Arthrogryposis
Gene: SCN1AThe rating of this gene has been updated following NHS Genomic Medicine Service approvalCreated: 3 Mar 2022, 3:49 p.m. | Last Modified: 3 Mar 2022, 3:49 p.m.
Panel Version: 3.150
Note we have reported this association previously in PMID 29543227 (Supplementary info) in an infant presenting with AMC and severe EE, and de novo p.(Ile1347Asn) variant which at the time was thought to only partially explain the phenotype, but in light of this new report, likely fully explains the phenotype. Given the presence of severe seizure disorder in the two infants who were phenotyped in the newborn period, this likely represents the severe end of the spectrum of SCN1A-related disorders rather than a distinct association.Created: 2 Oct 2020, 10:17 p.m. | Last Modified: 2 Oct 2020, 10:17 p.m.
Panel Version: 3.13
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Arthrogryposis multiplex congenita; Dravet syndrome, MIM# 607208
Publications
Comment on list classification: There are sufficient unrelated cases (4) reported in 2 papers (PMIDs: 32928894 and 29543227) with ACM and variants in this gene.
It is anticipated that early-onset seizures likely represent the predominant feature of the disease presentation (already Green on the Genetic epilepsy syndromes panel), however this gene will be flagged for review to assess whether inclusion on this panel is likely to be of clinical benefit.Created: 2 Dec 2020, 2:44 p.m. | Last Modified: 2 Dec 2020, 2:44 p.m.
Panel Version: 3.18
Note SCN1A is a well-established cause of Dravet syndrome, MIM# 607208Created: 2 Oct 2020, 4:09 p.m. | Last Modified: 2 Oct 2020, 4:09 p.m.
Panel Version: 3.13
Comment on list classification: Association with this phenotype currently based on a single publication, although reporting 3 unrelated cases.
Rating Amber, awaiting further publications/clinical evidence to validate this gene-disease relationship.Created: 2 Oct 2020, 4:05 p.m. | Last Modified: 2 Oct 2020, 4:05 p.m.
Panel Version: 3.13
PMID: 32928894 (2020) - De novo missense variants in SCN1A (p.Leu893Phe, p.Ala989Thr, p.Ile236Thr) were identified in three unrelated patients with AMC which was diagnosed from the second trimester of pregnancy. One patient developed intractable epilepsy from birth and died at 21 days, while the other two pregnancies were terminated. No functional studies of the variants or patient cells were performed.
Sources: LiteratureCreated: 2 Oct 2020, 4 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Arthrogryposis multiplex congenita
Publications
Tag for-review was removed from gene: SCN1A.
Source Expert Review Green was added to SCN1A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: scn1a has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: SCN1A were changed from Arthrogryposis multiplex congenita to Arthrogryposis multiplex congenita; Dravet syndrome, OMIM:607208
Publications for gene: SCN1A were set to 32928894
Tag for-review tag was added to gene: SCN1A.
Gene: scn1a has been classified as Amber List (Moderate Evidence).
gene: SCN1A was added gene: SCN1A was added to Arthrogryposis. Sources: Literature Mode of inheritance for gene: SCN1A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SCN1A were set to 32928894 Phenotypes for gene: SCN1A were set to Arthrogryposis multiplex congenita Review for gene: SCN1A was set to AMBER