This chapter considers a category of disorders that is characterized
by disturbances of the electrical excitability of the skeletal muscle
membrane. Although the main manifestations are episodes of generalized
paralysis and myotonia, there are many others. The myotonias have
been historically categorized as a special group of muscle diseases
unified by the clinical sign of myotonia and were aligned in older
classifications with the muscular dystrophies. This view was based
on myotonia as it was understood in the classic form of myotonic
dystrophy, a subject discussed in Chap. 50.
Similarly, before fundamental knowledge of their mechanism was revealed,
the periodic paralyses (better called episodic paralysis)
were considered to be metabolic diseases of muscle. However, it
has become evident that most diseases that feature prominent myotonia
and the processes that cause episodic muscular paralysis are neither
degenerative nor dystrophic. Clinical and electrophysiologic studies
show that myotonia is an elemental feature of many nondystrophic
conditions, foremost among them are the hyperkalemic form of periodic
paralysis and myotonia congenita. All of these diseases are caused by
mutations in genes that code for chloride, sodium, calcium, or potassium
ion channels in the muscle membrane, and they are referred to as ion
channel diseases, or as “channelopathies.” Within
this group there are also instances of muscle conditions that display
no myotonia but only periodic paralysis.
Given that these are disorders of muscle membrane excitability,
it is not surprising that the primary defects are in voltage-dependent
ion channels. By analogy, it was anticipated that ion channelopathies
would be implicated in two other categories of disease in which
there is altered membrane excitability, namely the epilepsies and
certain cardiac arrhythmias and indeed, this has proven to be the
case (see discussion in Chap. 16 on the epilepsies).
In the process, several new forms of nondystrophic myotonia have
been defined. Molecular studies, notably those of Rüdel,
Lehmann-Horn (2004), and Ricker and their associates, identified
the fundamental defects in the myotonias and episodic paralyses
and clarified their relationships. The biology of the ion channels
and their disease-related mutations are reviewed by Hanna and colleagues,
and by Cannon.
Table 54-1 summarizes the main features
of the ion channel diseases affecting muscle and the individual members
of the group are described as follows.
Table 54-1 The Main Inherited
Myotonias and Periodic Paralyses (the Channelopathies) |Favorite Table|Download (.pdf)
Table 54-1 The Main Inherited
Myotonias and Periodic Paralyses (the Channelopathies)
|Disease||Myotonia congenita (Thomsen’s)||Generalized myotonia (Becker)||Hyperkalemic periodic paralysis||Paramyotonia congenita (Eulenburg)||Hypokalemic periodic paralysis||Malignant hyperthermia||Andersen disease|
|Channel protein||CLC1||CLC1||Alpha subunit||Alpha subunit||Dihydropyridine receptor||Ryanodine receptor||Inward rectifying K channel|
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