Ophthalmic phenotype and strabismus surgery in Angelman syndrome: genotype-specific risks and uniform surgical...

Ophthalmic manifestations in Angelman syndrome (AS)-particularly strabismus surgical outcomes and genotype-phenotype correlations-remain inadequately characterized due to limited cohort sizes in prior studies.

This 6-year (2018-2024) retrospective cohort study analyzed 40 genetically confirmed AS patients undergoing strabismus surgery, stratified by molecular subtype: deletion (15q11.2-q13del [n = 27]) and nondeletion (UBE3A mutations/UPD15pat/imprinting defects [n = 13]). Outcomes included refractive errors, iris hypopigmentation (novel grading on a scale of 0-4 adapted from albinism criteria), and surgical efficacy.

High astigmatism (≥2.00 DC) was significantly more prevalent in deletion patients (54% vs 19% [P = 0.004]). High myopia (> -6.00 D) occurred exclusively in deletion patients (n = 2). Severe iris hypopigmentation (grades 3-4) was unique to the deletion subgroup (33% vs. 0%; P = 0.013), linked to OCA2 codeletion. Surgical success (exodeviation ≤8^Δ/esodeviation ≤5^Δ at 1 year) was comparable (70% vs 77%; P > 0.05), with minimal exodrift (deletion, -14.9^Δ; nondeletion, -12.3^Δ) and no reoperations.

The 15q11.2-q13 deletions confer a distinct oculoalbinism phenotype mediated by OCA2 haploinsufficiency, featuring high myopia, severe astigmatism, and iris hypopigmentation. Standardized strabismus surgery achieves stable alignment across genotypes, supporting genotype-guided refractive surveillance and validating exotropia correction as an effective AS intervention.