title: Severe neonatal non-dystrophic myotonia secondary to a novel mutation of the voltage-gated sodium channel (SCN4A) gene.
abstract: We report on a patient with a severe, rare neonatal form of non-dystrophic myotonia. The patient presented with facial dysmorphism, muscle hypertrophy, severe constipation, psychomotor delay, and frequent cold-induced episodes of myotonia and muscle weakness leading to severe hypoxia and loss of consciousness. Muscle biopsy was non-specific and electromyography revealed intense generalized myotonia. The myotonic episodes improved after introducing oral mexiletine and maintaining room temperature at 28 degrees C. The patient died at 20 months of age following a bronchopulmonary infection. A previously undescribed de novo heterozygous c.3891C > A change, which predicts p.N1297K in the SCN4A gene. Mutations within the voltage-gated sodium channel alpha-subunit gene (SCN4A) have been described in association with several phenotypes including paramyotonia congenita, hyperkalemic or hypokalemic periodic paralysis, and potassium-aggravated myotonias. The cold-sensitive episodes of stiffness followed by weakness suggested the diagnosis of channelopathy in our patient. However, her neonatal onset, the triggering of severe episodes by exposure to modest decreases in temperature, involvement of respiratory muscles with prolonged apnea, early-onset muscle hypertrophy, psychomotor retardation, and fatal outcome are evocative of a distinct clinical subtype. Our observation expands the phenotypic spectrum of sodium channelopathies.
authors.affiliation: Service de Réanimation Pédiatrique et de Médecine Néonatale, Hôpital d'Enfants, CHU, Dijon, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Gay
authors.forename: Delphine
authors.initials: D
authors.lastname: Dupuis
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.forename: Alice
authors.initials: A
authors.lastname: Masurel-Paulet
authors.forename: Marc
authors.initials: M
authors.lastname: Labenne
authors.forename: Marina
authors.initials: M
authors.lastname: Colombani
authors.forename: Pierre
authors.initials: P
authors.lastname: Soichot
authors.forename: Frédéric
authors.initials: F
authors.lastname: Huet
authors.forename: Bernard
authors.initials: B
authors.lastname: Hainque
authors.forename: Damien
authors.initials: D
authors.lastname: Sternberg
authors.forename: Bertrand
authors.initials: B
authors.lastname: Fontaine
authors.forename: Jean-Bernard
authors.initials: JB
authors.lastname: Gouyon
authors.forename: Christel
authors.initials: C
authors.lastname: Thauvin-Robinet
mesh_terms: D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009224:Myotonia Congenita / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D062553:NAV1.4 Voltage-Gated Sodium Channel; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D062553:NAV1.4 Voltage-Gated Sodium Channel; C106251:SCN4A protein, human; D015222:Sodium Channels