Structural eye disease

Gene: MYH10

I don't know

Comment on list classification: Four of six patients from three unrelated families were reported with monoallelic MYH10 variants and ocular coloboma. In addition, functional evidence from patient fibroblasts and delayed eye development in zebrafish model support the association.

However, this gene should be currently rated amber as coloboma was not consistently reported in all six patents from PMID:40044823 and was entirely absent in the previously reported cohort with neurodevelopmental phenotype (PMID:35980381).

The 'watchlist' tag has been added to review this gene for any new evidence in the future.

Created: 18 Sep 2025, 6:35 p.m. | Last Modified: 18 Sep 2025, 6:35 p.m.

Panel Version: 4.23

PMID:35980381 (2022) reported a cohort of 16 individuals with 14 unique heterozygous MYH10 variants presenting with a broad spectrum of neurodevelopmental disorders. Eye-related phenotypes were relatively minor with ptosis in 3 patients, refractive errors in four and chorioretinal lacunae in one patient.

PMID:40044823 (2025) reported six individuals from three unrelated families presenting with autosomal dominant eye malformations, including ocular coloboma, ptosis and craniofacial features, and identified with 3 novel heterozygous variants (one of missense, splice site and one AA deletion) in the tail domain of MYH10 gene via exome or genome sequencing. However, no neurodevelopmental disorders as usually observed in this syndrome were detected. Iris and choreoretinal coloboma was reported in four of six individuals from three unrelated families (2/3 patients from family 1, 1/2 patients from family 2 and the only patient from family 3). Heterozygous variant in HOXD13 gene was identified in both mother and son from family 2, which was reported to explain their extremities anomalies. In addition, MYH10 dysfunction led to delayed development of the eye and muscular phenotype in the zebrafish model.

This gene has been currently rated Amber on Anophthalmia_Microphthalmia_Coloboma panel (https://panelapp-aus.org/panels/42/gene/MYH10/) in PanelApp Australia based on the evidence from PMID:40044823. This gene has also been rated 'moderate' on the DD panel based on the neurodevelopmental phenotype. However, it has not yet been associated with any relevant phenotypes in OMIM.

Created: 18 Sep 2025, 6:25 p.m. | Last Modified: 18 Sep 2025, 6:26 p.m.

Panel Version: 4.20

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
neurodevelopmental disorder, MONDO:0700092; coloboma, MONDO:0001476

Publications

• 35980381
• 40044823

Green List (high evidence)

PMID: 40044823 reported six individuals from 3 unrelated families presenting with autosomal dominant eye malformations, including ocular coloboma, ptosis and craniofacial features suggesting Baraitser-Winter cerebrofrontofacial syndrome. No neurodevelopmental features.
3 novel heterozygous variants in the MYH10 gene reported.
Sources: Literature

Created: 13 Aug 2025, 10:27 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Autosomal dominant eye malformations, including ocular coloboma, ptosis and craniofacial features

Publications

• PMID: 40044823