Axenfeld-Rieger syndrome

Synonyms

4

Overview

Axenfeld-Rieger syndrome is primarily an eye disorder that affects the development of the eye and it can also affect other parts of the body. This condition is characterized by abnormalities of the front part of the eye, an area known as the anterior segment. For example, the colored part of the eye (the iris), may be thin or poorly developed. The iris normally has a single central hole, called the pupil, through which light enters the eye. People with Axenfeld-Rieger syndrome often have a pupil that is off-center (corectopia) or extra holes in the iris that can look like multiple pupils (polycoria). This condition can also cause abnormalities of the cornea, which is the clear front covering of the eye.
About half of affected individuals develop glaucoma, a serious condition that increases pressure inside the eye. When glaucoma occurs with Axenfeld-Rieger syndrome, it most often develops in late childhood or adolescence, although it can occur as early as infancy. Glaucoma can cause vision loss or blindness.

The signs and symptoms of Axenfeld-Rieger syndrome can also affect other parts of the body. Many affected individuals have distinctive facial features such as widely spaced eyes (hypertelorism); a flattened mid-face with a broad, flat nasal bridge; and a prominent forehead. The condition is also associated with dental abnormalities including unusually small teeth (microdontia) or fewer than normal teeth (oligodontia). Some people with Axenfeld-Rieger syndrome have extra folds of skin around their belly button (redundant periumbilical skin). Other, less common features can include heart defects, the opening of the urethra on the underside of the penis (hypospadias), narrowing of the anus (anal stenosis), and abnormalities of the pituitary gland that can result in slow growth.

Researchers have described at least three types of Axenfeld-Rieger syndrome. The types, which are numbered 1 through 3, are distinguished by their genetic cause. Axenfeld-Rieger syndrome type 1 is caused by spelling mistakes (mutations) in the PITX2 gene. Axenfeld-Rieger syndrome type 3is caused by mutations in the FOXC1 gene. The gene that causes Axenfeld-Rieger syndrome type 2 is not known, but it is located on chromosome 13. Axenfeld-Rieger syndrome has an autosomal dominant pattern of inheritance.

 

Symptoms

Axenfeld-Rieger syndrome is an eye disorder. People with this disorder typically have cornea defects, which is the clear cover on the front of the eye. They may have a cloudy cornea or posterior embryotoxin, which is when you can see an opague ring around the outer edge of the cornea. People with this disorder can also have issues with their iris, which is the colored part of the eye. They typically have iris stands, which is connective tissue that connects the iris with the lens. There may be issues with the pupils as well, which is the black opening in the eye. One of the pupils may be in the wrong location (corectopia), the pupils may be abnormally large or small, or there may be extra pupils (polycoria). Click here to view a diagram of the eye.

About 50% of people with this syndrome develop glaucoma, which is a serious condition that increases pressure inside of the eye. This may cause vision loss or blindness. People with this syndrome can also have strabismus (cross-eye), cataracts (cloudy lens), macular degeneration (eye disorder that causes vision loss), or coloboma (a hole in a structure in the eye).

Even though Axenfeld-Rieger syndrome is primarily an eye disorder, people with this syndrome can have symptoms that affect other parts of the body too. These symptoms mostly involve the teeth and facial bones. Symptoms affecting the teeth include cone-shaped teeth (peg-like incisors), missing teeth (oligodontia), small teeth (microdontia), and abnormal spacing of the teeth. Symptoms affecting the facial bones include things such as an underdeveloped jaw, a protruding lower lip, and widely-spaced eyes. Other symptoms include extra folds of skin around the belly button, heart defects, or other more rare birth defects.

Causes

Axenfeld-Rieger syndrome is inherited in an autosomal dominant manner. In autosomal dominant conditions, if there is a spelling mistake (a mutation) in just one copy of that gene, then that person will develop the condition. This mutation can be inherited from a parent, or it can happen by chance for the first time in that one person, which is called a de novo mutation.

Each child of an individual with Axenfeld-Rieger syndrome has a 50% chance of inheriting the mutation. Children who inherit the mutation will have Axenfeld-Rieger syndrome. Although, their symptoms could be more or less severe than their parent's.

Diagnosis

The disorder is commonly recognized by the presence of characteristic eye defects. In some cases these are delayed and diagnosis may be deferred until early childhood when the small, conical teeth become apparent.

Although most recognized for its correlation with the onset of glaucoma, the malformation is not limited to the eye, as Axenfeld syndrome when associated with the PITX2 genetic mutation usually presents congenital malformations of the face, teeth, and skeletal system.

The most characteristic feature affecting the eye is a distinct corneal posterior arcuate ring, known as an "embryotoxon". The iris is commonly adherent to the Schwalbe's line (posterior surface of the cornea).

Analysis of genetic samples from affected patients could result in the discovery of one of the three known genetic mutations which cause the syndrome. About 40% of Axenfeld-Rieger sufferers display mutations in one of the genes known as PAX6,[8][9] PITX2 and FOXC1.

Detection of any of these mutations can give patients a clear diagnosis and post and antenatal procedures such as Preimplantation genetic diagnosis, Chorionic villus sampling and Amniocentesis can be offered to patients. From here, it is a decision for the prospective parent to decide whether they wish to use the genetic diagnosis that they have acquired to prevent the condition from being passed on to future generations.

Treatment

The treatment of Rieger syndrome is symptomatic and supportive and prostheses are used for dental malformations. Also, Genetic counseling may be of benefit for patients and their families.

Resources

• NIH
• Genetics Home Reference