Gender differences in penetrance and phenotype in hypokalemic periodic paralysis

Muscle Nerve. 2013 Jan;47(1):41-5. doi: 10.1002/mus.23460. Epub 2012 Sep 27.


Introduction: Hypokalemic periodic paralysis (HypoPP) is an autosomal dominant skeletal muscle ion channelopathy. Sex hormones are natural ion channel regulators. Different sex hormones have different effects on ion channels. A comparison of the penetrance and phenotype between males and females with HypoPP mutations should aid in proving that sex hormones play different roles in HypoPP and also provide the basis for the development of therapies against HypoPP.

Methods: We identified all mutation carriers in 4 HypoPP families using PCR sequencing techniques. All patients underwent clinical investigation.

Results: There were 8 men and 7 women mutation carriers in the 4 families. Male carriers had 100% penetrance, but female penetrance was only 28.57%. The highest attack frequency was 50-150 times/year for the men, whereas it was 30-50 times/year for the women. The attacks disappeared during pregnancy.

Conclusions: The penetrance and attack frequency were lower in women than in men with HypoPP mutations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Calcium Channels / genetics*
  • Calcium Channels, L-Type
  • Female
  • Gene Frequency*
  • Humans
  • Hypokalemic Periodic Paralysis / genetics*
  • Male
  • Middle Aged
  • Mutation
  • NAV1.4 Voltage-Gated Sodium Channel / genetics*
  • Pedigree
  • Penetrance
  • Phenotype*
  • Sex Characteristics*


  • CACNA1S protein, human
  • Calcium Channels
  • Calcium Channels, L-Type
  • NAV1.4 Voltage-Gated Sodium Channel
  • SCN4A protein, human