Axenfeld-Rieger syndrome is a rare spectrum of disorders with an autosomal dominant pattern of inheritance ⁶. The syndrome incorporates all of ⁵:

• Axenfeld anomaly: posterior embryotoxon and peripheral irido-corneal adhesions

• Rieger anomaly: findings of Axenfeld anomaly along with corectopia (malposition of pupil), iris thinning and hole in iris

• Rieger syndrome: findings of Rieger anomaly with associated systemic manifestations

Epidemiology

The syndrome is rare with an incidence of 1:200000 live births ². 40-70% of the cases have an associated FOXC1 or PITX2 genetic mutations ³. There is no gender predilection ⁴.

Diagnosis

The syndrome is classified into three types and all types present with ocular abnormalities. Type 1 has mid-facial and dental anomalies with mutation in chromosome 4 and PITX2 gene. Type 2 has auditory and cardiac anomalies with mutation located in chromosome 13. Type 3 involves mutations in chromosome 6 and FOXC1 gene ^2,6.

The diagnosis is mainly clinical and a comprehensive ophthalmological evaluation along with other investigations such as brain CT or MRI, echocardiogram, and hearing evaluation is necessary to detect systemic manifestations ³. 

Clinical presentation

The clinical presentation may include ocular and systemic manifestations ^1-6:

• ocular anomalies, e.g. glaucoma, iris hypoplasia, posterior embryotoxon and corneal opacities

• facial anomalies, e.g. maxillary hypoplasia, mandibular prognathism, hypertelorism, telecanthus, broad nose

• dental anomalies, e.g. oligodontia, delayed tooth eruption, hypoplastic enamels and molars, peg shaped teeth

• neurovascular anomalies

• cardiac defects, e.g. mitral valve regurgitation, hypoplastic left ventricular outflow tract

• redundant periumbilical skin 

• hearing loss

Pathology

Abnormal migration of neural crest cells is responsible for the defects seen in Axenfeld- Rieger syndrome. While there are many potential genetic anomalies which can lead to Axenfeld-Riger syndrome, commonly implicated genetic mutations include:

• PITX2: normally activates DlX2 gene, which is responsible for craniofacial and tooth development ²; PITX2 mutation leads to maxillary and mandibular hypoplasia along with tooth abnormalities ² 

• FOXC1: responsible for the migration and differentiation of mesenchymal cells and mutation in this gene leads to cardiac anomalies and thyroid dysfunction ²

Radiographic features

Given Axenfeld-Rieger syndrome is so heterogenous, the radiographic features ultimately matches the clinical presentation for any given patient. For example, regarding dental anomalies, patients with Axenfeld-Rieger syndrome have unerupted teeth, oligodontia and microdontia visible on orthopantomogram ². 

Various neurological and neurovascular abnormalities have been noted in patients with Axenfeld-Rieger syndrome which can be visualized with brain CT or MRI ¹. White matter abnormalities such as leukoencephalopathy and Dandy-Walker malformation are the most common neurological abnormalities visualized ¹. Others such as ventriculomegaly/hydrocephalus have also been described ¹. Vascular abnormalities may lead to stroke, which includes ischemic and hemorrhagic stroke ¹. 

Treatment and prognosis 

Congenital glaucoma may lead to blindness and requires management using beta-blockers or carbonic anhydrase inhibitors ^3,4. Surgical management is by trabeculectomy, goniotomy or trabeculotomy ^3,4. Hydrocephalus, when present, may require surgical management ¹.

Distraction osteogenesis and orthognathic surgery are needed for maxillary and mandibular hypoplasia ². Dental implants and prosthesis may also be required in the management of oligodontia ². 

History and etymology 

The syndrome is named after Theodor Axenfeld, a German ophthalmologist who described it in 1920 ². Rieger also described it in 1934 ².