Early onset or syndromic epilepsy

Gene: ALG14

Green List (high evidence)

In the Kvarnung et al paper the 2 affected siblings presented with severe intellectual disability, epilepsy, behavioural problems and mild dysmorphic features, - splicing variants. Less severe than hom and compound het cases reported by Schorling et al, 2017. Possiblity of missed cases if the phenotype is less severe (doesn't include early severe neurodegeneration with mopathic and myasthenic features).

Created: 27 Jan 2021, 3:34 p.m. | Last Modified: 27 Jan 2021, 3:34 p.m.

Panel Version: 2.274

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
epilepsy; behavioural problems; severe developmental delay; mild dysmorphic features; severe neurodegeneration with myopathic and myasthenic features

Publications

• 28733338
• 30221345

Green List (high evidence)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 3 Mar 2022, 5:34 p.m. | Last Modified: 3 Mar 2022, 5:34 p.m.

Panel Version: 2.491

For-review tag has been added to highlight whether this gene should be green on this panel due to the uncoupling of metabolic genes from Genetic epilepsy syndromes panel.

Created: 2 Feb 2021, 10:27 a.m. | Last Modified: 2 Feb 2021, 10:27 a.m.

Panel Version: 2.287

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review and depending on the policy of inclusion of metabolic genes on this panel.

Created: 9 Jul 2020, 11:57 a.m. | Last Modified: 9 Jul 2020, 11:57 a.m.

Panel Version: 2.115

Associated with Myasthenic syndrome, congenital, 15, without tubular aggregates 616227 in OMIM, but not associated with phenotype in Gen2Phen. At least 6 variants reported in at least 5 cases with varying phenotypes. PMID 23404334 reports compound heterozygous (p.P65L, P.R104*) sibs, who manifested with myasthenic syndromes, but did not have intellectural disability nor seizures and were 62 and 51 years old when reported. PMID 28733338 reports two compound heterozygous (p.D74N, pV141G), (p.D74N, p.R109Q) cases and a homozygous (p.D74N), with early and lethal neurodegeneration with myasthenic and myopathic features, but the cases died before intellectual disability was manifiest. However, seizures were evident in two compound heterozygous families. PMID 30221345 reports a homozygous splicing variant in a case with intellectual disability and seizures. Functional studies were presented showing that this variant resulting in exon skipping, however, this was not completely prenetrant as wild type protein was detected at a low level in the patient.
Sources: Literature

Created: 9 Jul 2020, 11:53 a.m. | Last Modified: 9 Jul 2020, 12:10 p.m.

Panel Version: 2.115

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital myasthenic syndrome; ?Myasthenic syndrome, congenital, 15, without tubular aggregates, 616227

Publications

• 28733338
• 23404334
• 30221345