Early onset or syndromic epilepsy

Gene: EXOSC3

Green List (high evidence)

Seizures are not frequently reported.AR pontocerebellar hypoplasia type 1B - combination of cerebellar And spinal motor neuron degeneration beginning at birth - seizures seen in some patients. Rudnick-Schoneborn et al, 2003 - 6 patients from 4 families - all had pontocerebellar hypoplasia - all but 1 of the children died within the first yearof life - 1 had epilepsy and 2 had infantile seizures (3/6). None of the other references listed on OMIM incl Wan et al, 2012, Schwabova et al, 2013 mention epilepsy/seizures in patients. Rudnik-Schoneborn et al, 2013 - bialleleic mutations detected in 10/27 families (37%) most common D132A (11/20 individuals 55%). 3/15 patients had epilepsy - is it the same patients reported in 2003 - could all be related the epilepsy patients? Eggens et al (gene review) - seizures mainly reported in individuals who survive beyone infancy and a few instances of infantile spasms are described. Around 25% of those with prolonged survival develop spasticity or epileptic seizures. Eggens et al, 2014 - 12 families (14 patients) with EXOSC3 mutations with PCH subtype 1. 2/14 (unrelated) had seizures as part of phenotype.

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 1B, 614678

Publications

• 24524299

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

Comment on list classification: Updated rating from Amber to Green: Green review by Zornitza plus sufficient unrelated cases (>3) of seizures in patients with EXOSC3 variants from PMIDs:24524299 and 23284067 for inclusion on panel.

Created: 3 Dec 2018, 10:26 a.m.

Rudnik-Schoneborn et al 2013 (PMID:23284067) detected biallelic variants in EXOSC3 in 15 patients (10 of 27 families). Epileptic seizures occurred in 3 patients in 2 families, including absence epilepsy in patient 2-1 and infantile spasms in 2 sisters (5-1 and 5-2).

Created: 3 Dec 2018, 10:25 a.m.

PMID:24524299 (Eggens et al, 2014) summarise 14 patients with the EXOSC3 variants out of a cohort of 99 PCH patients (90 families). Seizures are reported in patients 7-I and Patient 8. Seizures were not recorded in the p.G31A group (6 patients, 5 families).

Created: 29 Nov 2018, 1:20 p.m.

PMID:23883322: states that Epileptic seizures were not noted in any of their patients.

Created: 29 Nov 2018, 1:09 p.m.

PMID:25144110 summary confirms that epileptic seizures are reported in some patients.

Created: 29 Nov 2018, 1:08 p.m.

PMID:25149867 (Halevy et al, 2014): Of the 4 patients, 1 patient had a single atonic seizure age 12 years.

Created: 29 Nov 2018, 1:08 p.m.

Zanni et al (PMID:23975261, Supplementary table) compare clinical features of two affected Bangladeshi siblings with missense variants in EXOSC3, and compares them to D132A-related PCH1 patients. Epilepsy is not recorded for the siblings, but is listed as a feature of D132A-related PCH1 patients (with no further specifics provided).

Created: 29 Nov 2018, 1:08 p.m.

Green List (high evidence)

Seizures are reported in some patients with this brain development disorder.

Created: 13 Aug 2018, 11:50 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pontocerebellar hypoplasia, type 1B, MIM#614678

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