SCN4A p.R675Q Mutation Leading to Normokalemic Periodic Paralysis: A Family Report and Literature Review

Abstract

Objective: To investigate the clinical features, skeletal muscle imaging, and muscle pathological characteristics of normokalemic periodic paralysis (NormoKPP) caused by mutation of SCN4A gene p.R675Q.Methods: The clinical data, skeletal muscle imaging, pathological data, and gene test results of a family with NormoKPP were collected in detail in October 2018. The previous literature was reviewed and used for comparative analysis.Results: The proband was a 28-year-old male with paroxysmal weakness of both lower limbs for 14 years. Limb weakness was mainly manifested in the proximal extremities of both lower limbs, which occurred two to three times a year. The muscle weakness of each attack lasted for 1–2 weeks and gradually recovered. The blood potassium levels were normal. The abnormal signals of the posterior thigh muscle group and the medial calf muscle group could be seen on the magnetic resonance imaging (MRI) of the skeletal muscle, and the target-fiber could be seen in some muscle fibers in muscle pathology. The father of the proband and his brother had the same symptoms. In the same family, 10 people received genetic testing. The results showed that five had a mutation of SCN4A gene p.R675Q. The mutation gene came from the father of the proband.Conclusion: NormoKPP is a clinically rare form of sodium ion channel disease. The clinical manifestations, skeletal muscle imaging, and pathological changes are different from the common hypokalemic periodic paralysis. SCN4A gene detection is an important means for the diagnosis of NormoKPP.

Ageing contributes to phenotype transition in a mouse model of periodic paralysis

“…If present, muscle biopsies to specifically look for core pathology should be considered. Structural pathology consistent with cores in our opinion (originally reported as target lesions) has been reported in one kindred with normokalaemic PP, which is believed to be within the spectrum of HyperPP 52,53 . However, they have not been a common finding in PP.…”

“…However, they have not been a common finding in PP. In this case, the gastrocnemius was biopsied, and the biopsy was taken after a very prolonged attack after which the patient had not fully recovered force 53 . Gastrocnemius is one of the most commonly and severely affected muscles on MRI of HyperPP patients 54 .…”

“…Structural pathology consistent with cores in our opinion (originally reported as target lesions) has been reported in one kindred with normokalaemic PP, which is believed to be within the spectrum of HyperPP. 52 , 53 However, they have not been a common finding in PP. In this case, the gastrocnemius was biopsied, and the biopsy was taken after a very prolonged attack after which the patient had not fully recovered force.…”

“…In this case, the gastrocnemius was biopsied, and the biopsy was taken after a very prolonged attack after which the patient had not fully recovered force. 53 Gastrocnemius is one of the most commonly and severely affected muscles on MRI of HyperPP patients. 54 However, our clinical practice, as for many other centres in Europe and the United States, is to perform biopsies of quadriceps, deltoids or biceps.…”

The clinical and genetic heterogeneity analysis of five families with primary periodic paralysis

“…The depolarization of sarcolemma leads to inactivation of Na V 1.4 channels to cause periodic paralysis [29,30]. It has been reported that R675Q mutation can cause HypoPP2 in Chinese patients [6], but this mutation is more common in NormoPP [8,9] and can also be seen in HyperPP [31]. T704M mutation in the S5 segment of domain II can result in impaired fast or slow inactivation of Na V 1.4 channel, and, therefore, persistent increased sodium current and sarcolemmal depolarization, which can result in the symptom of paralysis [32,33].…”