Jervell and Lange-Nielsen syndrome: Difference between revisions

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== Overview ==
== Overview ==
[[File:Autosomal recessive gene.png|alt=autosomal recessive pattern of inheritance|thumb|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, <nowiki>https://commons.wikimedia.org/w/index.php?curid=1840082</nowiki>]]
Jervell and Lange-Nielsen syndrome is a rare [[autosomal recessive]] condition that leads to [[Sensorineural hearing loss|sensorineural deafness]], abnormal [[ventricular]] [[myocardial]] [[repolarization]] with results in [[long QT syndrome]] ([[Long QT syndrome|LQTS]]) and other [[cardiac]] events. Jervell and Lange-Nielsen syndrome is due to '''''[[KCNQ1]]''''' or '''''[[KCNE1]]''''' [[Gene mutation|gene mutations]]. The range of [[symptoms]] and severity of [[symptoms]] in Jervell and Lange-Nielsen syndrome differs from [[patient]] to [[patient]].
Jervell and Lange-Nielsen syndrome is a rare [[autosomal recessive]] condition that leads to [[Sensorineural hearing loss|sensorineural deafness]], abnormal [[ventricular]] [[myocardial]] [[repolarization]] with results in [[long QT syndrome]] ([[Long QT syndrome|LQTS]]) and other [[cardiac]] events. Jervell and Lange-Nielsen syndrome is due to '''''[[KCNQ1]]''''' or '''''[[KCNE1]]''''' [[Gene mutation|gene mutations]]. The range of [[symptoms]] and severity of [[symptoms]] in Jervell and Lange-Nielsen syndrome differs from [[patient]] to [[patient]].



Revision as of 16:48, 26 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

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 with 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.

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.[29][30][31]
  • 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][32]

Age

  • The incidence of Jervell and Lange-Nielsen syndrome (JLNS) increases with age; the median age at diagnosis is 6.8 years.[33][34]
  • 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.[35]

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:[36]
    • 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

Common symptoms of Jervell and Lange-Nielsen syndrome (JLNS) include:

Physical Examination

HEENT

  • All patients with Jervell and Lange-Nielsen syndrome (JLNS) are positive for profound bilateral congenital sensorineural deafness.[44][45]
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.[46]

Laboratory Findings

Laboratory findings consistent with the diagnosis of Jervell and Lange-Nielsen syndrome (JLNS) include:[50][51]

  • Anemia: patients with Jervell and Lange-Nielsen syndrome (JLNS) are more prone to develop anemia especially iron deficiency anemia
  • Hypergastrinemia is due to the potassium channels defect
  • Increased gastrin levels due to gastric hyperplasia

Electrocardiogram

ECG in Jervell and Lange-Nielsen syndrome shows markedly prolonged corrected QT interval (QTc). Case courtesy by Jae Suk Baek et al[52]

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]

Imaging Findings

There are no other imaging findings associated with Jervell and Lange-Nielsen syndrome (JLNS).

Treatment

Medical Therapy

  • Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
  • Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].
  • Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
  • Patients with Jervell and Lange-Nielsen syndrome (JLNS) are treated with beta-adrenergic blockers as the first line in the management of the disease.
  • In patients with Jervell and Lange-Nielsen syndrome (JLNS) despite treated with the beta-blockers risk of cardiac events still persists.
  • Propranolol and nadolol are the beta-blockers of choice when treating a patient with Jervell and Lange-Nielsen syndrome (JLNS).

Disease Name

  • 1 Stage 1 - Name of stage
    • 1.1 Specific Organ system involved 1
      • 1.1.1 Adult
        • Preferred regimen (1): drug name 100 mg PO q12h for 10-21 days (Contraindications/specific instructions)
        • Preferred regimen (2): drug name 500 mg PO q8h for 14-21 days
        • Preferred regimen (3): drug name 500 mg q12h for 14-21 days
        • Alternative regimen (1): drug name 500 mg PO q6h for 7–10 days
        • Alternative regimen (2): drug name 500 mg PO q12h for 14–21 days
        • Alternative regimen (3): drug name 500 mg PO q6h for 14–21 days
      • 1.1.2 Pediatric
        • 1.1.2.1 (Specific population e.g. children < 8 years of age)
          • Preferred regimen (1): drug name 50 mg/kg PO per day q8h (maximum, 500 mg per dose)
          • Preferred regimen (2): drug name 30 mg/kg PO per day in 2 divided doses (maximum, 500 mg per dose)
          • Alternative regimen (1): drug name10 mg/kg PO q6h (maximum, 500 mg per day)
          • Alternative regimen (2): drug name 7.5 mg/kg PO q12h (maximum, 500 mg per dose)
          • Alternative regimen (3): drug name 12.5 mg/kg PO q6h (maximum, 500 mg per dose)
        • 1.1.2.2 (Specific population e.g. 'children < 8 years of age')
          • Preferred regimen (1): drug name 4 mg/kg/day PO q12h(maximum, 100 mg per dose)
          • Alternative regimen (1): drug name 10 mg/kg PO q6h (maximum, 500 mg per day)
          • Alternative regimen (2): drug name 7.5 mg/kg PO q12h (maximum, 500 mg per dose)
          • Alternative regimen (3): drug name 12.5 mg/kg PO q6h (maximum, 500 mg per dose)
    • 1.2 Specific Organ system involved 2
      • 1.2.1 Adult
        • Preferred regimen (1): drug name 500 mg PO q8h
      • 1.2.2 Pediatric
        • Preferred regimen (1): drug name 50 mg/kg/day PO q8h (maximum, 500 mg per dose)
  • 2 Stage 2 - Name of stage
    • 2.1 Specific Organ system involved 1
      Note (1):
      Note (2):
      Note (3):
      • 2.1.1 Adult
        • Parenteral regimen
          • Preferred regimen (1): drug name 2 g IV q24h for 14 (14–21) days
          • Alternative regimen (1): drug name 2 g IV q8h for 14 (14–21) days
          • Alternative regimen (2): drug name 18–24 MU/day IV q4h for 14 (14–21) days
        • Oral regimen
          • Preferred regimen (1): drug name 500 mg PO q8h for 14 (14–21) days
          • Preferred regimen (2): drug name 100 mg PO q12h for 14 (14–21) days
          • Preferred regimen (3): drug name 500 mg PO q12h for 14 (14–21) days
          • Alternative regimen (1): drug name 500 mg PO q6h for 7–10 days
          • Alternative regimen (2): drug name 500 mg PO q12h for 14–21 days
          • Alternative regimen (3):drug name 500 mg PO q6h for 14–21 days


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