Early onset or syndromic epilepsy
Gene: EXOSC3
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
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.
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
Phenotypes for gene: EXOSC3 were changed from Pontocerebellar hypoplasia, type 1B, 614678 to Pontocerebellar hypoplasia, type 1B, OMIM:614678
Source Wessex and West Midlands GLH was added to EXOSC3.
Source NHS GMS was added to EXOSC3.
Zornitza Stark: Seizures are reported in some
Publications for gene: EXOSC3 were set to 25144110; 25149867; 23975261
Gene: exosc3 has been classified as Green List (High Evidence).
Gene: exosc3 has been classified as Green List (High Evidence).
Publications for gene: EXOSC3 were set to
Mode of inheritance for gene: EXOSC3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EXOSC3 were changed from to Pontocerebellar hypoplasia, type 1B, 614678
Expert Review Amber was added to EXOSC3. Panel: Genetic Epilepsy Syndromes
EXOSC3 was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
EXOSC3 was created by Sarah Leigh