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A muscular channelopathy presenting with a pure myotonia dramatically aggravated by potassium ingestion, with variable cold sensitivity and no episodic weakness. This group includes three forms: myotonia fluctuans, myotonia permanens, and acetazolamide-responsive myotonia.
ORPHA:612Classification level: Group of disorders
These diseases are very rare and their prevalence is unknown.
Myotonia develops during childhood or adolescence and is, by definition, aggravated by potassium ingestion. Cold sensitivity is not systematic but when present, it can be of varying severity. Myotonia is rarely associated with attacks of weakness. Some patients describe a warm-up phenomenon while others report an exacerbation with exercise. Myalgias and cramps are frequent. Intensity and topography of myotonic symptoms may vary. In myotonia fluctuans, episodes of stiffness vary in severity and frequency, and occur during the resting period following exercise. In myotonia permanens, myotonia is continuous and severe and can significantly impair respiration. In acetazolamide-responsive myotonia, stiffness is often painful and myotonia is triggered by fasting and mildly by exercise and cold exposure.
PAM is a sodium muscle channelopathy due to missense mutations of the SCN4A gene encoding the alpha subunit of the skeletal muscle voltage-gated sodium channel Nav1.4.
Diagnosis is based on clinical history, physical exam, electromyographic (EMG) and genetic tests. EMG features comprise myotonic discharges and normal responses to the provocative tests (repeated short exercise tests with and without cooling). CPK levels vary depending on myotonia severity.
Differential diagnoses include myotonia congenita (see this term), and cold sensitive myotonias such as paramyotonia congenita and hyperkalemic periodic paralysis with paramyotonia.
Transmission is autosomal dominant. Genetic counseling should be offered to affected families informing them of the 50% risk that the child of an affected parent has of inheriting the disease-causing mutation.
Management and treatment
Management of patients consists in medical therapy and avoidance of triggering factors (such as potassium-rich food). Mexiletine or carbamazepine is the treatment of choice except in acetazolamide-responsive myotonia where symptoms dramatically improve with acetazolamide. Physical therapy management with massages and stretching may be useful for pain and retractions. In each condition, close monitoring is necessary during surgery. Depolarizing agents can cause severe ventilation problems due to a paradoxical increase of stiffness in respiratory muscles and must be avoided.
Prognosis is good with stability of symptoms during life but respiratory function may be compromised in severe myotonia permanens.
A summary on this disease is available in Deutsch (2010) Español (2010) Français (2010) Italiano (2010) Nederlands (2010) Português (2010) Polski (2010, pdf)
- Clinical practice guidelines
- Deutsch (2012) - AWMF
: produced/endorsed by FSMR(s)