Renal coloboma syndrome: Year of the Zebra 2025

Renal coloboma syndrome, also known as papillorenal syndrome, is a genetic condition that affects the development of the kidneys and eyes. Most cases are caused by changes in the PAX2 gene, which codes for a protein that acts as a transcription factor.

Transcription factors like PAX2 help regulate the activity of other genes by acting as "switches" that turn genes on or off, called gene expression, as needed. The timing and coordination of gene expression is crucial in the early weeks of fetal development, when all the organs begin to develop. Specifically, PAX2 orchestrates the development of the kidneys, urogenital system, eyes, and parts of the ear, turning them into functional structures.

Typically, inheritance of renal coloboma syndrome follows an autosomal dominant pattern, meaning only one copy of the mutated gene is needed to cause the condition. However, in about half of cases, there doesn’t seem to be any mutation in the PAX2 gene; meaning there are likely other mechanisms involved.

Clinically, individuals with renal coloboma syndrome tend to have small, underdeveloped kidneys that don’t function fully, often resulting in kidney failure by early adulthood.

The most common eye manifestation is a coloboma of the optic disc, a birth defect where the optic disc, or the point where the optic nerve exits the eye, appears larger and hollowed because it didn’t develop as usual. Depending on the extent of the coloboma, individuals may experience vision loss or blind spots. This is especially true when coloboma affects the macula, which is the part of the eye responsible for the sharp, central vision needed for activities like reading or driving.