Axenfeld-Rieger syndrome

This is part of Rare diseases.

Diagnosis: Axenfeld-Rieger syndrome

Synonyms: Axenfeld anomaly, Rieger anomaly

Date of publication: 2011-03-16
Version: 1.0

ICD 10 code


The disease

Axenfeld-Rieger syndrome (ARS) is characterised by congenital abnormalities of the teeth and anterior segment of the eye, and also affects various organs. The combination and extent of symptoms vary greatly between individuals. Many people with the syndrome develop glaucoma, the most serious eye complication.

Previously, abnormalities were grouped under Axenfeld anomaly or Rieger anomaly. However, the term Axenfeld-Rieger syndrome is now thought to be more correct as it better describes the combination of symptoms associated with the syndrome. Genetic research has shown that the two sub-groups are related.

The syndrome was named after the two opthamologists Theodor Axenfeld (Germany) och Herwig Rieger (Austria), who described it in 1920 and 1935 respectively.

Rieger anomaly makes up one element of SHORT syndrome. SHORT is an acronym indicating the symptoms characteristic of the syndrome: S is for short stature, H for hyperextensibility of joints and inguinal hernia, O för ocular depression, R for Rieger anomaly and T for teething delay.


There are no definite figures showing the incidence of Axenfeld-Rieger syndrome in Sweden, but it is estimated that it affects five individuals in every one million inhabitants.


The syndrome is caused by developmental defects, mainly of the eyes and teeth, during the first three months of pregnancy. Mutations in certain genes have been established. Approximately 40 per cent of individuals with the syndrome have some form of genetic mutation, while no genetic abnormalities have been identified in the remaining individuals.

Axenfeld-Rieger syndrome can be divided into three types. Type 1 is caused by a mutation in gene PITX2 on chromosome 4. It is believed that type 2 is caused by a mutation on chromosome 13, possibly in gene FOXAO1. Type 3 is caused by a mutation in gene FOXC1 on chromosome 6.

One theory is that Rieger anomaly and SHORT syndrome are different expressions of the same mutation on gene PITX2.


The inheritance pattern of Axenfeld-Rieger syndrome is autosomal dominant. This means that one of the parents has the disease, and so has one normal gene and one mutated gene. Sons and daughters of this parent have a 50 per cent risk of inheriting the disease. Children who do not inherit the mutated gene do not have the disorder and do not pass it down.

Figure: Autosomal dominant inheritance

Axenfeld-Rieger syndrome can also be caused by a new mutation. This means that the genetic mutation occurs in an individual for the first time and is not inherited from either parent. Consequently, parents with a child with a new mutation generally do not have an increased risk of having another child with the disorder. However, the new genetic mutation will be hereditary and an adult with this mutation risks passing on the mutated gene to his/her children.


Although the genetic mutation may be the same within a family, the combination and severity of symptoms can vary greatly between individual members.

Both eyes are affected, with abnormalities in the corneal periphery, in the anterior chamber angle including the trabecular meshwork (a sophisticated filtering device) and the iris. See figure below.

Figure: Cross-section of eye

Figure: Cross-section of eye

The iris may be so atrophied or thin that holes develop in it, causing the pupil to alter its shape and position.

Slightly more than half of those with the syndrome develop glaucoma. This condition means that pressure within the eye is elevated, which can damage the optic nerve. If detected early, glaucoma is treatable. However, if left untreated it may lead to severely impaired vision or even blindness. The most common symptoms of glaucoma are: photophobia (an excessive sensitivity to light), increased tear flow, clouding of the cornea, buphtalmus (enlarged eye) and impaired vision. Glaucoma is usually detected during late childhood, in puberty or early adulthood. It is the most severe eye complication associated with Axenfeld-Rieger syndrome.

Others symptoms commonly include abnormalities of teeth and the facial skeleton. The extent of the abnormalities varies greatly. Teeth, for example, may be small, have distinctive crown and root formations (conical teeth) and abnormal surfaces. One or more teeth may be absent. The premolars and front teeth are often missing. When teeth are absent, parts of the jaw may not develop normally. Abnormalities in the skeleton of the face mean that the development of the upper jaw and the mid-facial area is impaired. This may cause an underbite (when the lower front teeth project beyond the upper front teeth), crossbite or open bite. The distance between the eyes may be increased (hypertelorism) and the nose may be flat.

