title: Mutations in SCN4A: a rare but treatable cause of recurrent life-threatening laryngospasm.
abstract: Laryngospasm is a rare but potentially life-threatening occurrence in infants and usually has infective, allergic, metabolic, or anatomic causes. Underlying genetic conditions are rarely considered. Mutations in SCN4A encoding the voltage-gated sodium channel NaV1.4 have been implicated in a wide spectrum of neuromuscular disorders with variable onset, ranging from a rare form of congenital myasthenic syndrome to both hypokalemic and hyperkalemic forms of periodic paralysis and paramyotonia congenita. Here we report on 3 unrelated patients without family history presenting with recurrent, life-threatening episodes of laryngospasm from the first months of life. Clinical features more typically associated with SCN4A-related disorders such as generalized muscle hypertrophy with clinical or electrical myotonia evolved later in life. All patients were found to be heterozygous for the same SCN4A mutation, c.3917G>A; p.Gly1306Glu. Treatment with carbamazepine resulted in complete abolition of recurrent laryngospasm and alleviated symptoms associated with myotonia and muscle stiffness. We conclude that SCN4A mutations ought to be considered in the differential diagnosis of recurrent infantile laryngospasm because timely institution of treatment can be life-saving.
authors.affiliation: Departments of Paediatric Neurology, Neuromuscular Service, Evelina's Children Hospital, and.
authors.forename: Rahul R
authors.initials: RR
authors.lastname: Singh
authors.affiliation: Neurology & Neurophysiology, Guy's & St Thomas' Hospital NHS Foundation Trust, London, United Kingdom;
authors.forename: S Veronica
authors.initials: SV
authors.lastname: Tan
authors.affiliation: MRC Centre for Neuromuscular Disease and National Hospital for Neurology and Neurosurgery, Queen's Square, London, United Kingdom;
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hanna
authors.affiliation: Dubowitz Neuromuscular Centre, Institute of Child Health and Great Ormond Street Hospital for Children, London, United Kingdom;
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Robb
authors.affiliation: Department of Paediatric Neurology, St George's Hospital, London, United Kingdom; and.
authors.forename: Antonia
authors.initials: A
authors.lastname: Clarke
authors.affiliation: Departments of Paediatric Neurology, Neuromuscular Service, Evelina's Children Hospital, and Randall Division for Cell and Molecular Biophysics, Muscle Signalling Section, and Clinical Neuroscience Division, IOP, King's College, London, United Kingdom heinz.jungbluth@gstt.nhs.uk.
authors.forename: Heinz
authors.initials: H
authors.lastname: Jungbluth
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007826:Laryngismus / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D009154:Mutation / Q000235:genetics*; D062553:NAV1.4 Voltage-Gated Sodium Channel / Q000235:genetics*; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D062553:NAV1.4 Voltage-Gated Sodium Channel; C106251:SCN4A protein, human
keywords: genetics; infant; laryngospasm; myotonia