Axenfeld-Rieger Syndrome: A Case Series

Axenfeld-Rieger syndrome (ARS) is a genetic disorder, characterized by 2 key components: anterior segment dysgenesis and systemic abnormalities.

Regarding ocular features, posterior embryotoxon is a hallmark, which involves anterior displacement of Schwalbe's line. Additionally, Rieger anomaly comprehends congenital iris abnormalities, including iris hypoplasia, corectopia and polycoria. When these iris anomalies are accompanied by systemic findings such as odontological problems, facial bone defects (including maxillary hypoplasia), umbilical abnormalities or pituitary involvement, the condition is referred to as Rieger syndrome.

When both Axenfeld anomaly and Rieger syndrome are present simultaneously in an individual, the diagnosis is ARS.

In rare cases, hearing loss and cardiac defects also appear. ARS is typically inherited as autosomal dominant but can also occur sporadically. It has complete penetrance with variable expressivity and 50% glaucoma risk. Mutations in PITX2, FOXC1, PAX6, FOXO1A and CYP1B1 genes underlie ARS's genetic diversity, regulating embryonic development gene expression. Due to its complexity ARS requires a comprehensive, multidisciplinary approach for diagnosis, management and genetic basis understanding.

We present a case series of patients with diagnosed ARS from the ophthalmology consultation of Hospital de São João, Porto, Portugal.

A total of 5 patients with ARS with different variants involving PITX2 and FOXC1 genes, in heterozygosity: a 2 years-old girl with a delection of the PITX2 gene; a 7 years-old girl and her 46 years-old mother, a 11 years-old boy and a 57 years old male with FOXC1 mutations.

Exuberant and extensive posterior embryotoxon, corectopia and iris hypoplasia are prevalent among the majority of patients. Only two patients exhibit mild ocular abnormalities. Notably, 3 patients have developed glaucoma, with 2 requiring ocular surgery (trabeculotomy). The eldest patient, most probably attributable to a delayed diagnosis and the accumulated burden of enduring the disease for several years, is the only individual with a substantial degree of hypovision.

To conclude, our case series on Axenfeld-Rieger syndrome offers valuable insights into the diverse clinical presentations and the challenges faced by affected individuals. As glaucoma management plays a pivotal role in mitigating potential vision loss in these cases, our findings underscore the paramount importance of early diagnosis and the meticulous management of glaucoma. By fostering a deeper understanding of the syndrome's variability and outcomes, we can collectively emphasize the critical need for effective glaucoma management, thereby improving the overall quality of life for individuals with this rare disorder.