Early onset or syndromic epilepsy

Gene: BCORL1

Red List (low evidence)

XL SHUVER syndrome. Schuurs-Hoeijmakers et al, 2013 (24123876) - 2 Dutch brothers born of unrelated patients - no seizures - hemizygous missense variant, mum unaff. Shukla et al, 2019 (30941876) - 5 boys from 3 unrelated families. 2 unrelated boys - neither had seizures. Three brothers from an Indian family - more severe phenotype including early onset seizures. All had hemizygous missense variants. Mothers unaff or mildly aff. HGMD Pro -other missense variants listed - associated with autism/schizophrenia.

Created: 5 Sep 2019, 2:22 p.m. | Last Modified: 5 Sep 2019, 2:22 p.m.

Panel Version: 1.261

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

I don't know

Kept rating as Red based on Red post-Webex review from Helen Lord.

Created: 9 Sep 2019, 10:16 a.m. | Last Modified: 9 Sep 2019, 10:16 a.m.

Panel Version: 1.314

Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene was added to the Genetic epilepsy syndromes panel after the initial panel was reviewed by West Midlands, Oxford and Wessex GLH: this gene was therefore reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.

Created: 5 Sep 2019, 2:26 p.m. | Last Modified: 5 Sep 2019, 2:26 p.m.

Panel Version: 1.262

Added BCORL1 to the Genetic epilepsy syndromes panel as a Red gene based on a 2019 paper by Shukla et al (PMID:30941876) who report 5 males from 3 families with ASD, ID/DD and dysmorphic features. Three siblings (patients 3, 4 and 5) had Seizures (at 1 year, 2 year and 6 months of age, respectively). Patients 1 and 2 did not have seizures but their ID/DD phenotype was less severe than those of the three brothers. Therefore currently only one family and a Red rating.
Sources: Literature

Created: 6 Jun 2019, 10:34 a.m.

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
Intellectual disability and seizures

Publications

• 30941876