What is the overview of clinical information for the United States Medical Licensing Examination (USMLE) regarding Jervell and Lange-Nielsen syndrome and Romano-Ward syndrome?

From the Guidelines

Jervell and Lange-Nielsen syndrome and Romano-Ward syndrome are both forms of Long QT syndrome (LQTS), a cardiac channelopathy that predisposes patients to life-threatening ventricular arrhythmias, with Romano-Ward syndrome being the more common autosomal dominant form and Jervell and Lange-Nielsen syndrome being the rarer autosomal recessive form with congenital sensorineural deafness. The most common genetic mutations involve KCNQ1 (LQT1), KCNH2 (LQT2), and SCN5A (LQT3), affecting potassium and sodium channels in cardiac myocytes, as noted in the 2015 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death 1. Management for both conditions includes:

• Beta-blockers (propranolol, nadolol) as first-line therapy, as recommended by the 2015 ESC guidelines 1
• Avoidance of QT-prolonging medications, which is crucial in preventing torsades de pointes, a life-threatening arrhythmia associated with LQTS
• Electrolyte monitoring, to prevent hypokalemia and hypomagnesemia, which can trigger arrhythmias
• Lifestyle modifications, including limiting strenuous exercise, especially in patients with LQT1, and avoiding loud noises in patients with LQT2, as recommended by the 2015 ESC guidelines 1 High-risk patients may require implantable cardioverter-defibrillators, as noted in the 2015 ESC guidelines 1. For USMLE purposes, it is essential to remember the inheritance patterns, associated deafness in Jervell and Lange-Nielsen, the risk of torsades de pointes, and the importance of beta-blockers in management, as highlighted in the 2015 ESC guidelines 1. Key points to consider include:
• The annual rate of sudden cardiac death in patients with untreated LQTS is estimated to be between 0.3% and 0.9% 1
• The mean age at presentation is 14 years, and the condition is often triggered by adrenergic activation 1
• Genetic screening identifies a disease-causing mutation in 75% of LQTS cases, and three main genes (KCNQ1, KCNH2, and SCN5A) account for 90% of positively genotyped cases, as noted in the 2015 ESC guidelines 1

From the Research

Jervell and Lange-Nielsen Syndrome

• Jervell and Lange-Nielsen syndrome (JLNS) is characterized by congenital deafness, very long QT intervals, and high risk of life-threatening arrhythmias 2.
• Patients with JLNS exhibit severe phenotypes and are at risk of recurrent syncope, malignant ventricular arrhythmias, and sudden death 3.
• The syndrome is inherited in an autosomal recessive pattern and is associated with mutations in the KCNQ1 and KCNE1 genes 4, 5.
• Treatment strategies for JLNS include high doses of beta-blocker medication, left cardiac sympathetic denervation, and ICD placement, which can be challenging in young children 2.
• Atrial pacing combined with beta-blocker therapy has been shown to be a favorable approach in young high-risk patients with JLNS, potentially preventing life-threatening arrhythmias and acting as a bridge to insertion of a 2-chamber ICD 2.

Romano-Ward Syndrome

• Romano-Ward syndrome (RWS) is characterized by a prolonged QT interval, autosomal-dominant inheritance, and no deafness 3.
• RWS is also associated with mutations in the KCNQ1 and KCNE1 genes, but in a heterozygous form 4, 6.
• Patients with RWS are at risk of recurrent syncope, malignant ventricular arrhythmias, and sudden death, similar to those with JLNS 3.
• The diagnosis and treatment of RWS are similar to those of JLNS, with a focus on managing the risk of life-threatening arrhythmias and preventing sudden death 5.

Comparison of Jervell and Lange-Nielsen Syndrome and Romano-Ward Syndrome

• Both JLNS and RWS are associated with long QT intervals and an increased risk of life-threatening arrhythmias 3, 4.
• The main difference between the two syndromes is the presence of congenital deafness in JLNS, which is not seen in RWS 3.
• The genetic basis of the two syndromes also differs, with JLNS being inherited in an autosomal recessive pattern and RWS being inherited in an autosomal dominant pattern 4, 5.
• The treatment strategies for the two syndromes are similar, with a focus on managing the risk of life-threatening arrhythmias and preventing sudden death 2, 5.