Myotonia

Mutations in C1C-1 lead to myotonia, a muscle stiffness that is associated with a hyperexcitability of the muscle plasma membrane. Thus, the high resting... 

Myotonia is muscle stiffness, in which muscle relaxation after voluntary contraction is impaired. Mutations in several ion channel genes (Cl, Na, Ca, K channels) can cause myotonias, which can sometimes be differentiated clinically (e.g. paramyotonia is cold-sensitive). C1C-1 mutations cause pure myotonia congenita which is not sensitive to temperature. Channel myotonia comes in a recessive (Becker type)... 

Mutations of the NaVl. 4 channel gene cause various types of muscle diseases, including hyperkalemic periodic paralysis, paramyotonia congenita, myotonia fluctuans, acetazolamide-sensitive myotonia. Mutations disiupt inactivation and cause both myotonia (enhanced excitability) and attacks of paralysis (inexcitability resulting from depolarization). 

Metabolic Myopathies Glycogen Storage Disease Disorders of Lipid Metabolism Respiratory Chain Disorders Mitochondrial DNA Abnormalities Myotonias, Periodic Paralyses, and Malignant Hyperpyrexia Myotonias... 

To cover these various disorders in an orderly and comprehensive manner, the following sections are devoted, respectively, to the muscular dystrophies the congenital myopathies the metabolic myopathies the myotonias, periodic paralyses, and malignant hyperpyrexia the neurogenic disorders the inflammatory muscle disorders the endocrine myopathies and the drug-induced and toxic myopathies. 

This group of conditions, in which myotonia (the failure of voluntary muscle to relax following contraction) may be a feature, can now be classified according to the primary molecular defect responsible for the relevant condition. The clinical features of the different conditions within this group can show some significant differences, even among the diseases now known to be due to mutations within the same genes (Table 1). 

Recessive generalized myotonia AR 7q35 Muscle chloride channel... 

The predominant feature of Thomsen s disease is severe myotonia, worse in the cold and early morning than later in the day or in the warmth, unassociated with significant muscle weakness, degeneration, or other severe pathology. Myotonia is particularly common in ocular muscles, and muscles of the arms and legs. Onset is typically during childhood. 

Congenital myotonic dystrophy is a relatively rare condition in which myotonia (defined electrically) is mostly absent in the affected newborn infant, but becomes apparent in the older infant. Histopathology shows a consistent feature of arrested development and maturation of muscle fibers, but there is, currently, no adequate explanation for this phenomenon. Patients with congenital myotonic dystrophy rarely survive without aggressive ventilatory support, and survivors, without exception, are severely multiply handicapped. 

There is no single underlying cause for the myotonia seen in the muscles of myotonic patients. The typical myotonic response is a train of action potentials generated in a muscle fiber in response to a single stimulus. Experimental work has shown that such a response can be generated in normal muscle fibers in which chloride conductance is suppressed, and this may be the cause of the myotonia of Thomsen s disease (see Barchi, 1988 for examples). It is almost certainly not the cause of myotonia in myotonic dystrophy in which there is an associated fall in... 

Malignant hyperthermia Myotonias and masseter spasm Hyperkaliemia... 

Myotonia congenita (MIM 160800) Chloride channel Skeletal muscle... 

Data in part from Ackerman NJ, Clapham DE Ion channels— basic science and clinical disease. N Engl J Med 1997,-336 1575. Other channelopathies include the long QT syndrome (MIM 192500) pseudoaldosteronism (Liddle syndrome, MIM 177200) persistent hyperinsulinemic hypoglycemia of infancy (MIM 601820) hereditary X-linked recessive type II nephrolithiasis of infancy (Dent syndrome, MIM 300009) and generalized myotonia, recessive (Becker disease, MIM 255700). The term "myotonia" signifies any condition in which muscles do not relax after contraction. 

In preliminary experiments the laboratory of Jockusch and coworkers in collaboration with Al-Awqati [32] has used indanyloxyacetic acid (IAA-94, Fig. 2, cf. below) to purify proteins between 30 and 150 kDa, which appear to be responsible for CP-transport and seem to be absent in one form of hereditary myotonia [8]. During the process of editing this review the Jentsch group has succeeded to clone the skeletal muscle CP-channel and yet another CP-channel [125,127]. 

Special risk Use with caution in the presence of cardiac disease, particularly in digitalized patients or in the presence of renal disease, metabolic acidosis, Addison disease, acute dehydration, prolonged or severe diarrhea, familial periodic paralysis, hypoadrenalism, hyperkalemia, hyponatremia, and myotonia congenita. 

Succinylcholine produces muscle fasciculation, which may result in myoglobinuria and postoperative muscle pain. The amount produced depends on the level of physical fitness. Succinylcholine causes contractions of extraocular muscles, posing the danger of transient elevated intraocular pressure. Succinylcholine may produce hyperkalemia in patients with large masses of traumatized or denervated muscle (e.g., spinal cord injury). Denervated muscle is especially sensitive to depolarizing drugs because of the increased number of AChRs on the sarcolemma (denervation supersensitivity). Succinylcholine also causes prolonged contraction of the diseased muscles of patients with myotonia or amyotrophic lateral sclerosis. 

It is used in the treatment of cerebral falciparum malaria and multidrug resistant strains of cerebral malaria. It is also used along with clindamycin in the treatment of babesiosis. It is also effective in myotonia congenita and nocturnal muscle cramps. 

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