Affiliations: [a] Center for Gene Therapy, The Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA | [b] Departments of Pediatrics and Neurology, Nationwide Children’s Hospital/The Ohio State University, Columbus, OH, USA | [c] Department of Pathology and Laboratory Medicine, Nationwide Children’s Hospital, Columbus, OH, USA | [d] Division of Anatomy, The Ohio State University, Columbus, OH, USA | [e] The Department of Pathology, The Ohio State University, Columbus, OH, USA | [f] King Chulalongkorn Memorial Hospital and Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
Correspondence to: Megan Waldrop, MD, The Research Institute at Nationwide Children’s Hospital 700 Children’s Drive Rm WA 3013, Ohio, USA. Tel.: +1 614 722 2231; Fax: +1 614 722 3273; E-mail: [email protected]ens.org.
Abstract: Background:The phenotypic spectrum of the skeletal muscle voltage-gated sodium channel gene (SCN4A) mutations has been expanding dramatically with advancements in genetic testing. Previously only known to cause autosomal dominant myotonia or periodic paralysis, now recessive mutations have been found causing congenital myopathies and congenital myasthenic syndromes. Case presentation:A 27-year-old woman who was born with Arnold-Chiari malformation, hydrocephalus, high-arched palate, bilateral hip dysplasia, and severe scoliosis presented for evaluation of episodic muscle stiffness and weakness. Electrodiagnostic studies revealed myopathy and widespread myotonia. Muscle histopathology showed marked fiber size variability, type I fiber predominance with minimal scattered necrosis and regeneration which was typical of a congenital myopathy with an additional finding of a lobulated structural pattern in type I fibers. Sequential individual gene testing revealed a novel de novo heterozygous c.2386 C > G, p.Leu796Val missense mutation in the SCN4A gene. Discussion:To the best of our knowledge, this is the first report of a dominant, heterozygous mutation in SCN4A causing a complex phenotype of congenital myopathy and myotonia with multiple congenital anomalies and unique muscle pathology findings. This case is another addition to the ever expanding phenotype of SCN4A mutations.