Jervell and Lange-Nielsen syndrome

Revision as of 15:24, 14 November 2019 by Gunnam (talk | contribs) (→‎Pathogenesis)
Jump to navigation Jump to search
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

  • Jervell and Lange-Nielsen syndrome (JLNS) may be classified according into two subtypes:[2][3][4]
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 the slow potassium channel currents were stimulated by the sound, when stimulated the potassium from the scala media passes through the apex of the hair cells.
  • The potassium action potential then depolarise 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 depolarize and the currents are sent centrally where they are received as sound.

Pathogenesis

KCNQ1

  • KCNQ1 gene normally consists of 16 exons and have a general spanning of 400 kb.[7]
  • 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.[8]
  • 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.[9]
  • 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 autosomal recessive pattern.
  • Genes involved in the pathogenesis of Jervell and Lange-Nielsen syndrome (JLNS) include:

OR

The development of [disease name] is the result of multiple genetic mutations such as:

  • [Mutation 1]
  • [Mutation 2]
  • [Mutation 3]

Causes


Life-threatening Causes[edit | edit source]

  • Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated. There are no life-threatening causes of disease name, however complications resulting from untreated disease name is common.
  • Life-threatening causes of [symptom/manifestation] include [cause1], [cause2], and [cause3].
  • [Cause] is a life-threatening cause of [disease].

Common Causes[edit | edit source]

Common causes of [disease name] may include:

  • [Cause1]
  • [Cause2]
  • [Cause3]

OR

  • [Disease name] is caused by an infection with [pathogen name].
  • [Pathogen name] is caused by [pathogen name].

Less Common Causes[edit | edit source]

Less common causes of [disease name] include:

  • [Cause1]
  • [Cause2]
  • [Cause3]

Genetic Causes[edit | edit source]

  • [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

Template:WikiDoc Sources

References

  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. ↑ 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.
  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.
  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.
  5. ↑ Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). "GeneReviews®". PMID 20301579.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.

Template:WH Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=Jervell_and_Lange-Nielsen_syndrome&oldid=1589175"