Axenfeld‐Rieger syndrome combined with a foveal anomaly in a three‐generation family: a case report

Abstract

Background Axenfeld-Rieger syndrome (ARS) is a rare autosomal dominant eye disorder that can also affect other organs of the human body. The condition is primarily characterized by the anterior segmental abnormalities of the eye. Here, we present an observational case series of a three-generation family with ARS and unexpected foveal anomaly. Case presentation A 33-year-old woman was admitted to an Ophthalmology Clinic in Bialystok for left eye congenital cataract surgery. The patient (proband) was diagnosed with visual deterioration, multiple defects of iris, corectopia, displacement of the Schwalbe’s line, and phenotypic characteristics of ARS. A perimetric examination indicated peripheral visual field loss and signs typical for glaucoma. Based on the phenotypic symptoms and genetic test, the patient was diagnosed with Axenfeld Rieger Syndrome. However, the optical coherence tomography of the macula showed foveal anomaly (absence of the physiological pit), which is not typically associated with this genetic disorder. The patient’s family history revealed that her two daughters were undergoing treatment for congenital glaucoma, and one of the daughters also had foveal anomaly the same as her mother. Interestingly, an examination of the patient’s mother showed typical phenotypic features of ARS such as a defect of the iris, posterior embryotoxon, and coloboma, as well as foveal anomaly. A genetic test confirmed PITX2 mutation in both, proband’s two daughters and mother. Conclusions This study highlights the occurrence of ARS with unusual ophthalmic features such as foveal anomaly (absence of the physiological pit) in a three-generation family. Although ARS is known to represent the developmental defects of the anterior segment of the eye, it is very important to perform fundus evaluation to identify associated posterior segment anomalies that may affect visual acuity. The presence of ocular defects not typically associated with ARS suggests a wide spectrum of mutations within PITX2 gene which are required to identify in order to determine genotype- phenotype correlation in ARS affected individuals.

Ophthalmological Manifestations of Axenfeld-Rieger Syndrome: Current Perspectives

“…70 Optic nerve colobomas, hypoplasia, and dysplasia (Figure 2A), foveal hypoplasia (Figure 2B) and atrophy, and chorioretinal colobomas have all been reported in patients with ARS. 16,25,71,72 The importance of recognizing these other abnormalities as part of the disease spectrum is emphasized by phenotypic variations causing delayed diagnosis in individuals belonging to families with genetically confirmed ARS.…”

Axenfeld–Rieger syndrome: orthopedic and orthodontic management in a pediatric patient: a case report

“…Axenfeld-Rieger Syndrome (ARS) is a rare autosomal dominant genetic disease with considerable expressive variability [1], characterized by ocular and non-ocular manifestations (cardiovascular, mild craniofacial abnormalities and dental malformations). In some cases, patients may have short stature, mental retardation and finger malformations [2][3][4][5][6]. An abnormal migration and differentiation of neural crest cells are considered responsible for anomalies in ocular, craniofacial and dental development.…”

In Vivo Assessment of Retinal Phenotypes in Axenfeld–Rieger Syndrome

“…Animal models suggest a role for these genes in posterior segment development with a reduced posterior vitreous chamber noted in pitx2- deficient zebrafish 6 and hyaloid vasculature anomalies seen in both pitx2- and foxc1a- deficient zebrafish. 7 , 8 Posterior segment anomalies have been occasionally reported in humans, including persistent fetal vasculature, 9 macular retinoschisis, 5 and absent foveal pit 10 in one individual each with PITX2- ARS; persistent fetal vasculature 11 and dysplastic optic nerves with peripapillary chorioretinal atrophy 12 in one individual each with FOXC1- ARS; and optic nerve/retinal colobomas in three cases with 6p25 deletions (involving other genes in addition to FOXC1 ) . 1 , 13 , 14 An overlapping phenotype of typical aniridia, caused by variants in PAX6 and characterized by a variable degree of iris hypoplasia, includes malformations in multiple additional ocular tissues, with foveal hypoplasia identified in up to 98.5% of cases and considered to be one of the differentiating features of that phenotype.…”