Early onset or syndromic epilepsy

Gene: SEPSECS

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: John Taylor and Helen Lord. Suggested gene rating: Green.

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

Panel Version: 1.189

Green List (high evidence)

AR Pontocerebellar hypoplasia type 2D (PCH2D) - progressive microcephaly, postnantal onset of progressive atrophy of the cerebellum, profound MR, spasticity and variable seizures. Ben-Zeev et al, 2003 - 4 unrelated patients from non-consang families. 2 had seizures. All had hom/compound het variants. Makrythanasis et al, 2014 - 3 sibs of consang Jordanian parents - all had seizures, hom missense variant. Agamy et al, 2010 - functional work on some variants in this gene - showed to abolish enzyme activity.

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
Pontocerebellar hypoplasia type 2D, 613811

Publications

• 27576344

Comment when marking as ready: Associated with phenotype in OMIM and not in Gen2Phen. At least three variants identified in unrelated cases of Pontocerebellar hypoplasia type 2D 613811, however, the majority of published cases of this condition do not include seizures.

Created: 4 Dec 2018, 10:47 a.m.

Comment on publications: No seizures reported in two milder cases of Pontocerebellar hypoplasia type 2D 613811 in PMID: 26888482. SEPSECS variants not reported in the cases that have seizures (21 trios) in PMID: 25590979. PMID: 26805434 case report of pontocerebellar hypoplasia type 2D and optic nerve atrophy, with homozygous SEPSECS variannt, but no seizures.

Created: 4 Dec 2018, 10:38 a.m.

Green List (high evidence)

Seizures are part of the phenotype of this brain development disorder.

Created: 21 Aug 2018, 9:17 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pontocerebellar hypoplasia type 2D, MIM#613811

Publications

• 20920667
• 25044680

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