Early onset or syndromic epilepsy

Gene: SPATA5

Added new-gene-name tag, new approved HGNC gene symbol for SPATA5 is AFG2A.

Created: 16 Oct 2023, 6:18 p.m. | Last Modified: 16 Oct 2023, 6:18 p.m.

Panel Version: 4.118

Comment on list classification: The Green review by Helen Lord (September 23rd 2019) supports the existing Green rating of SPATA5.

Created: 26 Sep 2019, 4:08 p.m. | Last Modified: 26 Sep 2019, 4:08 p.m.

Panel Version: 1.341

Green List (high evidence)

AR Epilepsy, learing loss and MR syndrome - Tanaka et al, 2015 (26299366) - 14 children from 10 families with a severe neurodevelopmental disorder characterised by delayed psychomotor development, intellectual disability, microcephaly and seizures. All patients had abnormal EEGs and all but 1 had tonic-clonic, myoclonic and/or absence seizures. All patients found to have hom or compound het variants in SPATA5 by WES. No functional work done. Puusepp et al, 2018 (29343804) - 5 patients from 4 unrelated families - all individuals had tonic clonic, clonic or myoclonic seizures and all 5 had abnormal EEGs. Vriants detected included missense, nonsense and small dels. In table 2 they have a phenotypic overview of all the patients with SPATA5 variants reported in the literature so far including their 5 patients: epilepsy seen in 73% (5/5 (Puusepp 5 patients in 4 families), 13/14 (Tanaka 14 patients in 10 families), 3/3 (Kurata 3 patients in 2 families), 1/8 (Buchert 8 patients in 2 families) and all those in whom EEG's were available were abnormal. Together 25 different variants have been reported across the gene, no mutation hot spots.

Created: 23 Sep 2019, 1:19 p.m. | Last Modified: 23 Sep 2019, 1:19 p.m.

Panel Version: 1.336

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 26299366
• 29343804

Comment on list classification: Based on review from Rachel Jones (GSTT): Tanaka et al PMID: 26299366 identified "14 individuals [from 10 families] with microcephaly, developmental delay, intellectual disability, hypotonia, spasticity, seizures, sensorineural hearing loss, cortical visual impairment, and rare autosomal-recessive predicted pathogenic variants" in SPATA5 Puussep et al PMID: 29343804 describes 5 further patients "with psychomotor developmental delay, microcephaly, epilepsy and hearing impairment, who were thought clinically to have a mitochondrial disease with subsequent whole-exome sequencing analysis detecting compound heterozygous variants in the SPATA5 gene" Szczaluba et al PMID: 28293831 describes a family where a sibling has isolated sensorineural hearing loss and the same two pathogenic SPATA5 variants as her more typically affected sister. In addition, typically affected individuals may present as congenital SNHL on newborn hearing screen prior to onset of seizures, microcephaly and intellectual disability.

Created: 20 Aug 2019, 3:25 p.m. | Last Modified: 20 Aug 2019, 3:25 p.m.

Panel Version: 1.255

Green List (high evidence)

Greater than 15 families have been identified in multiple publications showing that patients with SPATA5 biallelic variants present with intellectual disability, epilepsy, microcephaly and hearing loss. May present as epileptic encephalopathy/epilepsy in the first year of life prior to onset of obvious developmental delay.
Sources: Other

Created: 19 Aug 2019, 3:45 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epilepsy, hearing loss, and mental retardation syndrome 616577

Publications

• PMID: 27246907
• 29343804
• 26299366