Jervell and Lange-Nielsen syndrome

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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


References

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  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.
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