title: Genotype and phenotype analysis of patients with sporadic periodic paralysis.
abstract: BACKGROUND
  Sporadic periodic paralysis (SPP), the second leading cause of hypokalemic periodic paralysis (HPP) in Asia, has a presentation similar to that of familial periodic paralysis (FPP) and is caused by gene mutations in the calcium (Ca(2+)) (CACNA1S) and sodium (Na(+)) (SCN4A) channels of skeletal muscle. The authors determined whether SPP shares similar genotype and phenotype with FPP.
  
  
  METHODS
  Sixty SPP patients who did not have a family history of paralysis, abnormal thyroid function tests and other identifiable causes of HPP, and 8 FPP patients were enrolled. Genomic DNA was isolated from blood leukocytes of all SPP and FPP patients. Genetic analysis of whole S4 segment in CACNA1S and SCN4A was performed. Phenotypic analysis included clinical presentations, laboratory data and precipitating events.
  
  
  RESULTS
  All FPP patients had mutations in either CACNA1S or SCN4A, but only 4 SPP patients had de novo mutations in CACNA1S (R1239H) and SCN4A (R669×2, R1135H). SPP patients with de novo mutations manifested a phenotype indistinguishable from that of FPP patients except a later age of onset. SPP patients without mutations also had a later age of onset, significantly fewer attacks of paralysis than FPP patients, and unidentifiable precipitating factors.
  
  
  CONCLUSIONS
  A minority of SPP patients had de novo CACNA1S or SCN4A mutations and may have a variant of FPP. The majority of SPP patients, those without mutations in CACNA1S and SCN4A, represent a unique subgroup of HPP patients, and this form of SPP usually manifests at a later age, is associated with fewer attacks and lacks apparent triggering factors.
authors.affiliation: Division of Nephrology, Departments of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chih-Chien
authors.initials: CC
authors.lastname: Sung
authors.forename: Chih-Jen
authors.initials: CJ
authors.lastname: Cheng
authors.forename: Yi-Fen
authors.initials: YF
authors.lastname: Lo
authors.forename: Mei-Shan
authors.initials: MS
authors.lastname: Lin
authors.forename: Sung-Sen
authors.initials: SS
authors.lastname: Yang
authors.forename: Yu-Chuan
authors.initials: YC
authors.lastname: Hsu
authors.forename: Shih-Hua
authors.initials: SH
authors.lastname: Lin
mesh_terms: D000293:Adolescent; D000328:Adult; D015220:Calcium Channels / Q000235:genetics*; D020746:Calcium Channels, L-Type; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006801:Humans; D020514:Hypokalemic Periodic Paralysis / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D062553:NAV1.4 Voltage-Gated Sodium Channel; D010245:Paralyses, Familial Periodic / Q000175:diagnosis / Q000235:genetics; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics*; D055815:Young Adult
chemical_list: C412223:CACNA1S protein, human; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D062553:NAV1.4 Voltage-Gated Sodium Channel; C106251:SCN4A protein, human; D015222:Sodium Channels