Clinical features of patients with mutations in genes for nanophthalmos.

BACKGROUND/AIMS: To distinguish the clinical feature of nanophthalmos (NNO) caused by mutations in protease serine 56 (), membrane-type frizzled-related protein (), myelin regulatory factor () and transmembrane protein 98 () and to evaluate the association between angle-closure glaucoma (ACG) and NNO.

METHODS

Variants in those four genes were identified through exome sequencing/whole genome sequencing data, and bioinformatic analysis was conducted to identify pathogenic/likely pathogenic (P/LP) variants. This observational study comprehensively summarised ophthalmological data of 67 patients with NNO from 63 families. Ocular parameters from 68 eyes without surgical treatment were subjected to further analysis.

RESULTS

Totally, 67 patients from 63 families harboured 57 P/LP variants in the four genes, including 30 in (47.6%), 23 in (36.5%), 5 in (7.9%) and 5 in (7.9%). ACG was present in 79.1% of patients. An analysis of ocular parameters from 68 eyes revealed that shorter axial length (AL), lower vitreous-to-AL ratios and severe foveal hypoplasia were associated with variants in and . Uveal effusion was more common in patients with variants, while retinitis pigmentosa was frequently observed in patients with variants. Patients with variants exhibited the thinnest retinal nerve fibre layer thickness. Patients with variants had an earlier average onset age of glaucoma.

CONCLUSION

Variants in and are the most common genetic cause of NNO. ACG is a severe complication frequently observed in these patients. Earlier onset of ACG is observed in patients with dominant NNO, while foveal hypoplasia is more common in patients with recessive disease. Recognising these features is helpful in clinical care and genetic counselling.