Fetal anomalies
Gene: SCN1A

SCN1A (sodium voltage-gated channel alpha subunit 1)
EnsemblGeneIds (GRCh38): ENSG00000144285
EnsemblGeneIds (GRCh37): ENSG00000144285
OMIM: 182389, Gene2Phenotype
SCN1A is in 13 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 3 Mar 2022, 11:19 a.m. | Last Modified: 3 Mar 2022, 11:19 a.m.

Panel Version: 1.836

Comment on list classification: Although it is anticipated that following birth early-onset seizures will likely represent the predominant characteristic of the phenotype, arthrogryposis multiplex congenita may be detected in utero as demonstrated with the cases in PMID:32928894. Therefore, this gene will be flagged for review at the next GMS panel update to assess whether this is sufficient for inclusion on this panel (added 'for-review' tag).
Created: 2 Dec 2020, 3:05 p.m. | Last Modified: 2 Dec 2020, 3:05 p.m.

Panel Version: 1.116

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.

PMID: 29543227 (2018) - Infant presenting with AMC and severe EE, and de novo p.(Ile1347Asn) variant (Supplementary info) which at the time was thought to only partially explain the phenotype, but in light of the recent paper, 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 Dec 2020, 2:55 p.m. | Last Modified: 2 Dec 2020, 2:55 p.m.

Panel Version: 1.115

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Dravet syndrome, OMIM:607208; Arthrogryposis multiplex congenita

Publications

Created: 2 Dec 2020, 2:55 p.m.
Last Modified: 2 Dec 2020, 2:55 p.m.
Panel version: 1.836

Rebecca Foulger (Genomics England curator)

Red List (low evidence)

This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Phenotype is not fetally-relevant. Action taken: Demoted SCN1A gene rating from Green to Red.
Created: 4 Apr 2019, 2:03 p.m.

DDG2P rating in original PAGE list: Confirmed for SCN1A-RELATED SEIZURE DISORDERS
Created: 11 Dec 2018, 9:05 a.m.

Created: 11 Dec 2018, 9:05 a.m.

Panel version: 0.161

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Sources

Expert Review Green
PAGE DD-Gene2Phenotype

Phenotypes

Dravet syndrome, OMIM:607208
Arthrogryposis multiplex congenita

OMIM

182389

Clinvar variants

Variants in SCN1A

Penetrance

None

Publications

Panels with this gene