Ion channel myopathies consist of disorders featuring paralysis and hypotonia. Unlike myotonic dystrophy or other causes of myopathies, ion channel myopathies are a group of genetic defects in sodium, chloride, and calcium ion channels that are present in the myocyte membranes, leading to myotonia. Myotonic disorders have multiple etiologies and some disorders may be considered a channelopathy if ion channel conductance is the culprit in the disease, but the most common cause myotonia is not due to an ion channelopathy but a defect in the protein kinase production.
Ion channel myopathies are part of a family of genetic disorders known as “periodic paralysis” (PP), whereby mutations in various ion channels of the cellular membrane alter electrolyte conductance, leading to muscle weakness in irregular intervals (Table 117-1).
TABLE 117-1Channel Defects and Associated Diseases ||Download (.pdf) TABLE 117-1 Channel Defects and Associated Diseases
|Voltage-gated sodium channel ||Hyperkalemic PP, paramyotonia congenita, potassium-aggravated myotonia |
|Voltage-dependent calcium channel ||Hypokalemic PP |
|Voltage-gated chloride channel ||Normokalemic PP, Becker and Thomsen myotonia congenitas |
CONGENITAL MYOTONIA (MYOTONIA CONGENITA)
Myotonia congenita is a rare inherited disease that is characterized by myotonia, muscle stiffness, and abnormal muscle hypertrophy. The disease can be classified into two types based upon the transmission pattern, severity of symptoms, and age of onset. The Becker type, which is inherited in an autosomal recessive pattern, most commonly manifests between the ages of 4 and 12, and in rare cases, there have been reports of manifestation as late as 18 years of age. Thomsen disease is inherited in an autosomal dominant pattern and generally shows the age of onset as early as infancy, however, most commonly between ages of 2 and 3 years. The symptoms in Thomsen disease are less severe and do not progress after onset, whereas Becker’s disease can present as generalized muscle stiffness. The mutation in both diseases resides in the CLCN1 muscle chloride channel gene whose locus is on chromosome 7q35. The reported incidence for myotonia congenita is estimated at 6:100,000, with Becker’s being twice as common as Thomson’s.
A defect in chloride channels results in decreased conductance of chloride into the muscle cell, resulting in a slowed repolarization of the cell membrane. Diagnosis is made clinically and confirmed with genetic studies. Common presentations include inability to relax after contracting a muscle, for instance, inability to release a handshake, blepharospasm, and diffuse hypertrophy of muscles (buttocks, neck, back, shoulders). Tendon reflex stimulation often elicits a sustained contraction. Muscle stiffness is usually painless and can be relieved by exercise, termed the “warm-up effect.” Muscle biopsy shows no signs of dystrophy, while creatine kinase levels may be elevated. Electromyographic tracings also show myotonic discharge. Unlike in myotonic dystrophy, there is no cardiac involvement.