Fetal anomalies
Gene: ESAM

ESAM (endothelial cell adhesion molecule)
EnsemblGeneIds (GRCh38): ENSG00000149564
EnsemblGeneIds (GRCh37): ENSG00000149564
OMIM: 614281, Gene2Phenotype
ESAM is in 5 panels

3 reviews

Natalie Chandler (North Thames GLH)

Green List (high evidence)

Green on other panels including White matter disorder/epilepsy. PMID 36996813 - Thirteen affected individuals, including four fetuses, from eight unrelated families, with homozygous loss-of-function-type variants in ESAM 2 of the variants are frameshifts, 1x nonsense, 1x canonical splice.- Affected individuals have 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 fetuses.- One of the frameshift variant c.115del (p.Arg39Glyfs*33), was detected in six individuals from four unrelated families from the same geographic region in Turkey (southeastern Anatolia), suggesting a founder effect.- The c.451+1G>A variant was detected in three individuals from two independent families with the same ethnic origin (Arab Bedouin). Foetal intracranial hemorrhage in four foetuses from three unrelated families. Dilation of lateral ventricles and hydrocephalus was a feature also observed in all fetuses.
Created: 20 Feb 2025, 9:35 p.m. | Last Modified: 20 Feb 2025, 9:35 p.m.

Panel Version: 5.15

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity, MIM#620371

Publications

Created: 20 Feb 2025, 9:35 p.m.
Last Modified: 20 Feb 2025, 9:35 p.m.
Panel version: 5.15

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Created: 25 Feb 2025, 11:15 a.m. | Last Modified: 25 Feb 2025, 11:15 a.m.

Panel Version: 5.78

This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Created: 20 Feb 2025, 9:40 p.m. | Last Modified: 20 Feb 2025, 9:40 p.m.

Panel Version: 5.16

Comment on list classification: As reviewed by Julia Baptista, PMID:36996813 reported foetal intracranial hemorrhage in four foetuses from three unrelated families. Hence, there is sufficient evidence for this gene to be promoted to green rating in this panel in the next GMS review.
Created: 6 Nov 2023, 3:40 p.m. | Last Modified: 6 Nov 2023, 3:40 p.m.

Panel Version: 3.116

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity, OMIM:620371

Publications

36996813

Created: 6 Nov 2023, 3:35 p.m.
Last Modified: 6 Nov 2023, 3:35 p.m.
Panel version: 5.78

Julia Baptista (South East Genomic Laboratory Hub, Synnovis, King's College Hospital)

Green List (high evidence)

Four fetuses from three unrelated families (different LOF biallelic variants) with fetal intracranial hemorrhage. Fetal brain tissue from one of the affected individuals at 31 weeks' gestational age showed lack of ESAM staining in the capillary endothelial cells, thus confirming loss of ESAM. Another individual had an abnormal prenatal ultrasound and the pregnancy was terminated at 32 weeks' gestation, but no DNA was available to test for the familial variant.
Neurodevelopmental disorder with cerebral calcifications, hydrocephalus, focal white matter lesions, retina anomalies and dysmorphic features.
Sources: Literature
Created: 1 Sep 2023, 10:35 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
intracranial hemorrhage; cerebral anomalies

Publications

PMID: 36996813

Created: 1 Sep 2023, 10:35 a.m.

Panel version: 3.109

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green
NHS GMS

Phenotypes

Neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity, OMIM:620371

OMIM

614281

Clinvar variants

Variants in ESAM

Penetrance

None

Publications

Panels with this gene