Jervell and Lange-Nielsen syndrome
| Jervell and Lange-Nielsen syndrome | |
| ICD-9 | 426.82 |
|---|---|
| OMIM | 220400 |
| DiseasesDB | 7249 |
| MeSH | D029593 |
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
| 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:[5]
- 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.[6]
- KCNQ1 gene normally consists of 16 exons and have a general spanning of 400 kb.[7][8][9]
- 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 gene normally consists of 3 exons and have a general spanning of 40 kb.[10][11][12][13][14]
- 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.[15]
- 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:
Causes
Genetic Causes
- [Disease name] is caused by a mutation in the [gene name] gene.
Differentiating Xyz from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
Treatment
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.
- ↑ 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.