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.

Classification

• Jervell and Lange-Nielsen syndrome (JLNS) may be classified according into two subtypes:

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:

• 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

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

KCNQ1

• KCNQ1 gene normally consists of 16 exons and have a general spanning of 400 kb.
• 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.
• 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.
• 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:
  • KCNQ1
  • KCNE1
  • [Gene3]

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.