Clinical and genetic spectrum of coloboma: A proposal for a comprehensive approach to pediatric patients

Purpose

to analyze pediatric coloboma cases to (1) identify ophthalmological and systemic associations, (2) establish the variables with the highest probability of reaching a genetic diagnosis and worse visual prognosis and (3) propose a clinical and genetical assessment protocol.

Design and methods

Descriptive, retrospective and single-center study. Patients under 18 years of age diagnosed with iris, chorio-retinal and/or optic disc coloboma under follow-up by a reference Pediatric Ophthalmology Unit have been selected from January 2012 to December 2022. A comprehensive data collection and analysis was performed to evaluate phenotype, molecular and prognosis correlations.

Results

A total of 214 patients with a mean age of 11.3 years (6.8 SD) were included (57% female). Among them, 50.9% presented with bilateral coloboma and 66.8% with other ophthalmological alterations (28.5% with microphthalmia). Systemic involvement was observed in 28%, being neurological dysfunction (24.8%) and craniofacial dysmorphic features (18.2%) the most frequent. Molecular diagnosis was reached in 19.2% and clinical exome sequencing had the highest diagnostic yield (22.2%). Bilaterality, macula involvement, short stature and neurological, craniofacial dysmorphic, cardiovascular, and renal anomalies were associated with reaching a genetic diagnosis (p < 0.05). Patients with craniofacial dysmorphic features, hearing, neurologic, cardiac abnormalities or short stature had a worse visual prognosis according with a multivariate model (p < 0.05). A diagnosis and follow-up protocol was developed.

Conclusion

It is imperative to ascertain diagnostic and prognostic indicators in individuals with coloboma to facilitate genetic counseling, mitigate potential complications, and enhance the overall well-being of patients and their families