Early onset or syndromic epilepsy

Gene: VPS36

I don't know

Comment on list classification: Seizures have been reported in 3 families with biallelic VPS36 variants and seizures. However, two of these families harboured the same variant and shared ancestry was seen in haplotype analysis. Hence, this gene can only be rated Amber with the current evidence.

Created: 27 Jul 2026, 9:57 a.m. | Last Modified: 27 Jul 2026, 9:57 a.m.

Panel Version: 9.42

PMID: 42362802 Chaurasia et al., 2026
Family 21 - VPS36 exon2-3 deletion - 3 affected sibs, one deceased (8yrs)
Family 51 - consanguineous parents; VPS36 c.1103G>A, p.Arg368His - 2 affected sibs, died at 15 months and 3 years
Family 52 - consanguineous parents; VPS36 c.1103G>A, p.Arg368His - 2 affected sibs, died at 4 months and 21 months
Family 53 - consanguineous parents; VPS36 c.1103G>A, p.Arg368His - 3 affected sibs, deceased; 2 unaffected sibs not genotyped
Probands confirmed homozygous, unaffected parents heterozygous. Families 51-53 = 2 Pakistani and 1 Saudi Arabian family. F51 and F53 (Pakistani) were found to have common ancestry, but F52 had a different haplotype.
Phenotypic spectrum of 6 genotyped affected individuals: microcephaly (5/6), motor & speech delay (6/6), ID (5/5 assessed), seizures (5/6, not in family 52), spasticity (5/5), CC agenesis (6/6), cerebellar atrophy (4/6), ventriculomegaly (5/5).

PMID: 28600779 Monies et al., 2017
Individual 16W-0233 - Saudi Arabian patient, homozygous for VPS36:NM_001282169:exon14:c.894-2->T - phenotype: Speech delay, intellectual disability.

VPS36 is not yet associated with a disease entity in OMIM, ClinGen, or Gene2Phenotype (resources accessed 27th July 2026).
Sources: Literature

Created: 27 Jul 2026, 9:51 a.m. | Last Modified: 27 Jul 2026, 9:55 a.m.

Panel Version: 9.41

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
neurodevelopmental disorder, MONDO:0700092

Publications

• 28600779
• 42362802