The development of the umbilical cord may sometimes be affected, presenting as excess skin around the navel. In some boys the urethra opens on the underside of the penis (hypospadia). The heart and the pituitary gland may also be affected. Various cardiac abnormalities have been documented, including an opening in the wall between the atria of the heart (atrial septal defect). If the pituitary gland is affected, it can result in impaired levels of growth hormone, resulting in restricted growth.

Some people with the syndrome may have a degree of mental disability.


A diagnosis is indicated by a combination of specific symptoms. As the risk of glaucoma is high, it is important that the diagnosis is made as early as possible. For this reason the child should be seen by an ophthalmologist. If the syndrome is suspected, contact should also be made with a dentist.

If the child’s permanent teeth erupt late a paediatric dentist or specialist in orthodontic braces may be consulted.

Children with the syndrome should also be examined by a paediatrician to determine whether there are other abnormalities.

As the inheritance pattern is autosomal dominant, if either parent is known to have the syndrome the baby should be examined for early signs.

It is usually possible to make a diagnosis based on DNA testing. Pre-natal diagnosis is possible in families where the mutation is known.


Both children and adults with Axenfeld-Rieger syndrome require regular monitoring by an ophthalmologist. As glaucoma can present at any age, pressure in the eye should be checked on a regular basis. Glaucoma usually requires surgical intervention although treatment also includes eye drops. Eye examinations, including eye pressure testing in small children, is often carried out under anaesthesia.

The child’s vision must also be checked at regular intervals. Spectacles may be required. If vision differs between the eyes, the child’s best eye should be covered at certain times of the day in order to stimulate vision in the other eye. This treatment is usually supervised by specially trained eye care professionals (orthoptists).

If glaucoma is found in both eyes there is an increased risk that sight will be affected. Children with impaired vision require early contact with a habilitation team at a low vision centre. If children have a mental disability, a habilitation programme which optimises their potential is necessary.

A habilitation team includes professionals with special expertise in how disability affects everyday life, health and development. Support and treatment take place within the medical, educational, psychological, social and technical fields. The measures focus on existing needs, may vary over time and are planned in collaboration with individuals close to the child. They also include information about support offered by the local authority.

Children with visual impairments attend local authorities’ ordinary daycare centers and schools. To ensure that children are taught according to the correct methods and with appropriate aids, school staff require the help and guidance of a teacher with training in visual disabilities. At the Resource Centre for the Visually Impaired, operating under the aegis of The National Agency for Special Needs Education and Schools in Stockholm and Örebro, there are professionals who can give advice on visual disability. (See under “National and Regional Resources in Sweden.”)

The development of teeth and jaws should be monitored regularly by a specialist in orthodontics and/or a paediatric dentist. While the child is growing up, appearance and functionality may be improved by temporary replacements for missing teeth. When the individual has stopped growing, dental implants may be fitted, preferably by a team including a dentist specialising in replacing missing teeth (prosthethic specialist), an oral and maxillofacial surgeon and a specialist in dental orthotics (braces).

Individuals growing up with visual impairments, or developing them later in life, require contact with a low vision centre or similar. If they also have mental disabilities, people with the syndrome also require individual habilitation programmes in adulthood.

Social life and choice of occupation may be affected by visual impairment. However, much can be done to provide support and compensate as far as possible for visual disabilities. When necessary, the Swedish Public Employment Services can provide support and information on choice of occupation and the Swedish Regional Social Insurance Offices can assist in adapting the work environment.

Practical advice


National and regional resources in Sweden

Diagnostic resources are available at many of Sweden’s eye clinics. Special expertise on congenital glaucoma is available at The Eye Clinic, Uppsala University Hospital, SE-751 85 Uppsala, Sweden. Tel: +46 18 611 00 00.

The Swedish National Agency for Special Needs Education and Schools is a national organisation covering the whole country. The organisation’s role is to give special educational support to local and other authorities with responsibility for daycare, pre-schools, schools, independent educational establishments and adult education. National resource centres with specialist expertise carry out investigations, organise visits for children and young people and provide information and training for parents, teachers and other personnel. Swedish Resource Centres for the Visually Impaired are located in Stockholm and Örebro.

The Resource Centre for the Visually Impaired - Örebro, Eriksbergsgatan 3, Box 9024, SE-702 30 Örebro, Sweden. Tel: +46 10 473 50 00, email: rc.syn.orebro@spsm.se, www.spsm.se.

The Resource Centre for the Visually Impaired - Örebro, has an associated special school for visually impaired children and children with additional disabilities.

The Resource Centre for the Visually Impaired - Stockholm, Rålambsvägen 32 B, Box 12161, SE-102 26 Stockholm, Sweden. Tel: +46 8 737 16 00, fax +46 8 737 16 99, email: rc.syn.stockholm@spsm.se, www.spsm.se.

