Orkun Kaymaz

Introduction

Axenfeld-Rieger Syndrome is a rare congenital disorder characterized by a wide spectrum of ocular and extraocular anomalies. This condition primarily affects the anterior segment of the eye and various facial structures, leading to a range of clinical manifestations that require a multidisciplinary approach for effective management. In this review, we will delve into the aetiology and pathophysiology of Axenfeld-Rieger Syndrome, explore its clinical manifestations, and management.

Aetiology and Pathophysiology

Axenfeld-Rieger Syndrome is primarily of genetic origin and is associated with mutations in several key genes. The two most frequently implicated genes are FOXC1 and PITX2 (1). These mutations disrupt normal neural crest cell differentiation and migration during embryonic development (1, 2). Neural crest cells play a crucial role in forming tissues in the anterior segment of the eye, as well as craniofacial structures (1).

Clinical Manifestations

The clinical manifestations of Axenfeld-Rieger Syndrome can be profound and diverse, primarily affecting the eye but also involving various systemic structures. Ocular features include iris stromal hypoplasia, corectopia, polycoria, and posterior embryotoxon (2, 3). These ocular abnormalities often lead to glaucoma, which can be severe and sight-threatening if left untreated.

Extraocular features include craniofacial anomalies, including maxillary hypoplasia and hypertelorism, as well as dental abnormalities such as microdontia and hypodontia. In some cases, systemic issues can be present, affecting the cardiovascular system (congenital heart defects), renal system (renal anomalies), and the umbilicus (omphalocele) (1).

Given the wide range of clinical features, early and comprehensive evaluation by a team of specialists is crucial for timely diagnosis and to address potential systemic complications.

Management

The management of Axenfeld-Rieger Syndrome is tailored to address the specific clinical features and associated complications in each patient. Ophthalmological management is focused on monitoring and treating glaucoma, a common and potentially vision-threatening complication. Surgical interventions, including trabeculectomy, may be necessary to control intraocular pressure and preserve vision (1, 2).

Craniofacial and dental anomalies often require the expertise of oral and maxillofacial surgeons, orthodontists, and prosthodontists to address structural and aesthetic concerns. Systemic involvement necessitates a multidisciplinary approach, including cardiology, nephrology, and general pediatric care to manage cardiovascular, renal, and umbilical abnormalities, respectively (1, 2).

Genetic counseling is imperative for affected families, as Axenfeld-Rieger Syndrome has a hereditary component, and understanding the genetic basis of the condition is crucial for informed reproductive decisions (1, 3).

Conclusion

Axenfeld-Rieger Syndrome is a rare and complex genetic disorder with a wide range of clinical manifestations, particularly affecting the eye and craniofacial structures. Its management requires a multidisciplinary approach to address ocular, craniofacial, dental, and systemic complications. As research continues to unravel the genetic intricacies of the syndrome, we anticipate that it will pave the way for innovative therapeutic strategies and improve the long-term outcomes for individuals living with Axenfeld-Rieger Syndrome.

References

1. Zamora EA, Salini B. Axenfeld-Rieger Syndrome. [Updated Oct 24 2022]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538504/
2. Axenfeld Rieger Syndrome [Internet]. [cited Nov 4 2023]. Available from: https://eyewiki.aao.org/Axenfeld_Rieger_Syndrome#:~:text=Axenfled%2DRieger%20syndrome%20is%20an,crest%20cell%20differentiation%20and%20migration.
3. Chang TC, Summers CG, Schimmenti LA, et al. Axenfeld-Rieger syndrome: new perspectives British Journal of Ophthalmology 2012;96:318-322.