Early onset or syndromic epilepsy

Gene: LARGE1

I don't know

Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Amber.

Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.

Panel Version: 1.189

I don't know

Congenital Muscular Dystrophy would be a better panel for this gene.LARGE1 appears to be associated predominantly with congenital muscular dystrophy, although there is some association with Walker-Warburg syndrome which may sometimes be associated with seizures, secondary to the brain abnormalities (e.g. cobblestone lissencephaly which can lead to hydrocephalus)

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies) type A, 613154; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation) type B, 608840

Comment when marking as ready: Seizures are more common features of other dystroglycanopathies, therefore LARGE1 will remain an amber gene as there is not enough evidence to promote it to a green gene currently. I have added the 'watchlist' tag.

Created: 3 Dec 2018, 10:40 a.m.

Comment on list classification: Muscular dystrophy-dystroglycanopathy was confirmed by both OMIM and Gene2Phenotype; however, seizures/epilepsy was not listed as a phenotype for either databases. There is only one reported case of a patient with mutations in LARGE1 who also have seizures (PMID: 24709677). Therefore not enough evidence to promote to green status.

Created: 21 Nov 2018, 10:45 a.m.

Green List (high evidence)

Seizures are part of the phenotype of dystroglycanopathies.

Created: 16 Aug 2018, 11:25 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6, MIM#613154; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 6, MIM#608840

Variants in this GENE are reported as part of current diagnostic practice