Analysis of one familial hypokalemic periodic paralysis family with R669H variant of SCN4A gene / 临床神经病学杂志

Objective To investigate the clinical and genetic characteristics of a family with hypokalemic periodic paralysis(HOKPP).Methods The clinical data of one HOKPP family were retrospectively analyzed.Results The proband presented with periodic paralysis,limb weakness and decreased serum potassium(1-2 mmol/L).The proband's father and cousin had similar symptoms.A heterozygous missense variant c.2006G＞A(p.R669H)in SCN4A gene was identified in the proband,his father,younger aunt and cousin using gene detection.However,the variant was absent in his elder aunt and younger uncle.Conclusions The family shows irregular dominant inheritance.The severity,frequency and age of onset of male heterozygotes were different,while female heterozygotes had no clinical phenotype.The study first confirms that the R669H variant in SCN4A gene causes complete penetrance in males and carriers in females in Asian populations.

Physical Therapy Interventions and Response to this Treatment in a 13-year-old Female with Paramyotonia Congenita

Background: Paramyotonia Congenita (PMC) is a rare genetic disorder that affects the sodium ion pump at the level of muscles, retarding muscular relaxation after activation. Symptoms may include isolated or global muscle stiffness, with or without pain. The purpose of this case is to describe physical therapy interventions and response to this treatment in a 13-year-old female with paramyotonia congenita. Case Summary: 13-year-old female diagnosed with Paramyotonia Congenita and a 4-month history of increased low back and bilateral hip pain. Treatment consisted of therapeutic heating modalities, aquatic therapy, and stretches. Patient and family education and coordination for an individual education plan were also implemented.Outcome Measures: The patient was treated at an outpatient clinic for 13 sessions. She showed improvements in shoulder, hip, and back range of motion and pain. Goniometric measurements were used to track the range of motion, and a 0-10 visual analog scale and Wong-baker FACES pain rating scale were used to measure pain.Conclusion: Physical therapy intervention may be an effective treatment option in reducing pain in a 13-year-old girl with PMC. Treatment modalities utilizing heat application may have decreased pain for several days at a time, and deeper heating options appear to yield greater effectiveness at reducing pain for longer periods. However, additional research is needed to evaluate the effectiveness of physical therapy treatment with PMC, including the role and application of deep heat and other treatment modalities.

New phenotype of severe neonatal episodic laryngospasm due to a missense mutation in SCN4A: A case report and literature review / 中南大学学报(医学版)

Severe neonatal episodic laryngospasm (SNEL) is an ion channel disease characterized by recurrent life-threatening myotonia of respiratory muscle due to mutations in the voltage-gated sodium channel genes. Here we reported a newborn manifested as paroxysmal cyanosis and limb myotonia after birth. The neonate also developed muscle hypertrophy and stunted growth during the follow-up. Whole exome sequencing confirmed c.2395G>A, p. Ala799Thr heterozygous mutation of SCN4A. Carbamazepine was found to be effective on treating the disease. This case expands our understanding of the phenotype resulting from SCN4A mutations. By summarizing the characteristics of reported 16 cases in SNEL, we found they were mainly in the p.G1306E mutation. The common symptoms were upper airway muscle stiffness and feeding difficulties during neonates. When grow up, most patients have different degrees of recurrent attacks of myotonia and progressed muscle hypertrophy. Some of them have athlete-like special faces but all showed myotonic discharge in eletromyogram.

A novel in-frame mutation at the boundary between exon 21 and intron 21 of SCN4A in a family with paramyotonia congenita

@#Nondystrophic myotonias and periodic paralyses are an important group of genetic skeletal muscle disorders characterized by dysfunction of ion channels that regulate cell membrane excitability. Mutations in the Sodium Voltage-Gated Channel Alpha Subunit 4 (SCN4A) gene are associated with a spectrum of a heterogeneous group of skeletal muscle such as sodium channel myotonia, paramyotonia congenita, hyperkalemic periodic paralysis, congenital myasthenia, and congenital myopathy. Gain of function mutations in SCN4A cause three muscle disorders with overlapping clinical phenotypes: myotonia, paramyotonia congenita, and hyperkalemic periodic paralysis. Here, we describe the clinical and genetic features of a new family with paramyotonia. The proband, an eight-year-old girl, began to experience muscle stiffness in her hands and limbs on exposure to exercise exercise at the age of four and presented with myotonia. She was initially misdiagnosed with myotonic dystrophy because of worsening weakness with significant elevation of serum creatinine kinase levels. Two other affected family members had paradoxical myotonia in the face and hands on exposure to cold muscle stiffness in her face, hands, and limbs on exposure to cold and showed grip myotonia on physical examination. A novel heterozygous in-frame insertion, c.3911_3912+1dupAGA, at the boundary between exon 21 and intron 21 of SCN4A was identified using whole exome sequencing. Our finding enhances our understanding of the genotype and phenotype of patients with paramyotonia congenita, caused by mutations in the SCN4A gene.

Paramyotonia congenita and hypokalemic periodic paralysis in a family with mutation p.R1448H in α-subunit type Ⅳ of voltage gated sodium channel gene / 中华神经科杂志

Objective Through description of the clinical,electrophysiological,pathological and gene sequencing characteristics of a family diagnosed as paramyotonia congenita and hypokalemic periodic paralysis to broaden the understanding of skeletal muscle channel disease and provide the reference for clinical diagnosis.Methods The clinical manifestation,electromyography,muscle pathology and gene sequencing of a family diagnosed as paramyotonia congenita and hypokalemic periodic paralysis in the First Hospital of Shanxi Medical University in October 2017 were collected.Results The proband represented myotonia and episodic muscle weakness,and the manifestations of different patients of the family were varied,including myotonia,episodic muscle weakness or myotonia and episodic muscle weakness.The electromyography of the proband showed myotonic potential,and the compound muscle action potential decreased by 36％ in 40 minutes after exercise in the long exercise test in cold environment (11 ℃).The gene sequencing showed α-subunit type Ⅳ of voltage gated sodium channel (SCN4A) gene p.R1448H mutation.Conclusions The proband presented with paramyotonia congenita and hypokalemic periodic paralysis.Family clinical manifestations suggested phenotypic heterogeneity.The long exercise text in cold environment (11 ℃) confirmed the diagnosis of the proband as paramyotonia congenita and hypokalemic periodic paralysis.Family gene sequencing showed that the mutation of p.R1448H in SCN4A gene was the pathogenic gene mutation site of paramyotonia congenita and hypokalemic periodic paralysis.