Severe microcephaly

Gene: SNW1

Green List (high evidence)

Comment on list classification: As there is sufficient evidence available for the association of this gene with severe microcephaly, it should be promoted to green rating in the next GMS update.

Created: 24 Jul 2026, 6:01 p.m. | Last Modified: 24 Jul 2026, 6:01 p.m.

Panel Version: 9.11

PMID:40608414 (2025) reported the identification of nine different heterozygous variants in nine unrelated patients presenting with a neurodevelopmental disorder with features of moderate to severe intellectual disability (moderate in three, profound in one and severe in four), severe microcephaly (8 of 9), seizures (7 of 9), brain malformations (corpus callosum hypoplasia in 4 individuals and Dandy-Walker malformation in another 2), and facial dysmorphisms (7 of 9). Pregnancy was medically terminated in one case (individual 7) and hence brain malformation and facial dysmorphism were the only reported features among the ones listed above.

Variants were confirmed as de novo in eight individuals, whereas inheritance could not be tested in one due to adoption. The variants included missense (2), splice site (3), in-frame deletions (3), frameshift (1) and start loss (1).

There is also functional evidence available from in vitro studies, and Drosophila and human embryonic stem cell-derived cerebral organoids models. Knockdown of the SNW1 ortholog Bx42 in Drosophila impaired CNS development, marked by reduced brain lobe size and loss of NSC proliferation, and these phenotypes were rescued by reintroduction of human SNW1, indicating conserved function. In cerebral organoids, SNW1 haploinsufficiency recapitulated the microcephaly phenotype, characterised by impaired neural progenitor proliferation and increased apoptosis.

This gene has not yet been associated with relevant phenotypes in OMIM (last accessed 24 July 2026), Gene2Phenotype or ClinGen, but rated green on appropriate panels in PanelApp Australia.
Sources: Literature

Created: 24 Jul 2026, 5:57 p.m. | Last Modified: 24 Jul 2026, 5:59 p.m.

Panel Version: 9.10

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
neurodevelopmental disorder, MONDO:0700092; microcephaly, MONDO:0001149

Publications

• 40608414