Authors
J. Trip, M.D.
G. Drost, M.D., Ph.D.
H.B. Ginjaar, Ph.D.
B.G.M. van Engelen, M.D., Ph.D.
C.G. Faber, M.D., Ph.D.
Clinical features
The core symptoms of hereditary skeletal muscle channelopathies are muscle stiffness (myotonia) and muscle weakness (transient paresis and periodic paralyses). Myotonia is defined as an abnormal delay in muscle relaxation after voluntary or evoked muscle contractions. Transient paresis, on the other hand, is a short and momentary decline in focal muscle force. Periodic paralyses are spontaneous or provoked attacks of generalised muscle weakness. Thus, in myotonia the skeletal muscle membrane is overexcited and in transient paresis and periodic paralyses it is Read more
Differential diagnosis
The most important differential diagnosis of myotonia is myotonic dystrophy type 1, which is more frequent (prevalence of 2.5-12:100,000 persons in population) than the hereditary skeletal muscle channelopathies.33 The disease has an autosomal dominant inheritance in which the pathology is not only limited to the muscle fibre membrane (sarcolemma) itself. It is a multi system disorder with myotonia, a characteristic distribution of progressive muscle weakness (initially in muscles of the face, throat, neck and distal limb muscles and eventually in proximal limb muscles) and involvement of different organs (heart: conduction defects and arrhythmias; eyes: cataract; smooth muscles: gastro intestinal complaints; lungs: aspiration pneumonia; brain: mental retardation and Read more
Ancillary investigations
In the so-called non-dystrophic myotonias, a subgroup of the hereditary skeletal muscle channelopathies, needle electromyography (EMG) shows myotonic discharges. These discharges are especially triggered by insertion or manipulation of the needle and typically wax and wane in frequency and amplitude, with the changes in frequency causing the characteristic sound of an accelerating motorcycle.17 Myotonic discharges are detectable in Read more
Genetics
The skeletal muscle membrane contains voltage-gated sodium, chloride and calcium channels. Fast moving ions that run through these channels regulate the de- and repolarisation of the muscle membrane. Skeletal muscle sodium channels are important in generating an action potential but also have a role in the repolarisation phase of the membrane (fast inactivation). Skeletal muscle chloride channels play an important role in regulating muscle excitability, as the chloride conductance is essential for the repolarisation phase. After an action potential, the calcium initiate the excitation-contraction coupling that results in a contraction of the muscle. In hereditary skeletal muscle channelopathies one of the above-mentioned processes is disturbed, leading to myotonia, periodic paralysis or a combination of Read more
Therapy
Myotonia responds well to drugs reducing or blocking sodium channels of the muscle fibre membrane.35-37 The agents alleviate myotonia by reducting of the hyperexcitability of the cell membrane. Expert opinion suggests mexiletine as the drug of choice although data supporting the effectiveness of the drug are as yet not available.38 The three double-blind randomised studies that have been conducted were small-scale and restricted to myotonic dystrophy and no such myotonia studies have been performed for hereditary Read more
