March 13, 2015
The ‘sodium channel, voltage-gated, type IV, alpha subunit’ gene, more commonly referred to as the SCN4A gene, is a critical gene in the production of the alpha subunit of sodium channels. Located on chromosome 17q23.3, mutations or dysfunction of the SCN4A gene have been shown to be the pathological in several inherited muscle diseases. With membrane depolarization, this sodium channel opens and allows for a very brief influx of sodium ions. This rapid influx, which only occurs over milliseconds, is subsequently felt to start the initial repolarization phase, given the rapid cessation of sodium influx. Numerous inherited muscle diseases, including hyperkalemic periodic paralysis, paramyotonia congenita and potassium-aggravated myotonia are all associated with abnormalities of the SCN4A gene. Dysfunction of this channel secondary to SCN4A mutations often results in prolonged influx of sodium ions, ultimately leading to the clinical phenotype of sustained muscle contraction, or myotonia. Special consideration should be taken with anesthetic agents in patients with SCN4A-related diseases, as their clinical syndrome can be acutely worsened due to channel dysfunction.
- Bandschapp O and Iaizzo PA. Pathophysiologic and anesthetic considerations for patients with myotonia congenital or periodic paralyses. Pediatric Anesthesia 2013; 23: 824-833.
Submitted by James Addington, MD, Resident Physician, Department of Neurology University of Virginia
Dr. Addington is a member of the Resident and Fellow Section of Neurology.