Early onset or syndromic epilepsy

Gene: DHCR7

I don't know

Seizures can occur, but are not more common than in the general population. AR Smith-Lemli-Opitz syndrome (SLOS) - Multiple congenital malformation and mental retardation syndrome. On panel app they mention its association with seizures (OMIM) - which although mentioned in the list of clinical features on OMIM - none of the patients/families describefd in the OMIM entry mention seizures/epilepsy. Schreiber et al, 2014 - examining the prevalence of EEG abnormalities in SLOS in 23 children. Looking at 85 EEGs 43 (51%) were abnormal predominnetly because of interictal epileptiform discharges (IEDs) - equate to 13 subjects, 9 seizure free and only 1 subject had documented clinical seizures. They conclude that epileptiform discharges are common in SLOS despite a relatively low prevalence of epilepsy.

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
Smith-Lemli-Opitz syndrome, 270400

Publications

• 20052364

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: Amber.

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

Panel Version: 1.189

Comment on list classification: Demoted rating from Green to Amber following agreement from Helen Brittain (Genomics England clinical team). DHCR7 is currently Green based on its association with Smith-Lemli-Opitz syndrome (SLOS). Seizures are uncommon (1/23 in PMID:24920862 and 1/3 in PMID:29226552). A 2002 paper (PMID:10807690) also suggests seizures are no more common than in general population. Therefore further evidence is required for a clear link between DHCR7 and seizure phenotype. Note that DHCR7 has been promoted to Green on the metabolism panels so will be Green on the GMS epilepsy superpanel through the metabolic phenotype.

Created: 25 Jul 2019, 3:37 p.m. | Last Modified: 25 Jul 2019, 3:37 p.m.

Panel Version: 1.182

PMID:29226552: Dang Do et al., 2018 report 3 individuals with SLOS- seizures seen in 1 of 3 patients.

Created: 22 Jul 2019, 11:36 a.m. | Last Modified: 22 Jul 2019, 11:36 a.m.

Panel Version: 1.173

PMID:10807690: Kelley et al., 2000 report that seizures are uncommon in biochemically-proven cases of Smith-Lemli-Poitz syndrome (SLOS), and may not be substantially more frequent than in children without SLOS.

Created: 22 Jul 2019, 11:36 a.m. | Last Modified: 22 Jul 2019, 11:36 a.m.

Panel Version: 1.173

PMID:24920862: Schreiber et al., 2014 examined 23 children age 4-17 with Smith-Lemli-Poitz syndrome (SLOS). 1 subject had documented clinical seizures.

Created: 22 Jul 2019, 11:36 a.m. | Last Modified: 22 Jul 2019, 11:36 a.m.

Panel Version: 1.173

Green List (high evidence)

Associated with phenotype (which includes seizures) in OMIM and as confirmed Gen2Phen gene. At least 21 variants reported

Created: 14 Aug 2018, 10:23 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Smith-Lemli-Opitz syndrome 270400