Recurrent episodic apnoea
Gene: SCN4A
The rating of this gene has been set to Green following NHS Genomic Medicine Service approval.Created: 1 Feb 2023, 2:43 p.m. | Last Modified: 1 Feb 2023, 2:43 p.m.
Panel Version: 0.91
Comment on classification: This gene should be rated GREEN as it is implicated in apnoea from at least six unrelated cases with autosomal dominant (AD) inheritance.
All three unrelated male neonates identified with heterozygous variants in SCN4A (p.Gly1306Glu in two unrelated cases and p.Ala799Ser in the third case) that initially displayed episodic laryngospasms, with face and limb myotonia appearing later were reported with episodic apnoea. Two patients survived their respiratory attacks and were efficiently treated by sodium channel blockers (mexiletine, carbamazepine) following diagnosis of myotonia (PMID:20713951). Similarly, an infant with a de novo variant in SCN4A was presented with neonatal onset of severe muscle stiffness with involvement of facial and eyelid muscles, and life-threatening events with respiratory failure due to severe apnoea and thorax rigidity. This boy dramatically improved in both respiratory and motor function under carbamazepine therapy (PMID:31732390). PMID:31440732 also reported an infant with EG-confirmed seizures and recurrent apnoeas.
Proband C from PMID:32509969 identified with heterozygous variant in SCN4A (c.3917G>A (p.G1306E)) was reported with myotonia had recurrent episodes of apnoea when he was five days old. Episodes of laryngospasm significantly reduced with acetazolamide treatment in this patient.
This gene has been associated with relevant phenotypes in both OMIM and G2P. Of phenotypes in OMIM, Myotonia congenita, atypical, acetazolamide-responsive (MIM #608390) that was caused by AD inheritance had patients presenting with apnoea. Only one patient reported with myasthenic syndrome, congenital, 16 (MIM #614198), which was caused by autosomal recessive (AR) inheritance also displayed apnoea. As it was only one case with AR, MONOALLELIC was chosen as mode of inheritance.Created: 3 Jan 2023, 9:05 p.m. | Last Modified: 3 Jan 2023, 9:05 p.m.
Panel Version: 0.85
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Myotonia congenita, atypical, acetazolamide-responsive, OMIM:608390; Myasthenic syndrome, congenital, 16, OMIM:614198
Publications
Gene added on recommendation of Dr Emma Matthews.Created: 21 Dec 2022, 2:49 p.m. | Last Modified: 21 Dec 2022, 2:49 p.m.
Panel Version: 0.2
Phenotypes for gene: SCN4A were changed from to Myotonia congenita, atypical, acetazolamide-responsive, OMIM:608390; Myasthenic syndrome, congenital, 16, OMIM:614198
Publications for gene: SCN4A were set to
Mode of inheritance for gene: SCN4A was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Gene: scn4a has been classified as Green List (High Evidence).
gene: SCN4A was added gene: SCN4A was added to Reccurent episodic apnoea. Sources: Expert list Mode of inheritance for gene: SCN4A was set to