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.