Axenfeld-Rieger Syndrome: An Insight

Introduction

Axenfeld-Rieger syndrome or ARS is a congenital or developmental syndrome affecting multiple body systems; majorly, the development of the eye gets compromised. Though the defects in the eye prevail, other body organs are also affected. Approximately fifty percent of the patients suffering from Axenfeld-Rieger syndrome also develop glaucoma (a group of eye conditions that cause vision loss and damage to the optic nerve leading to permanent blindness) in later life.

What Are the Different Types of Axenfeld-Rieger Syndrome?

The prevalence of ARS is scarce. Only one out of two hundred thousand people suffer from the condition. It is multiethnic and affects people of various ethnicities like European, African, Asian, South, and North America. The state does not predispose to a particular age or sex; glaucoma is more common in children and infants.

The Axenfeld-Rieger syndrome can be divided into three types based on the genetic basis.

• Type 1: It caused due to the genetic mutation of PITX2.

• Type 2: The gene linked to Type 2 has not been identified; however, the gene is hypothesized to be located on chromosome 13.

• Type 3: The FOXC1 gene mutation is responsible for type 2 ARS.

What Causes ARS?

The chief cause for the development of the disease is the genetic mutations occurring in the genes involved in the development of the eyes, especially in the structures present in the anterior segment of the eyes. The main genes associated with ARS are:

• PITX2

• FOXC1

People who show mutations in their FOXC1 gene also have abnormalities in other body parts.

Defects in the process of differentiation, migration, and interrupted development of the neural crest cells present in the anterior chamber of the eyes, facial bones, cardiovascular system, and teeth are responsible for the clinical and ocular findings of the disease.ARS can be passed on to future generations. The disease shows an autosomal dominant inheritance pattern; that is, every generation in a family is affected.

What Are the Clinical Presentations of ARS?

Axenfeld-Rieger syndrome is a heterogenous condition (a medical condition with several causes). It presents bilaterally. The development defects associated with the condition affect various body parts, such as the iris, anterior chamber, angle, and trabecular meshwork. Symptoms of ARS are:

Ocular Findings -

• Atrophy (decrease in the number of cells or tissues) of the iris.

• Posterior embryotoxon (greyish-white ridge present on the inner surface of the cornea).

• The iris has generalized atrophy with pupil displacement and anterior chamber dysgenesis similar to the iridocorneal endothelial syndrome (an ophthalmic disorder leading to secondary angle closure glaucoma, corneal edema, and iris atrophy).

• Children present with corneal decompensation, tearing, and poor vision. Adults do not show any pressing symptoms and may require a physical examination of the eyes to detect the problem.

Systemic Findings -

• Redundant umbilical skin.

• Hypodontia (less number of teeth).

• Microdontia (smaller teeth).

• Small maxilla.

• Broad and flat nasal bridge.

• Growth retardation.

• Pituitary gland abnormalities.

• Hypertelorism (large distance between both eyes).

• Cardiovascular abnormalities.

• Short stature.

Patients suffering from ARS develop glaucoma or increased intraocular pressure at an early age (infancy or late childhood and adolescence). Glaucoma of the eye can lead to blindness.

How Are Patients With Rieger Anomaly Syndrome Managed?

The symptoms of ARS are managed both medically and surgically.

• Glaucoma in infants with ARS is treated medically with aqueous suppressants like beta-blockers and carbonic anhydrase inhibitors. However, they cause side effects in children and should be monitored regularly. Prostaglandin analogs are also used to decrease intracranial procedures.

• Tinted contact lenses are recommended for ARS patients with progression of age as these patients also suffer from photophobia (sensitivity to light) as the atrophy of the iris progresses.

• Surgical management is a prerequisite for congenital glaucoma. However, the success rate of surgeries is less and is related to many complications. The various surgeries that can be performed are:

• Goniotomy: It is a procedure performed to reduce lower intraocular pressure and to reduce the use of pressure-lowering medications. It is a relatively safe method for lowering pressure and managing glaucoma.

• Trabeculectomy: This procedure creates an ostium from the anterior chamber through the eye's sclera to provide space for the aqueous flow. It can be performed with or without antifibrotic agents.

• Cyclodestructive Procedures: The ciliary body is destructed to treat the glaucoma of the eyes by destroying the ciliary epithelium, which lowers the pressure.

• Trabeculectomy with Mitomycin C successfully lowers the intra-ocular pressure in almost 80 percent of the cases.

• Glaucoma drainage devices provide a longer success rate, though revision surgeries are required to compensate for the complications linked to the surgery (erosion, dislocation of pupil).

• Refractory glaucomas in children are best treated with drainage devices and cyclo-destructive procedures.

• ARS does not affect the life expectancy and general health of a patient. However, it can have a detrimental effect on vision when associated with glaucoma.

How Are Patients With Axenfeld-Rieger Syndrome Diagnosed?

• The state is easily diagnosed clinically based on the clinical characteristics of the disease. Genetic testing helps in determining the exact cause of the disease. The embryotoxon of the cornea is best visualized using the slit-lamp technique. Regular monitoring of glaucoma is also essential to evaluate the disease progression.

• Gonioscopy helps visualize the extent of the posterior embryotoxon hanging from the anterior chamber. It appears as an arcuate ring that hangs anteriorly to the cornea's and Schwalbe's lines.

What Are the Conditions That Mimic ARS?

The conditions that share similarities with ARS are:

• Iridocorneal endothelial syndrome.

• Peter's anomaly (central corneal opacity with the clear peripheral cornea).

• Iris hypoplasia.

• Congenital ectropion uvea (unilateral anterior chamber dysgenesis).

• Occulodentodigital dysplasia (a congenital disability affecting multiple body parts).

Conclusion

ARS is a rare developmental anomaly of the eye and its structure and is more common in children and infants, leading to congenital glaucoma. Genetic mutations are the main cause of the development of the disease. The entity can be easily diagnosed by physical examination, and glaucoma treatment involves medical and surgical approaches. The disease does not affect the lifespan or health of the patient; however, it compromises the vision.