Early onset or syndromic epilepsy

Gene: HCCS

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: Red.

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

Panel Version: 1.189

Red List (low evidence)

This gene appears to be predominantly associated with micophthalmia/ocular abnormalities, athough there is a report of an association with MIDAS which can have infantile seizures as a feature, PMID 17033964.

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

Panel Version: 1.188

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Linear skin defects with multiple congenital anomalies, 309801

Publications

• 17033964

Comment when marking as ready: Despite seizures being listed as a common feature in GeneReviews, there is only 1 reported case of epilepsy with with HCCS gene. Therefore, it will remain as an amber gene. I have added the 'watchlist' tag.

Created: 3 Dec 2018, 10:34 a.m.

Comment when marking as ready: 'Linear skin defects with multiple congenital anomalies 1' confirmed in both OMIM and Gene2Phenotype and seizure is listed as a phenotype in both.
Neurological involvement is a feature of this disorder and seizures is listed as one of these in GeneReviews. However, only found one patient with a misssense variant in this gene had seizures (PMID: 17033964). This review (PMID: 30374660) states that seizures are a rare symptom in this disorder but mentions that patients with variants in HCCS has been reported to have seizures, they reference this article (PMID: 24735900). I have checked the article and could not find any mention of seizures or epilepsy.

Created: 14 Nov 2018, 1:43 p.m.

Green List (high evidence)

XLD. Seizures are part of the phenotype of this multi-system disorder.

Created: 15 Aug 2018, 12:37 a.m.

Mode of inheritance
Other

Phenotypes
Linear skin defects with multiple congenital anomalies 1, MIM#309801

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