The Developmental Landscape of Children With Uveal Coloboma and Its Relationship With Clinical Phenotype and Genetics

Uveal coloboma may be an isolated finding or present as part of a syndrome, informed by systemic testing. Genetic testing may elucidate an underlying cause of disease. The likelihood of developmental delay in children with coloboma has not been well-studied. We examined the rates of developmental delay in coloboma patients with syndromic vs nonsyndromic presentations and with positive and negative molecular diagnoses.

Seventy patients with coloboma underwent a battery of systemic testing, molecular diagnosis, and cognitive and/or adaptive behavioral testing between 2009 and 2023. Patients with ≥2 abnormal systemic findings, excluding ocular or developmental delay, were classified as syndromic. The associations between delay and syndromic diagnosis or positive molecular testing were analyzed with logistic regression.

The mean age of participants was 3.97 years. Twenty-three patients were syndromic. Causative variants were identified in 13 cases. Individuals with a syndromic presentation had greater odds of having or reporting developmental delay than those with a nonsyndromic presentation (odds ratio [95% confidence interval] = 4.81 [1.67, 14.69], Z = 2.85, P = .004). A syndromic diagnosis also increased the likelihood of having a solved genetic diagnosis (odds ratio [95% confidence interval] = 6.91 [1.94, 28.89], Z = 2.86, P = .004).

Systemic findings are common in patients presenting with isolated coloboma, underscoring the need for deep phenotyping. In our study, a molecular diagnosis was obtained in only a minority, implying undiscovered genetic or environmental factors. Those patients with ≥2 systemic findings were more likely to be developmentally delayed and to have a positive molecular diagnosis. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.