Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
권호 표지
DOI QR코드

DOI QR Code

Familial hyperkalemic periodic paralysis caused by a de novo mutation in the sodium channel gene SCN4A

  • Han, Ji-Yeon (Department of Pediatrics, Konyang University College of Medicine) ;
  • Kim, June-Bum (Department of Pediatrics, Konyang University College of Medicine)
  • Received : 2011.04.05
  • Accepted : 2011.07.06
  • Published : 2011.11.15
Download PDF
⟨ Previous Next ⟩

Abstract

Familial hyperkalemic periodic paralysis (HYPP) is an autosomal-dominant channelopathy characterized by transient and recurrent episodes of paralysis with concomitant hyperkalemia. Mutations in the skeletal muscle voltage-gated sodium channel gene $SCN4A$ have been reported to be responsible for this disease. Here, we report the case of a 16-year-old girl with HYPP whose mutational analysis revealed a heterozygous c.2111C>T substitution in the $SCN4A$ gene leading to a Thr704Met mutation in the protein sequence. The parents were clinically unaffected and did not have a mutation in the $SCN4A$ gene. A $de$ $novo$ $SCN4A$ mutation for familial HYPP has not previously been reported. The patient did not respond to acetazolamide, but showed a marked improvement in paralytic symptoms upon treatment with hydrochlorothiazide. The findings in this case indicate that a $de$ $novo$ mutation needs to be considered when an isolated family member is found to have a HYPP phenotype.

Keywords

References

  1. Lehmann-Horn F, Rudel R, Jurkat-Rott K. Non-dystrophic myotonias and periodic paralyses. In: Engel A, Franzini-Armstrong C, editors. Myology: basic and clinical. 3rd ed. New York: McGraw-Hill, 2004:1257-300.
  2. Feero WG, Wang J, Barany F, Zhou J, Todorovic SM, Conwit R, et al. Hyperkalemic periodic paralysis: rapid molecular diagnosis and relationship of genotype to phenotype in 12 families. Neurology 1993; 43:668-73. https://doi.org/10.1212/WNL.43.4.668
  3. Jurkat-Rott K, Lehmann-Horn F. Genotype-phenotype correlation and therapeutic rationale in hyperkalemic periodic paralysis. Neurotherapeutics 2007;4:216-24. https://doi.org/10.1016/j.nurt.2007.02.001
  4. Paternostro-Sluga T, Grim-Stieger M, Posch M, Schuhfried O, Vacariu G, Mittermaier C, et al. Reliability and validity of the Medical Research Council (MRC) scale and a modified scale for testing muscle strength in patients with radial palsy. J Rehabil Med 2008;40:665-71. https://doi.org/10.2340/16501977-0235
  5. Park YH, Kim JB. An atypical phenotype of hypokalemic periodic paralysis caused by a mutation in the sodium channel gene SCN4A. Korean J Pediatr 2010;53:909-12. https://doi.org/10.3345/kjp.2010.53.10.909
  6. Hantai D, Richard P, Koenig J, Eymard B. Congenital myasthenic syndromes. Curr Opin Neurol 2004;17:539-51. https://doi.org/10.1097/00019052-200410000-00004
  7. Ricker K, Böhlen R, Rohkamm R. Different effectiveness of tocainide and hydrochlorothiazide in paramyotonia congenita with hyperkalemic episodic paralysis. Neurology 1983;33:1615-8. https://doi.org/10.1212/WNL.33.12.1615
  8. Brancati F, Valente EM, Davies NP, Sarkozy A, Sweeney MG, LoMonaco M, et al. Severe infantile hyperkalaemic periodic paralysis and paramyotonia congenita: broadening the clinical spectrum associated with the T704M mutation in SCN4A. J Neurol Neurosurg Psychiatry 2003;74:1339-41. https://doi.org/10.1136/jnnp.74.9.1339
  9. Bouhours M, Luce S, Sternberg D, Willer JC, Fontaine B, Tabti N. A1152D mutation of the Na+ channel causes paramyotonia congenita and emphasizes the role of DIII/S4-S5 linker in fast inactivation. J Physiol 2005;565(Pt 2):415-27. https://doi.org/10.1113/jphysiol.2004.081018
  10. Okuda S, Kanda F, Nishimoto K, Sasaki R, Chihara K. Hyperkalemic periodic paralysis and paramyotonia congenita--a novel sodium channel mutation. J Neurol 2001;248:1003-4. https://doi.org/10.1007/s004150170059
  11. Lehmann-Horn F, Jurkat-Rott K. Voltage-gated ion channels and hereditary disease. Physiol Rev 1999;79:1317-72. https://doi.org/10.1152/physrev.1999.79.4.1317
  12. Lehmann-Horn F, Rüdel R. Molecular pathophysiology of voltage-gated ion channels. Rev Physiol Biochem Pharmacol 1996;128:195-268.
  13. Ptacek L. The familial periodic paralyses and nondystrophic myotonias. Am J Med 1998;105:58-70. https://doi.org/10.1016/S0002-9343(98)00123-5
  14. Miller TM, Dias da Silva MR, Miller HA, Kwiecinski H, Mendell JR, Tawil R, et al. Correlating phenotype and genotype in the periodic paralyses. Neurology 2004;63:1647-55. https://doi.org/10.1212/01.WNL.0000143383.91137.00
  15. Kim JB, Kim MH, Lee SJ, Kim DJ, Lee BC. The Genotype and clinical phenotype of Korean patients with familial hypokalemic periodic paralysis. J Korean Med Sci 2007;22:946-51. https://doi.org/10.3346/jkms.2007.22.6.946

Cited by

  1. Treatment and Management of Neuromuscular Channelopathies vol.16, pp.10, 2011, https://doi.org/10.1007/s11940-014-0313-6
  2. Molecular cloning of ion channels in Felis catus that are related to periodic paralyses in man: a contribution to the understanding of the genetic susceptibility to feline neck ventroflexion and par vol.3, pp.9, 2011, https://doi.org/10.1242/bio.20148003
  3. Hyperkalemic Periodic Paralysis: Case Report with a SCNA4 Gene Mutation and Literature Review vol.2020, pp.None, 2020, https://doi.org/10.1155/2020/8843410