Congenital myaesthenic syndrome
Gene: SCN4A
Review and rating from Michael Oldridge (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust), submitted by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group.Created: 30 Apr 2019, 9:30 a.m.
see PanelApp - extra case described (see publication)Created: 29 Apr 2019, 4:33 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Myasthenic syndrome, congenital, 16, 614198; Congenital Myasthenic Syndrome, Recessive; congenital myasthenic syndromes
Publications
Mutations in SCN4A, encoding the Na V 1.4 sodium channel of skeletal muscle, have been identified in patients with a group of related muscular disorders including myotonia, periodic paralysis, myasthenia, and congenital myopathy. Most mutations are missense with gain-of-function defects. Loss-of-function from enhanced inactivation or null alleles is rare and underlies congenital myasthenia [Source: PMID:27048647].Created: 31 Jan 2017, 2:34 p.m.
PMID:27048647 (Wu et al,. 2016) present a mouse model: using an NaV1.4 (SCN4A) knock-out mouse, Wu et al . show that haploinsufficiency gives rise to latent myasthenia, but not periodic paralysis.Created: 31 Jan 2017, 2:33 p.m.
Habbout et al., 2016 (PMID:26659129) present a proband with fatigable muscle weakness characteristic of congenital myasthenic syndrome with acute and reversible attacks, and a novel (loss-of-function) homozygous SCN4A mutation (p.R1454W).Created: 31 Jan 2017, 2:25 p.m.
In a 57-year-old woman, born of consanguineous parents, with CMS16 (OMIM:614198), Arnold et al. (2015, PMID:25707578) identified a homozygous missense mutation in the SCN4A gene (R1457H).Created: 31 Jan 2017, 2:11 p.m.
In a patient with congenital myasthenic syndrome-16 (OMIM:614198) associated with fatigable generalized weakness and recurrent attacks of respiratory and bulbar paralysis since birth, Tsujino et al. (2003, PMID:12766226) identified compound heterozygous variants in the SCN4A gene (V1442E and S246L).Created: 31 Jan 2017, 2:11 p.m.
Phenotypes for gene: SCN4A were changed from Myasthenic syndrome, congenital, 16, 614198; Congenital Myasthenic Syndrome, Recessive; congenital myasthenic syndromes to Myasthenic syndrome, congenital, 16, OMIM:614198
Publications for gene SCN4A were changed from to http://dx.doi.org/10.1016/j.nmd.2015.06.091
Source NHS GMS was added to SCN4A.
Source Wessex and West Midlands GLH was added to SCN4A.
22 February 2017: Reviews were assessed, and panel was revised according to expert review and additional curation.
Phenotypes for SCN4A were set to Myasthenic syndrome, congenital, 16, 614198; Congenital Myasthenic Syndrome, Recessive; congenital myasthenic syndromes;
Phenotypes for SCN4A were set to Myasthenic syndrome, congenital, 16, 614198; Congenital Myasthenic Syndrome, Recessive;
Phenotypes for SCN4A were set to Myasthenic syndrome, congenital, 16, 614198; Congenital Myasthenic Syndrome, Recessive; Hyperkalemic periodic paralysis, type 2, 170500
SCN4A was added to Congenital myaestheniapanel. Sources: Radboud University Medical Center, Nijmegen
SCN4A was added to Congenital myaestheniapanel. Sources: Emory Genetics Laboratory
SCN4A was added to Congenital myaestheniapanel. Sources: Illumina TruGenome Clinical Sequencing Services