Which are the causes of Jervell And Lange-Nielsen Syndrome?

Jervell and Lange-Nielsen Syndrome (JLNS) is a rare genetic disorder that affects the heart and hearing. It is an autosomal recessive condition, meaning that both parents must carry the mutated gene for their child to inherit the syndrome. JLNS is characterized by two main symptoms: a prolonged QT interval on an electrocardiogram (ECG) and severe hearing loss.

The primary cause of JLNS is mutations in two specific genes: KCNQ1 and KCNE1. These genes provide instructions for making proteins that are essential for the normal functioning of the heart and inner ear. Mutations in these genes disrupt the normal flow of potassium ions in the cells, leading to abnormalities in the electrical activity of the heart and impairments in the development and function of the inner ear.

The KCNQ1 gene mutation is responsible for approximately 90% of JLNS cases. This gene produces a protein called Kv7.1, which forms channels that allow potassium ions to flow in and out of cells. These channels play a crucial role in regulating the electrical activity of the heart. Mutations in KCNQ1 disrupt the normal functioning of these channels, leading to a prolonged QT interval on an ECG. A prolonged QT interval increases the risk of life-threatening cardiac arrhythmias, such as ventricular fibrillation, which can cause fainting, seizures, or even sudden cardiac arrest.

The KCNE1 gene mutation accounts for the remaining 10% of JLNS cases. This gene produces a protein called minK, which interacts with the Kv7.1 protein to form functional potassium channels. Mutations in KCNE1 also disrupt the normal functioning of these channels, leading to a prolonged QT interval and an increased risk of cardiac arrhythmias.

It is important to note that individuals with JLNS have a higher risk of experiencing sudden cardiac death due to the increased susceptibility to life-threatening arrhythmias. Therefore, early diagnosis and appropriate management are crucial to prevent cardiac events. Treatment options may include medications to regulate heart rhythm, implantation of a cardioverter-defibrillator (ICD) to deliver electric shocks if a dangerous arrhythmia occurs, and cochlear implants to improve hearing.