Axenfeld syndrome is a rare autosomal dominant disorder that affects the development of the skeleton, teeth, eyes and abdominal region. The syndrome is named after the two ophthalmologists Theodor Axenfeld (Germany) and Herwig Rieger (Austria), who described the syndrome in 1920 and 1935 respectively. The best known but not the only symptom of this syndrome is glaucoma. Genetic testing is important for the diagnosis and for prenatal diagnosis as the condition is hereditary.
- Synonyms Axenfeld-Rieger syndrome
- Epidemiology skeletal disorder
- Causes and heredity of the disease
- Symptoms of eyes (glaucoma) and face
- Diagnosis and examinations
- Treatment of the condition
- Prognosis
Synonyms Axenfeld-Rieger syndrome
Patients sometimes use various names for Axenfeld-Rieger syndrome:
- ARS
- Axenfeld and Rieger anomaly
- Axenfeld anomaly
- Axenfeld syndrome
- AXRA
- AXRS
- Goniodysgenesis-hypodontia
- Iridogoniodysgenesis with physical anomalies
- RGS
- Rieger anomaly
- Rieger syndrome
Epidemiology skeletal disorder
Axenfeld-Rieger syndrome has an estimated prevalence of 1 in 200,000 people. There are equal numbers of men and women. Most cases are diagnosed in childhood. However, glaucoma, one of the main symptoms, usually occurs in late childhood or in adults.
Causes and heredity of the disease
Errors in fetal development during the first three months of pregnancy – especially of the eyes and teeth – lead to the syndrome. Axenfeld-Rieger syndrome is a consequence of mutations (alterations) in at least two known genes: PITX2 and FOXC1. Researchers have described three types of the skeletal disorder numbered 1 to 3. The difference lies in the genetic cause. PITX2 gene mutations cause type 1 and FOXC1 gene mutations lead to type 3. The gene associated with type 2 is likely located on chromosome 13, but it has not yet been identified. The syndrome is inherited in an autosomal dominant manner.
A new mutation may also lead to the Axenfeld-Rieger syndrome. This means that the genetic mutation in patients occurs spontaneously and is not inherited from either parent. Parents of a child with a new mutation generally do not have an increased risk of having a child with the condition. However, the new genetic mutation is hereditary and there is a risk that the child will later pass on the mutated gene to his/her children.
Symptoms of eyes (glaucoma) and face
Eyes
Eye abnormalities are the best-known symptoms of this syndrome. The malformations and abnormalities are mainly localized to the anterior segment of the eye and involve the cornea and the iris. Occasionally patients have megalocornea or microcornea. An ophthalmologist also notices in patients an opaque ring around the outer edge of the cornea as well as adhesions in the front of the eye. In addition, in patients the pupil is not always in the center of the iris, which leads to photophobia (medical term for “photo aversion”) and excessive tearing. About half of affected patients develop glaucoma, a serious eye condition in which eye pressure increases. The ophthalmologist measures this using tonometry. Glaucoma usually occurs in late childhood or in adults in patients with Axenfeld-Rieger syndrome. Nevertheless, glaucoma is possible from childhood. Glaucoma makes a patient visually impaired or even completely blind.
Face
The symptoms of Axenfeld-Rieger syndrome may affect other parts of the body. Many affected patients have various facial abnormalities such as widely spaced eyes (hypertelorism), underdeveloped ears, an underdeveloped upper jaw with protruding lower lip, a flat face with a wide, flat nasal bridge and a prominent forehead. The condition is also associated with dental abnormalities such as abnormally small teeth (microdontia), few teeth (oligodontia) or cone-shaped teeth.
Other symptoms
Some patients with Axenfeld-Rieger syndrome have extra folds of skin around their belly button or an umbilical hernia (bulge of abdominal wall around belly button). Sometimes men also suffer from hypospadias. This is a congenital defect in which the urethra does not open at the tip of the penis but at the bottom of the glans or even halfway or at the base of the penis. Other less common symptoms include heart defects, sensorineural hearing loss, narrowing of the anus (anal stenosis), and abnormalities of the pituitary gland resulting in retarded growth.
Diagnosis and examinations
Physical examination
The diagnosis is generally made via the typical eye abnormalities. In some cases, diagnosis does not occur until early childhood when the small cone-shaped teeth are visible. The diagnosis is confirmed through genetic testing. This is also useful for prenatal diagnosis.
Differential diagnosis
The differential diagnoses of the skeletal disorder include iris hypoplasia, primary congenital glaucoma, and Peter’s anomaly.
Dentures are sometimes necessary / Source: Jim Sneddon, Flickr (CC BY-2.0)
Treatment of the condition
The treatment of Rieger syndrome is symptomatic and supportive. The patient should visit the ophthalmologist regularly for check-ups to detect and treat eye problems as best as possible. Initially, the ophthalmologist treats glaucoma with eye drops for which the patient uses correct eye drop guidelines, but sometimes surgery is required. The development of teeth and jaws is regularly monitored by an orthodontist and/or a pediatric dentist. Dentures (prosthesis) are sometimes necessary for dental abnormalities. Furthermore, genetic research is useful for the patient and his family.
Prognosis
No information is known regarding the prognosis of patients suffering from Axenfeld-Rieger syndrome.
