Arthrogryposis

Gene: SCN1A

Green List (high evidence)

Note SCN1A is a well-established cause of Dravet syndrome, MIM# 607208
-----
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.

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 phenotype in the newborn period, this likely represents the severe end of the spectrum of SCN1A-related disorders rather than a distinct association.
Sources: Literature

Created: 2 Oct 2020, 10:14 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Dravet syndrome, MIM# 607208; Arthrogryposis multiplex congenita

Publications

• 32928894
• 29543227