Clinical Guidance

Among 63 individuals who were genotyped, 33% were compound heterozygotes . No clinical difference was evident between persons with at least one inactivating variant (e.g., insertion/deletion, splice variant, truncation) and those with missense variants.

Source: GeneReviews — "Jervell and Lange-Nielsen Syndrome"

Diagnostic Criteria

Suggestive Findings

Jervell and Lange-Nielsen syndrome (JLNS) should be suspected in a proband with the following features:

• Profound congenital sensorineural deafness

• Long QTc interval (500 msec), often manifest as syncope, most often elicited by emotion or exercise. Note: Normal QTc interval in males is 440 msec and in post-pubertal females is 460 msec.

Establishing the Diagnosis

The diagnosis of JLNS is established in a proband with the above suggestive findings. Identification of biallelic pathogenic (or likely pathogenic) variants in either KCNQ1 or KCNE1 confirms the diagnosis, particularly if clinical features are inconclusive. Note: (1) It is not currently known how many children with molecularly confirmed JLNS have a borderline QTc interval (440-500 msec) or a normal QTc interval.

Source: GeneReviews — "Jervell and Lange-Nielsen Syndrome"

Differential Diagnosis

Deafness and prolonged QTc with or without long QT syndrome (LQTS) both have multiple etiologies, including genetic and environmental causes. In many individuals with both deafness and prolonged QTc (or LQTS), the deafness and prolonged QTc (or LQTS) have separate etiologies. All of these possibilities must be considered in each affected individual, particularly in the absence of parental consanguinity or an affected sib. The following considerations are relevant in an individual who has both deafness and prolonged QTc:

Source: GeneReviews — "Jervell and Lange-Nielsen Syndrome"

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with Jervell and Lange-Nielsen syndrome (JLNS), the following evaluations are recommended if they have not already been completed:

• Formal audiology evaluation for extent of hearing loss

• Cardiac examination including calculation of QTc

• A three-generation family history that focuses on cardiac disease, syncope, and hearing ability

• Complete blood count to screen for anemia. If anemia is present, screening for iron deficiency is recommended.

• Consultation with a clinical geneticist

Treatment of Manifestations

Hearing loss in JLNS may be treated successfully with cochlear implantation, an intervention that does not interfere with bipolar pacemakers (see Genetic Hearing Loss Overview). To date, the cumulative published experience includes approximately 20 individuals with JLNS who have received cochlear implantation. Of note, the diagnosis of JLNS was only verified with molecular genetic testing in four Norwegian individuals, all of whom had pathogenic variants in KCNQ1. An increase in sound-related syncopal episodes was noted after cochlear implantation in one child . Note: Although cochlear implantation appears to be safe, special precautions are necessary during anesthesia because of the increased risk for cardiac arrhythmia . One affected individual died during a perioperative cardiac arrest . Cardiac issues.

Source: GeneReviews — "Jervell and Lange-Nielsen Syndrome"

Clinical Guidance

The following should be avoided:

• Drugs that cause further prolongation of the QT interval or provoke torsade de pointes; see www.crediblemeds.org for a complete and updated list (registration required).

• Triggers for intense or sudden emotion; activities that are known to precipitate syncopal events in individuals with long QT syndrome, including:

• Competitive sports

• Amusement park rides

• Frightening movies

• Jumping into cold water

A cardiologist should make recommendations for activity restrictions based on the effectiveness of medical intervention.

Source: GeneReviews — "Jervell and Lange-Nielsen Syndrome"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Jervell and Lange-Nielsen Syndrome"

Surveillance Guidelines

Beta-blocker dose should be regularly assessed for efficacy and adverse effects, and doses altered as needed. Because dose adjustment is especially important in growing children, evaluation is appropriate every three to six months during rapid growth phases. Regular, periodic evaluation of implantable cardioverter defibrillators (ICDs) for inappropriate shocks and pocket or lead complications is indicated.

Source: GeneReviews — "Jervell and Lange-Nielsen Syndrome"