Pathology of the Week – April 9th
Jervell and Lange-Nielsen syndrome. Medicalese: first described in 1957 by Anton Jervell and Fred Lange-Nielsen. Short forms: JLNS or J-LN syndrome
JLNS is the first in a weekly series of uncommon pathologies I will post. I first heard about this cardioauditory (two words not usually together) disorder from a February, 2010 Dr. Venkatesan blog post. Jervell and Lange-Nielsen syndrome (JLNS) is a genetic disorder that affects potassium channels in the heart and inner ear. This affects cellular repolarization and lengthens the cardiac action potential causing prolonged QT intervals and neural deafness. JLNS is the most severe variant of the congenital long QT disorders with over 90% of patients becoming symptomatic and 25% suffering sudden death. In a sample of 186 patients 50% had a cardiac event before age three and only 5% neared adulthood symptomless. See this Circulation article (free access) as well as this thorough review by Tranebjaerg et al.
Signs and Symptoms
JLNS is usually diagnosed after a congenitally deaf child experiences repeated syncopal episodes at a young age. The two cardinal symptoms are profound hearing loss present from birth and a wide QTc interval (at least 500 ms). Long QT disorders predispose a patient to deadly cardiac arrhythmias such as Torsades, Vtach and Vfib.
JLNS is an autosomal recessive birth defect. This means both parents must be carriers of the mutated sexless (autosomal) gene. The above study did find, in 186 patients, a consanguinity rate of 35%. This greatly increases the risk of recessive genetic disorders. The mutation occurs on genes which would produce proteins that coassemble to form specific potassium channels in cardiac and inner ear cells. These cells normally pump positively charged potassium ions back out of the cell to aide in repolarization.
Management and Treatment
JLNS has an extremely poor patient outcome with a mean life expectancy of around 8 years. Pharmacologically beta-blockers are the most commonly prescribed drug. Unfortunately 51% of patients will still suffer a cardiac event (arrest or sudden death). Mean age at death for patients on Beta Blockers remains just 8 years. Cochlear implants are effective in restoring hearing and do not affect pacemaker activity. Patients are also usually advised to avoid activities that would stimulate sympathetic arousal of the heart such as sports, scary movies and even cold water.
Implications for Prehospital Care
This disorder is relatively rare, the authors of the 186 patient study had to assemble the sample from over a dozen countries in numerous continents. JLNS is something to consider for a differential diagnosis of a syncopal paediatric patient with a history of hearing loss at birth. It is also helpful in learning the long QT disorders.