Jervell and Lange-Nielson syndrome (JLNS) – KCNQ1 and KCNE1 genes

Baby Detect > Cardiology > Jervell and Lange-Nielson syndrome (JLNS) – KCNQ1 and KCNE1 genes

#OMIM220400 – https://omim.org/entry/220400

Also known as: Congenital deafness and functional heart disease; Prolonged QT interval in EKG and sudden death; Cardioauditory syndrome of Jervell and Lange-Nielsen; Surdo-cardiac syndrome

1. The Disease:

A rare, severe, familial long QT syndrome characterized by congenital profound bilateral sensorineural hearing loss, a long QT interval on electrocardiogram and life-threatening ventricular tachyarrhythmias. The disease is very rare. Prevalence is unknown and varies depending on the population studied (1/100,000-1/1,000,000) but is more common in countries in which consanguineous marriage is frequent.

2. The symptoms:

Almost 50% of patients become symptomatic before age of 3 years. Lack of early signs or symptoms does not exclude the diagnosis.

  • The typical presentation of Jervell and Lange-Nielsen syndrome (JLNS) is a child with congenital deafness, who experiences syncopal episodes during periods of stress, exercise, or fright.
  • Deafness is congenital, bilateral, profound, and sensorineural. The QT interval is usually markedly prolonged (>500 ms) and associated with tachyarrhythmias (including ventricular tachycardia, episodes of Torsades de Pointes (TdP) ventricular tachycardia and ventricular fibrillation) that may cause syncope or sudden death. It is one of the most severe forms of LQTS.
  • Patients become symptomatic much earlier than in any other LQTS form, with the exception of calmodulin-related LQTS. Almost 90% of patients have cardiac events triggered by intense or sudden emotion, competitive sports, fright or jumping into cold water.

3. Actions to take in case of early diagnosis

  • Babies with a positive genetic test (biallelic pathogenic variants – homozygous or compound heterozygous – in the KCNQ1 or KCNE1 genes), should continue breastfeeding
  • The diagnosis is based on genetic results, presence of congenital sensorineural deafness and long QT intervals.
  • JLNS is a lifelong condition that requires lifetime management and regular follow-up with a paediatrician specialist in cardiology, geneticist, and a multidisciplinary approach to care.
  • Hearing loss in JLNS benefits from cochlear implantation.
  • The main goal in management of JLNS is prevention of syncope, cardiac arrest and sudden death.
  • The therapeutic approach is complicated by the early age at which most of the patients become symptomatic. As the efficacy of beta-blockers in JLNS while good is not complete, an implantable cardioverter defibrillator (ICD) should be seriously considered and, if necessary, left cardiac sympathetic denervation (LCSD). However, even with additional therapies (pacemakers, ICDs, and LCSD), more than 50% of patients experience additional symptoms and are at risk of sudden death.
  • Family members should be trained in cardiopulmonary resuscitation as up to 95% of patients with JLNS have a cardiac event before adulthood.
  • Genetic counselling is highly recommended for family planning and evaluation of at-risk first-degree family members.

4. For more information

Orphanet: https://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=12056&Disease_Disease_Search_diseaseGroup=Jervell-and-Lange-Nielsen-Syndrome&Disease_Disease_Search_diseaseType=Pat&Disease(s)/group%20of%20diseases=Jervell-and-Lange-Nielsen-syndrome&title=Jervell%20and%20Lange-Nielsen%20syndrome&search=Disease_Search_Simple

Biblio: https://www.ncbi.nlm.nih.gov/books/NBK1405/