Severe neonatal non-dystrophic myotonia secondary to a novel mutation of the voltage-gated sodium channel (SCN4A) gene

Autor: Sébastien Gay, Delphine Dupuis, Laurence Faivre, Alice Masurel-Paulet, Marc Labenne, Marina Colombani, Pierre Soichot, Frédéric Huet, Bernard Hainque, Damien Sternberg, Bertrand Fontaine, Jean-Bernard Gouyon, Christel Thauvin-Robinet
Rok vydání: 2008
Předmět:
Zdroj: American Journal of Medical Genetics Part A. :380-383
ISSN: 1552-4833
1552-4825
DOI: 10.1002/ajmg.a.32141
Popis: 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°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. © 2008 Wiley-Liss, Inc.
Databáze: OpenAIRE
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