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SCN4A (chromosomal locus 17q23-q25, sodium channel gene)

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Gene Reviews Entry
PubMed Search for HyperKPP

Five muscle diseases are linked to human skeletal and cardiac muscle sodium channels: hyperkalemic periodic paralysis (HyperKPP) (Fontaine et al. 1990; Ptácek et al. 1991a), paramyotonia congenita (PMC) (Ptácek et al. 1991b), potassium-aggravated myotonia (PAM) (Lerche et al. 1993; Ptácek et al. 1994), long QT syndrome (Wang et al. 1995b) and Brugada's syndrome (Chen et al. 1998).

Rüdel, Hana, and Lehmann-Horn (1999), identify at least four mutation variants in the SCN4A (sodium channel gene) that have been associated with the classical clinical picture of Hyperkalemic Periodic Paralysis (HyperKPP). As with other types of Periodic Paralysis, HyperKPP is transmitted by autosomal dominant inheritance. Attacks of weakness, according to the literature, usually occur in the morning, lasting from 10 minutes to as long as an hour or more. Attacks of weakness have been reported to last as long as a day or two. Ashcroft (2000) describes the myotonia (muscle stiffness) associated with HyperKPP as resulting from enhanced muscle excitability. According to Ashcroft, HyperKPP is known to “occur spontaneously, but attacks are usually precipitated by exercise, stress, fasting or eating potassium-rich foods.”

Rüdel, et al. report that some patients may experience only a few attacks of weakness in their lifetime, while others have reported near daily attacks of generalized weakness. During attacks of HyperKPP, serum potassium is mildly elevated to the high end of normal (4.5 mEq/l). Ashcroft (2000) describes potassium levels of between 5 and 7 mM, noting that since plasma potassium levels in non affected individuals can rise to as high as 8mM during strenuous exercise, “it seems possible that potassium may also be a precipitating factor in exercise-induced attacks: if this is the case, however, some additional factor must protect the muscle during the activity itself because the attack is only initiated on cessation of exercise.” Rüdel, et al. (1999) also report that rest following exercise, fasting, and the oral intake of potassium are very efficient in precipitating attacks in provocative testing.

Rüdel, et al., also offer the observation that “some patients always show slight signs of myotonia between and at the beginning of attacks; others show signs of paramyotonia, and in a third category myotonic signs are absent.” The additional observation that serum potassium can fall below normal at the end of an attack suggests that to avoid the misdiagnosis of hypokalemic periodic paralysis, interpretation of blood samples taken during this time should be carefully considered and confirmed by follow-up samples taken at the onset or during the initial stages of an attack.

For additional references, also see:

Molecular basis for hyperkalemic periodic paralysis. Brown RH Jr.

Section Last Modified:
12/29/2009 07:38 PT