Early onset or syndromic epilepsy

Gene: WSB2

Green List (high evidence)

Comment on list classification: There are three unrelated patients reported with seizures and with biallelic WSB2 variants. In addition, there is also functional evidence available in support of the association of this gene with the neurodevelopmental disorder. Hence, this gene can be promoted to green rating in the next GMS update.

Created: 2 Jan 2026, 2:12 p.m. | Last Modified: 9 Jan 2026, 1:28 p.m.

Panel Version: 8.88

PMID:40374945 reported five patients from four unrelated families with developmental delays, brain anomalies, and dysmorphic features with or without intrauterine growth restriction (IUGR) and hypotonia. They were all identified with homozygous predicted loss-of-function (pLoF) or missense variants in WSB2 gene (c.128G>A/ p.Trp43Ter, p.Gln134ArgfsTer14, c.1121G>A/ p.Arg374Gln & c.1187_1188delAA/ p.Lys396ArgfsTer19) inherited from asymptomatic consanguineous parents.

Seizures were reported in three of five patients including one of two patients from the Ashkenazi Jew family (child without seizures is aged 9 years old, while the onset of seizure on the other child was at 10 years of age). One of the patients is now free of seizures and not on medication, while the other two patients responded to treatments.

There is also functional evidence available from Wsb2-mutant mice, which exhibited several neurological findings that included hyperactivity, altered exploration, and hyper alertness. They also weighed less, had a lower heart rate, and presented an abnormal retinal blood vessel morphology and vasculature pattern along with decreased total thickness of the retina.

This gene has not been associated with relevant phenotypes either in OMIM, Gene2Phenotype or ClinGen.
Sources: Literature

Created: 2 Jan 2026, 2:04 p.m. | Last Modified: 9 Jan 2026, 1:17 p.m.

Panel Version: 8.88

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
neurodevelopmental disorder, MONDO:0700092

Publications

• 40374945