Three male neonates with episodic laryngospasms responsive to sodium channel blockers are reported by researchers at centres in Lyon, Paris and Rennes, France. Patient 1 was admitted to an ICU at 16 days for acute life-threatening laryngospasm associated with generalized stiffness, cyanosis, and bradycardia, without loss of consciousness or startle reaction, and lasting a few minutes. Exam was normal between attacks, but repeated episodes of apnea with larngospasm, unresponsive to clonazepam or levodopa, required tracheostomy at 3 months. EMG revealed intense generalized myotonia, and at 6 months the infant had developed marked muscular hypertonia. Sequencing the SCN4A gene showed a novel heterozygous mutation. Laryngospasm was controlled with oral carbamazepine (40 mg/kg/day), tracheostomy was removed at 14 months, and psychomotor development and growth were normal by 18 months of age. Patient 2 was admitted with daily episodic apneas at 3 days and intermittent stridor by 2 months. An athletic appearance developed by 7 months, and EMG showed continuous myotonia, exacerbated by cold food and winter. SCN4A analysis showed the same mutation as patient 1. Laryngospasm was controlled with mexiletine, and he could walk at 16 months. Patient 3 had immediate respiratory distress at birth, episodic stridor with apnea, and hypertonia. Spasms occurred with laryngeal endoscopy, and the patient died at 10 days. SCN4A gene sequencing showed a heterozygous de novo mutation. Gene analysis in the parents of all 3 patients was negative for SCN4A mutation. [1]

COMMENT. Severe neonatal episodic laryngospasm is reported as a new phenotype, associated with de novo mutations in the muscular channel gene SCN4A and myotonia responsive to sodium channel blockers. Nondystrophic myotonias related to mutations in the SCN4A gene include myotonia congenita (Thomsen disease), paramyotonia, and sodium channel myotonias (SCM).