Resource personnel


Professor Gerd Holmström, The Eye Clinic, Uppsala University Hospital, SE-751 85 Uppsala, Sweden. Tel: +46 18 611 00 00.

Orthodontic dentist

Senior orthodontic dentist Anna Andlin-Sobocki, Stockholm Cranio-Facial Team, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden. Tel: +46 8 517 700 00.

Courses, exchanges of experience, recreation

SRF, The Swedish Association of the Visually Impaired, organises both local and national courses. For further information see SRF, under “Organizations for the disabled/patient associations etc.”

Organizations for the disabled/patient associations

SRF, The Swedish Association of the Visually Impaired, Sandsborgsvägen 52, SE-122 88 Enskede, Sweden. Tel: +46 8 39 90 00, fax: +46 8 39 93 22, email: info@srf.nu, www.srf.nu.

FUB, The Swedish National Association for Children, Young People and Adults with Intellectual Disabilities. Gävlegatan 18 C, Box 6436, SE-113 82 Stockholm, Sweden. Tel: +46 8 508 866 00, fax: +46 8 508 866 66, email: fub@fub.se, www.fub.se.

Courses, exchanges of experience for personnel

The Resource Centre for the Visually Impaired, part of The Swedish National Agency for Special Needs Education and Schools, provides information and training. Contact The Resource Centres for the Visually Impaired - Orebro or Stockholm - for further information. See addresses under, “National and regional resources in Sweden.”

Research and development (R&D)

Many new genetic mutations have been identified during the last decade. International research is underway into further genetic abnormalities associated with this syndrome.

Information material

An information leaflet on Axenfeld-Rieger syndrome that summarises the information in this database text is available free of charge from the customer service department of the Swedish National Board of Health and Welfare (in Swedish only, article number 2010-4-23.) Address: SE-120 88 Stockholm, Sweden. Tel: +46 75 247 38 80, fax: +46 35 19 75 29, email: publikationsservice@socialstyrelsen.se. Postage will be charged for bulk orders.


Alward WL. Axenfeld-Rieger syndrome in the age of molecular genetics. Am J Ophthalmol 2000; 130: 107-115.

Axenfeld T. Embryotoxon cornea posterius. Berichte der Deutschen ophthalmologischen Gesellschaft 1920; 42: 301.

Caldo-Teixera AS, Puppin-Rontani RM. Management of severe partial hypodontia; case report. J Clin Pediatr Dent 2003; 27: 133-136.

Hjalt TA, Semina EV. Current molecular understanding of Axenfeld-Rieger Syndrome. Expert Rev Mol Med 2005; 25: 1-17.

O’Dwyer EM, Jones DC. Dental anomalies in Axenfeld-Rieger syndrome. Int J Paediatr Dent 2005; 15: 459-463.

Rieger H. Über Subconjunctivitis epibulbous metastatica bei Parotitis epidemica. Archiv für Ophthalmologie, Berlin, 1935, 133: 505-507.

Shields MB, Buckley E, Klintworth GK, Thresher R. Axenfeldt-Rieger syndrome. A spectrum of developmental disorders. Surv Ophthalmol 1985; 29: 387-409.

Tümer Z, Bach-Holm D. Axenfeld-Rieger syndrome and spectrum of PITX2 and FOXC1 mutations. Eur J Hum Genet 2009; 17: 1527-1539.

Database references

OMIM (Online Mendelian Inheritance in Man)
Search: axenfeld-rieger syndrome

Document information

The Swedish Information Centre for Rare Diseases produced and edited this information material.

The medical expert who wrote the draft of this information material is Professor Gerd Holmström, Uppsala University Hospital, Sweden.

Senior orthodontic dentist Anna Andlin-Sobocki, Karolinska University Hospital, Solna, Sweden, has also been involved in producing the material.

An expert group on rare diseases, affiliated with the University of Gothenburg, approved the material prior to publication.

Date of publication: 2011-03-16
Version: 1.0
Publication date of the Swedish version: 2010-06-16

For enquiries contact The Swedish Information Centre for Rare Diseases, The Sahlgrenska Academy at the University of Gothenburg, Box 400, SE-405 30 Gothenburg, Sweden. Tel +46 31 786 55 90, email: ovanligadiagnoser@gu.se.


About the database

This knowledge database provides information on rare diseases and conditions. The information is not intended to be a substitute for professional medical care, nor is it intended to be used as a basis for diagnosis or treatment.