Axenfeld-Rieger Syndrome: A Case Series

Abstract

Axenfeld-Rieger syndrome (ARS) is a genetic disorder characterized by two key components: anterior segment dysgenesis and systemic abnormalities.
Regarding ocular features, posterior embryotoxon (anterior displacement of Schwalbe’s line) is a hallmark. Rieger anomaly comprehends congenital iris abnormalities. When accompanied by systemic findings such as facial bone defects, odontological, pituitary or umbilical abnormalities, the condition is referred to as Rieger syndrome. Axenfeld anomaly and Rieger syndrome present simultaneously make the diagnosis of ARS. In rare cases, hearing loss and cardiac defects may also appear.
Patients with ARS have an increased risk of developing glaucoma due to impaired drainage of aqueous humor. ARS is typically inherited as autosomal dominant but can also occur sporadically. Mutations in PITX2, FOXC1, PAX6, FOXO1A, and CYP1B1 genes underlie ARS’s genetic diversity. The objective is to present clinical manifestations, treatment approaches, and outcomes of ARS, contributing to its understanding and management. We present a case series of patients with ARS from the ophthalmology department of Hospital de São João, Porto, Portugal. Five patients with ARS with different variants involving PITX2 and FOXC1 genes, in heterozygosity, are presented: a two-year-old girl with a deletion of PITX2 gene; a seven-year-old girl and her forty-six-year-old mother with a duplication of exon 1 of FOXC1 gene; a eleven-year-old boy with deletion and substitution of FOXC1 gene; and a fifty-seven-year-old male with a deletion of the exon 1 of FOXC1 gene.
Posterior embryotoxon, corectopia and iris hypoplasia are prevalent among the majority of patients. One patient exhibits mild ocular abnormalities. Notably, three patients have developed glaucoma, with two requiring ocular surgery. The eldest patient, most probably attributable to a delayed diagnosis, is the only individual with a substantial degree of visual impairment. Systemic involvement is variable among patients and includes mostly hypertelorism, sensorineural hearing loss and cardiac abnormalities.
To conclude, our series highlights the diverse clinical presentations and 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 meticulous glaucoma management.