Jervell and Lange-Nielsen Syndrome

Clinical characteristics: Jervell and Lange-Nielsen syndrome (JLNS) is characterized by congenital profound bilateral sensorineural hearing loss and long QTc, usually >500 msec. Prolongation of the QTc interval is associated with tachyarrhythmias, including ventricular tachycardia, episodes of torsade de pointes ventricular tachycardia, and ventricular fibrillation, which may culminate in syncope or sudden death. Iron-deficient anemia and elevated levels of gastrin are also frequent features of JLNS. The classic presentation of JLNS is a deaf child who experiences syncopal episodes during periods of stress, exercise, or fright. Fifty percent of individuals with JLNS had cardiac events before age three years. More than half of untreated children with JLNS die before age 15 years.

Diagnosis/testing: The diagnosis of JLNS is established in a child with congenital sensorineural deafness, long QT interval, and presence of biallelic pathogenic variants in either KCNQ1 or KCNE1.

Management: Treatment of manifestations: Cochlear implantation to treat hearing loss; beta-adrenergic blockers for long QT interval (Note: Beta-blocker treatment is only partially effective.); implantable cardioverter defibrillators (ICDs) for those with a history of cardiac arrest and/or failure to respond to other treatments; ensure availability of automated external defibrillators where appropriate; standard treatment for those with iron-deficiency anemia.

Prevention of secondary complications: Special precautions during anesthesia are necessary because of the increased risk for cardiac arrhythmia.

Surveillance: Beta-blocker dose should be regularly assessed for efficacy and adverse effects, with evaluation every three to six months during rapid growth phases; periodic evaluations of ICDs for inappropriate shocks and pocket or lead complications.

Agents/circumstances to avoid: Drugs that cause further prolongation of the QT interval; activities known to precipitate syncopal events in persons with long QT syndrome.

Evaluation of relatives at risk: Hearing evaluation by standard newborn hearing screening programs and electrocardiograms for at-risk sibs; molecular genetic testing to confirm the diagnosis if the pathogenic variants in an affected family member are known.

Pregnancy management: Consideration should be given as to whether a mother who has a fetus affected with JLNS herself has long QT syndrome.

Other: Training for family members in cardiopulmonary resuscitation; use of an ID bracelet explaining the diagnosis; notifying local emergency medical services of high-risk persons with JLNS.

Genetic counseling: JLNS is inherited in an autosomal recessive manner. Parents of a child with JLNS are usually heterozygotes; rarely, only one parent is heterozygous (i.e., the proband has one inherited and one de novo pathogenic variant). Parents may or may not have the long QT syndrome (LQTS) phenotype. At conception, each sib of an affected individual usually has a 25% chance of being affected with JLNS, a 50% chance of being a carrier of a JLNS-causing pathogenic variant and potentially at risk for LQTS, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the pathogenic variants in the family are known.