Genotype and Phenotype Analysis of Patients With Sporadic Periodic Paralysis

Abstract Introduction 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. Conclusion 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.