Jervell and Lange-Nielsen syndrome: Difference between revisions

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=== Common Symptoms ===
=== Common Symptoms ===
[[File:ECG recording showing prolonged QTc interval..gif|thumb|ECG recording showing prolonged QTc interval. Case courtesy by Senthil Vadivu Arumugam Et Al<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4434209/|title=Syndromic deafness-prevalence, distribution and hearing management protocol in Indian scenario|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref>]]
Common [[symptoms]] of Jervell and Lange-Nielsen syndrome (JLNS) include:
Common [[symptoms]] of Jervell and Lange-Nielsen syndrome (JLNS) include:



Revision as of 20:29, 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

ECG recording showing prolonged QTc interval. Case courtesy by Senthil Vadivu Arumugam Et Al[43]

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.[47]

Laboratory Findings

Laboratory findings consistent with the diagnosis of Jervell and Lange-Nielsen syndrome (JLNS) include:[51][52][53][54]

  • 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[55]

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]

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

  • 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


Template:WikiDoc Sources

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