White matter disorders and cerebral calcification - narrow panel
Gene: ESAM
Comment on list classification: There is sufficient evidence for this gene to be promoted to green rating in the next GMS review.Created: 13 Sep 2023, 8:08 p.m. | Last Modified: 13 Sep 2023, 8:08 p.m.
Panel Version: 5.284
As reviewed by Julia Baptista, PMID:36996813 reported the identification of biallelic ESAM variants in 13 individuals from eight unrelated families, which included four foetuses. All nine live-born individuals had profound global developmental delay/ unspecified intellectual disability, epilepsy, absent or severely delayed speech, varying degrees of spasticity, ventriculomegaly, and ICH/ cerebral calcifications, the latter being also observed in the foetuses.
This gene has been associated with relevant phenotypes in OMIM (MIM #620371), but not yet in Gene2Phenotype.Created: 13 Sep 2023, 8:04 p.m. | Last Modified: 13 Sep 2023, 8:11 p.m.
Panel Version: 5.284
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity, OMIM:620371
Publications
Lecca et al 2023 reported thirteen patients from eight unrelated families with biallelic loss of function variants (nonsense, frameshift, canonical splice site, all predicted to result in a transcript targeted for nonsense-mediated decay). Protein staining assays in one of the brain fetal samples confirmed loss the loss of protein.
The phenotype reported in this cohort is of a severe neurodevelopmental disorder with brain anomalies (calcifications, hydrocephalus, enlarged ventricles, cerebral atrophy, etc), and dysmorphic features.
Sources: Literature, Expert ReviewCreated: 1 Sep 2023, 12:24 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
severe ID; seizures, spasticity
Publications
Tag Q3_23_NHS_review was removed from gene: ESAM.
gene: ESAM was added gene: ESAM was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Amber,Literature,Expert Review Q3_23_promote_green, Q3_23_NHS_review tags were added to gene: ESAM. Mode of inheritance for gene: ESAM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ESAM were set to 36996813 Phenotypes for gene: ESAM were set to Neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity, OMIM:620371