Early onset or syndromic epilepsy

Gene: DHCR24

I don't know

PMID 21559050 describe a family with desmosterolosis, which includes seizures in the phenotype. Additionally there are a few other variants reported to be associated with desmosterolsis (although it is not clear from the publications whether the patients suffered with seizures)

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
Desmosterolosis, 602398

Publications

• 21559050
• 21671375

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

Added 'watchlist' tag.

Created: 22 Nov 2018, 4:10 p.m.

Comment on list classification: Kept rating as Amber: Confirmed DD-G2P gene for Desmosterolosis but only 2 families reported so far in the literature with seizures as part of the desmosterolosis phenotype: PMIDs:21559050 and 24961299.

Created: 22 Nov 2018, 4:10 p.m.

Epilepsy not reported as part of phenotype in patients from PMID:21671375 (Schaaf et al 2011) and PMID:11519011 (Waterham et al.2001).

Created: 22 Nov 2018, 4:02 p.m.

Dias et al, 2014 (PMID:24961299) report two sisters homozygous for the 571G>A (E191K) DHCR24 variant with syndromic ID and desmosterolosis. Each had transient neonatal seizures. The authors also provide a summary table of 9 patients to-date (2014) with DHCR24 and Desmosterolosis. Only this family and the kindred reported by PMID:21559050 exhibit seizures as part of their phenotype (3 of 9 patients, 2 families).

Created: 22 Nov 2018, 3:53 p.m.

In affected members of a consanguineous Bedouin family with desmosterolosis, Zolotushko et al. (2011, PMID:21559050) identified a homozygous 307C-T transition in DCHR24 (R103C). The phenotype was consistent among affected individuals and included failure to thrive and seizures.

Created: 22 Nov 2018, 3:01 p.m.

Green List (high evidence)

Seizures are a feature of this multi system metabolic disorder.

Created: 12 Aug 2018, 6:37 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Desmosterolosis, MIM#602398

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