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. 2019 Jul 1;4(3):498-503.
doi: 10.1002/epi4.12347. eCollection 2019 Sep.

Possible role of SCN4A skeletal muscle mutation in apnea during seizure

Dilşad Türkdoğan  1 , Emma Matthews  2 , Sunay Usluer  3 , Aslı Gündoğdu  4 , Kayıhan Uluç  5 , Roope Mannikko  2 , Michael G Hanna  2 , Sanjay M Sisodiya  6   7 , Hande S Çağlayan  4   8
Affiliations

Possible role of SCN4A skeletal muscle mutation in apnea during seizure

Dilşad Türkdoğan et al. Epilepsia Open. .

Abstract

SCN4A gene mutations cause a number of neuromuscular phenotypes including myotonia. A subset of infants with myotonia-causing mutations experience severe life-threatening episodic laryngospasm with apnea. We have recently identified similar SCN4A mutations in association with sudden infant death syndrome. Laryngospasm has also been proposed as a contributory mechanism to some cases of sudden unexpected death in epilepsy (SUDEP). We report an infant with EEG-confirmed seizures and recurrent apneas. Whole-exome sequencing identified a known pathogenic mutation in the SCN4A gene that has been reported in several unrelated families with myotonic disorder. We propose that the SCN4A mutation contributed to the apneas in our case, irrespective of the underlying cause of the epilepsy. We suggest this supports the notion that laryngospasm may contribute to some cases of SUDEP, and implicates a possible shared mechanism between a proportion of sudden infant deaths and sudden unexpected deaths in epilepsy.

Keywords: SUDEP; laryngospasm; myotonia; sodium channel.

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Conflict of interest statement

EM has received an honorarium for attending an advisory board organized by LUPIN pharmaceuticals. The remaining authors have no conflicts of interest. We confirm that we have read the journal's position on issues involved in ethical publication and confirm that this report is consistent with those guidelines.

Figures

Figure 1
Figure 1
EEG examination at 2 months of age showed repetitive sharp waves at left occipital region (A) and left temporal region (B). EEG examination at 3 months of age showed sharp waves at left frontal (C) and left temporal region (D)
Figure 2
Figure 2
EMG examinations done in the father carrying the SCN4A variant showed increased insertional activity on upper (A) and lower extremity muscles (B) and delayed lower amplitude motor response following the compound motor action potential on median motor NCS (C) and Sanger sequencing results of the SCN4A c.G3466A variant in the family (D)
See this image and copyright information in PMC

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