Sodium channel myotonias are inherited muscle diseases that are caused by variants in SCN4A, which include a diverse group of muscle channelopathies with marked genotypic and phenotypic variability. Although rarely reported, there have been cases linking specific SCN4A genotypes to a severe neonatal phenotype- myotonia permanens with SNEL (severe neonatal episodic laryngospasm) onset. SNEL is characterized by hypotonia and recurrent episodes of laryngospasm, followed by severe episodic apneic attacks requiring close respiratory monitoring, or even hospitalization. There is limited literature on the neonatal forms of SNEL, but there have been increased incidences albeit small case reports linked to variants in SCN4A, specifically the G1306E variant.
We report on two siblings and their affected father who harbor the G1306E variant associated with myotonia permanens. The father and children all presented with severe laryngospasms, episodic apneic attacks, cyanosis, and respiratory distress requiring hospitalization during the early neonatal period. The father was started on Quinidine around 12 years of age with near resolution of symptoms but was eventually discontinued due to off-label use. He continues to have laryngospasms, muscle stiffening and cramping, and reduced endurance and fatigue into adulthood. He trialed Phenytoin, Acetazolamide, and Ranolazine with minimal response. The older sibling was started on Oxcarbazepine at 2 months of age with initial positive response but due to persistent symptoms, she was started on Mexiletine with little improvement. After switching to Acetazolamide and Flecainide, she experienced a reduction in muscle stiffness and laryngospasms. The younger sibling was started on Trileptal, Acetazolamide and Flecainide shortly after birth due to early laryngospasms and stiffening evident in the early neonatal period. However, in both cases, while there has been favorable response to treatments, they continue to have symptoms.
In both affected father and children, the diagnostic sequence was similar with some therapeutic response to sodium channel blockers. Neonatal onset episodic laryngospasm may lead to a higher risk for morbidity or mortality, and therefore early recognition and diagnosis of SCN4A-related neonatal disorders is essential both for supportive care, monitoring, and treatments aimed to reduce laryngospasm and improve patient clinical outcome.