Arthrogryposis
Gene: SCN4AGene was reassessed in view of review by Zornitza Stark.
Zaharieva et al. 2016 (PMID: 26700687) report on 11 individuals from six unrelated kindreds with congenital myopathy and biallelic variants in SCN4A. In utero-onset limb contractures and/or talipes were identified in the seven most severely affected individuals (from 3 families) who died prematurely or at term - including talipes (6/7), upper limb contractures (5/7), lower limb contractures (4/7). Of the surviving cohort members, postnatal-onset lower limb contractures were noted in only 1/4 individuals, which subsequently resolved with stretching exercises.
In conclusion, contractures may be a feature in the most severely affected cases of SCN4A-related phenotypes. Furthermore, following previous clinical review at GOSH of the same evidence, it was concluded that this gene should be Green on this panel and therefore have maintained the current Green rating.Created: 8 Feb 2021, 1:04 p.m. | Last Modified: 8 Feb 2021, 1:04 p.m.
Panel Version: 3.66
Multiple congenital contractures are not reported in this cohort. Primary feature is severe hypotonia.Created: 12 Jul 2020, 10:09 a.m. | Last Modified: 12 Jul 2020, 10:09 a.m.
Panel Version: 3.11
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
Comment on list classification: Promoted from red to green due to expert input from Emma Clement and Anna Sarkozy (Great Ormand Street Hospital) that this gene should be on the reporting panel (green). Publication provided reports biallelic variants in a cohort of 11 individuals from six unrelated kindreds with congenital myopathy: PMID: 26700687.Created: 21 Jul 2017, 7:43 a.m.
Mutations only reported in 2 individuals with congenital myasthenic syndrome -neither had arthrogryposisCreated: 4 Jan 2017, 12:18 p.m.
Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes
Myasthenic syndrome, congenital, 16 614198
Publications
Phenotypes for gene: SCN4A were changed from Congenital Myasthenic Syndrome, Recessive; Hyperkalemic periodic paralysis, type 2, 170500 to Myasthenic syndrome, congenital, 16, OMIM:614198, Congenital myasthenic syndrome 16, MONDO:0013620
This gene has been classified as Green List (High Evidence).
Publications for SCN4A were set to 12766226; 20301347;26700687
Publications for SCN4A were set to 12766226; 20301347;26700687
16th Jan 2016: This gene panel was extensively revised with the addition of 101 green genes and review by Alice Gardham. Due to this extensive change to the panel, the decision was made to promote it to the next major version, version 2.
This gene has been classified as Red List (Low Evidence).
Publications for SCN4A were set to 12766226; 20301347
This gene has been classified as Red List (Low Evidence).
SCN4A was created by ellenmcdonagh
SCN4A was added to Arthrogryposispanel. Sources: Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen