Early onset or syndromic epilepsy
Gene: SLC5A6
PMID 35013551 Holling et al, 2022 - reporting 5 individuals from 3 families with motor neuropathies. Hom variant c.1285A>G p.(Ser429Gly) in 3 aff siblings and a simplex patient; and a third family where proband had a mat inherited c.280C>T p.(Arg94*) and a pat inherited c.485A>G p.(Tyr162Cys). in silico tools suggest missense variants affect function. No mention of epilepsy in any of these individuals.
PMID 38036278 Hsieh et al 2023 - Family with compound het SLC5A6 missense variants reported. No mention of epilepsy in affected individuals.
PMID 38012394 Utsuno et al 2024 - 3 sibs from a Japanese family with periventricular brain cysts and motor developmental delay - all compund het for SLC5A6 missense variants - no mention of epilepsy/seizure in any of these sibs.
PMID 37391029 Montomoli et al 2023 - 3 members of the same family - Patient 2 had a generalised tonic-clonic seizre and EEG showed sharp waves in left centro-temporal region. No mention of seizures at follow up at 24 years of age, and no mention prior to this seizure but lots of other clinical features. All affecteds had a hom fs SLC5A6 variant, parents het. Table summarising cases showed epilepsy in 2/13 case - patient 2 in this paper and the Byrne et al paper.
PMID 31754459 Byrne et al - see review 31/01/2021.
No new evidence to support a stronger link with SLC5A6 and an epilepsy phenotype.Created: 7 Feb 2024, 4:22 p.m. | Last Modified: 7 Feb 2024, 4:22 p.m.
Panel Version: 4.163
Byrne et al, 2019 - sibling pair displaying an early infantile-onset, progressive neurodegenerative phenotype with symptoms of dev delay and epileptic encephalopathy, developing from 12-14 months of age - only seen in one of the sibs. Pathogenicity of the identified variants was demonstrated by impaired biotin uptake of mutant SMTV. Idenitification of this disorder guided targeted therepeuitc intervention, resulting clinically in improvement of the patients neurocognitive and neuromotor function. Subramanian et al, 2017 - 2 variants identified in a child by WGS - no mention of epilepsy seen in this individual. Not enough evidence to suggest this gene is associated with epilepsy.Created: 31 Jan 2021, 9 p.m. | Last Modified: 31 Jan 2021, 9 p.m.
Panel Version: 2.281
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
There is insufficient evidence of epilepsy associated with SLC5A6 variants (PMID: 35013551; 38036278; 38012394; 37391029; 31754459) for this gene to be rated as Amber on the Early onset or syndromic epilepsy, therefore it have been demoted to Red.Created: 29 Feb 2024, 2:16 p.m. | Last Modified: 29 Feb 2024, 2:16 p.m.
Panel Version: 4.173
The to_be_confirmed_NHSE tag has been added, as further NHSE review is required.Created: 15 Mar 2022, 3:32 p.m. | Last Modified: 15 Mar 2022, 3:32 p.m.
Panel Version: 2.498
For review tag has been added, to allow for GMS discussion in relation to the metabolic role of this gene. There are insufficient cases with seizures to be green on the Genetic epilepsy syndromes panel.Created: 26 Oct 2020, 3:22 p.m. | Last Modified: 1 Feb 2021, 3:23 p.m.
Panel Version: 2.285
Watchlist tag was added to take account of the potential therapeutic options of this cause of seizures.Created: 8 Jul 2020, 9:40 a.m. | Last Modified: 8 Jul 2020, 9:40 a.m.
Panel Version: 2.113
Comment on list classification: Not associated with phenotype in OMIM and as possible Gen2Phen gene for SLC5A6-related Neurodevelopmental Disorder. At least 4 variants published in two unrelated famililies (3 cases total) with SLC5A6-related Neurodevelopmental Disorder, together with supportive functional studies. One of the cases had mixed semiology seizures including focal dyscognitive, absence, tonic spasms and generalised convulsive seizures with electrographic features of encephalopathy with generalised and independent multifocal spike-wave discharges (PMID 31754459).Created: 2 Jun 2020, 5:31 p.m. | Last Modified: 2 Jun 2020, 5:31 p.m.
Panel Version: 2.85
Two unrelated families reported, functional data and some evidence of response to treatment.
Sources: Expert listCreated: 25 Jan 2020, 6:55 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Developmental delay; epilepsy; neurodegeneration
Publications
Variants in this GENE are reported as part of current diagnostic practice
Publications for gene: SLC5A6 were set to 27904971; 31392107; 31754459; 23104561; 29669219
Gene: slc5a6 has been classified as Red List (Low Evidence).
Tag watchlist was removed from gene: SLC5A6. Tag for-review was removed from gene: SLC5A6. Tag to_be_confirmed_NHSE was removed from gene: SLC5A6.
Phenotypes for gene: SLC5A6 were changed from SLC5A6-related Neurodevelopmental Disorder to Neurodegeneration, infantile-onset, biotin-responsive, OMIM:618973
Tag to_be_confirmed_NHSE tag was added to gene: SLC5A6.
Tag for-review tag was added to gene: SLC5A6.
Tag watchlist tag was added to gene: SLC5A6.
Publications for gene: SLC5A6 were set to 31754459; 27904971
Phenotypes for gene: SLC5A6 were changed from Developmental delay; epilepsy; neurodegeneration to SLC5A6-related Neurodevelopmental Disorder
Gene: slc5a6 has been classified as Amber List (Moderate Evidence).
gene: SLC5A6 was added gene: SLC5A6 was added to Genetic epilepsy syndromes. Sources: Expert list Mode of inheritance for gene: SLC5A6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC5A6 were set to 31754459; 27904971 Phenotypes for gene: SLC5A6 were set to Developmental delay; epilepsy; neurodegeneration Review for gene: SLC5A6 was set to GREEN gene: SLC5A6 was marked as current diagnostic