↑ Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). "GeneReviews®". PMID 20301579.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). "GeneReviews®". PMID 20301308.
↑ 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.
↑ 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.
↑ 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.
↑ 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.

Template:WH Template:WS

[pmid10704188-1] 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.

[pmid11140949-2] 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.

[pmid16461811-3] 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.

[pmid107041882-4] 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.

[pmid12180152-5] 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

[pmid20301579-6] Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). "GeneReviews®". PMID 20301579.

[pmid107041883-7] 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.

[pmid12051962-8] 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.

[pmid17993327-9] 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.

[pmid11874988-10] 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.

[pmid14679187-11] 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.

[pmid12923204-12] 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.

[pmid16050264-13] 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.

[pmid118749882-14] 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.

[pmid179933272-15] 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.

[pmid19219384-16] 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.

[pmid20301308-17] Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). "GeneReviews®". PMID 20301308.

[pmid11710892-18] 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.

[pmid17210839-19] 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.

[pmid11136691-20] 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.

[pmid16012827-21] 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.

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@@ Line 67: / Line 67: @@
 * ''[[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>
 *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 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]].
 '''''[[KCNE1]]'''''