Axenfeld–Rieger syndrome

Axenfeld–Rieger syndrome
Axenfeld syndrome.jpg
a) Microdontia and hypodontia. b) Slit pupil and iris atrophy right eye. c) Corectopia with iris atrophy left eye. d) Posterior embryotoxon right eye. e) Posterior embryotoxon left eye. f) Broad peripheral anterior synechiae right eye.
Synonyms	Axenfeld syndrome, Hagedoom syndrome, Rieger anomaly, Axenfeld–Rieger anomaly
Pronunciation
Specialty	Ophthalmology, Medical genetics
Symptoms	Posterior embryotoxon, corectopia, iris hypoplasia, glaucoma, dental abnormalities, facial dysmorphism
Complications	Vision loss due to glaucoma
Usual onset	Congenital (present at birth)
Duration	Lifelong
Types	Axenfeld anomaly, Rieger anomaly, Axenfeld–Rieger syndrome
Causes	Genetic mutation (commonly in PITX2, FOXC1)
Risk factors	Family history of Axenfeld–Rieger syndrome
Diagnosis	Clinical exam, genetic testing, slit lamp examination, gonioscopy
Differential diagnosis	Peter's anomaly, aniridia, Marfan syndrome, Turner syndrome
Prevention	None
Treatment	Intraocular pressure management, glaucoma surgery, dental and craniofacial correction
Medication	Topical beta blockers, carbonic anhydrase inhibitors
Prognosis	Good with proper management; risk of vision loss if untreated
Frequency	Rare (estimated 1 in 200,000)
Deaths	Rare; related to complications from glaucoma if untreated

Axenfeld–Rieger syndrome is a rare genetic disorder inherited in an autosomal dominant pattern. It primarily affects the development of the eyes, but can also impact the teeth, facial bones, and other systems.

File:Autosomal dominant - en.svg

Axenfeld–Rieger syndrome has an autosomal dominant pattern of inheritance.

Pathophysiology

The disorder involves mutations in several transcription factor genes that play key roles in embryonic development. These genes include PITX2, FOXC1, and potentially FOXO1A. These mutations disrupt the normal development of the anterior segment of the eye, leading to characteristic abnormalities such as posterior embryotoxon, corectopia, iris hypoplasia, and increased risk for glaucoma.

Axenfeld–Rieger syndrome is inherited in an autosomal dominant manner, meaning only one copy of the altered gene from an affected parent is sufficient to cause the disorder. Each child of an affected parent has a 50% chance of inheriting the condition.

Diagnosis

While often recognized due to its ocular features, Axenfeld–Rieger syndrome may also present with dental, craniofacial, and skeletal anomalies. The most characteristic ocular sign is a prominent and displaced Schwalbe's line, called a posterior embryotoxon. In more severe cases, the iris may adhere to the cornea, and patients often present with elevated intraocular pressure or glaucoma.

Genetic testing can confirm mutations in known associated genes. Approximately 40% of individuals diagnosed with Axenfeld–Rieger syndrome have identifiable mutations in PITX2, FOXC1, or PAX6.

Classification

Axenfeld–Rieger syndrome is classified into three main subtypes based on the associated gene:

Type	OMIM	Gene
Type 1	Online Mendelian Inheritance in Man (OMIM) 180500	PITX2
Type 2	Online Mendelian Inheritance in Man (OMIM) 601499	Possibly FOXO1A
Type 3	Online Mendelian Inheritance in Man (OMIM) 602482	FOXC1
De Hauwere syndrome (variant)	Online Mendelian Inheritance in Man (OMIM) 109120	Unknown

Clinical Features

In addition to ocular abnormalities, individuals may present with:

• Hypodontia, microdontia, or other dental anomalies
• Maxillary hypoplasia and midface retrusion
• Umbilical abnormalities
• Short stature
• Hearing loss
• Developmental delays in some cases

Glaucoma is a major complication, occurring in 50% of patients, and often presents in childhood or adolescence.

Management

There is currently no cure for Axenfeld–Rieger syndrome. Management focuses on monitoring and treating individual complications:

• Ophthalmologic care – Regular screening for glaucoma and intraocular pressure management through medications or surgical interventions
• Dental care – Management of missing or malformed teeth
• Genetic counseling – Important for affected families, especially in cases considering prenatal diagnosis or preimplantation genetic diagnosis

Eponym

The syndrome is named after German ophthalmologist Theodor Axenfeld and Austrian ophthalmologist Hans Rieger, who documented the ocular and systemic features, respectively.

Related Conditions

• Primary juvenile glaucoma
• Anterior segment dysgenesis
• Rieger anomaly
• Peters anomaly
• SHORT syndrome

See also

• Glaucoma
• Schwalbe's line
• Posterior embryotoxon
• Autosomal dominant inheritance
• Chorionic villus sampling
• Amniocentesis
• Preimplantation genetic diagnosis

External Links

• Axenfeld-Rieger syndrome at NIH's Office of Rare Diseases

• Axenfeld-Rieger anomaly with cardiac defects and sensorineural hearing loss at NIH's Office of Rare Diseases

• OMIM – Online Mendelian Inheritance in Man