A novel PAX2 heterozygous mutation in a male with anterior segment dysgenesis, colobomatous optic nerves and atypical retinal findings: a case report.

Purpose: To describe previously unreported ocular manifestations associated with a de novo PAX2 variant and emphasise their diagnostic significance in PAX2 related disorder.

Methods: A two month old boy underwent comprehensive ocular assessment (cycloplegic refraction, slit lamp biomicroscopy, axial length, and fundus imaging), full field and multifocal electroretinography, high resolution orbital MRI, and renal ultrasonography. Trio whole genome sequencing (WGS) was performed to identify pathogenic variants.

Results: Ophthalmic evaluation revealed asymmetric microcornea (9.5 mm OD, 10.8 mm OS), microphthalmos (axial length 17.1 mm OD, 18.4 mm OS), anterior segment dysgenesis with shallow anterior chambers, and high myopia (12.50 D OD, 10.75 D OS). Fundus photography demonstrated bilateral, steeply excavated optic discs bordered by circumferential peripapillary retinal pigment epithelium agenesis. Multifocal ERG showed markedly reduced central responses, consistent with bilateral macular pathway dysfunction; full field ERG was otherwise within age matched limits. Orbital MRI confirmed fusiform enlargement of the intra orbital optic nerves and colobomatous optic nerve head defects, with anomalous infra orbital optic nerve sheaths. Renal ultrasound was normal. Trio WGS identified a de novo heterozygous PAX2 frameshift variant, c.76dup p.(Val26GlyfsTer28), classified as pathogenic (ACMG criteria PVS1, PS2).

Conclusions: This case expands the phenotypic spectrum of PAX2 related disorder to include anterior segment dysgenesis, axial myopia, peripapillary RPE agenesis, and abnormal infra orbital optic nerve sheaths in the absence of renal hypodysplasia. Recognition of these atypical ocular findings should prompt targeted genetic testing for PAX2, facilitating accurate diagnosis, anticipatory renal surveillance, and informed genetic counselling.