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Disease Profile

Axenfeld-Rieger syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

Infancy

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ICD-10

Q13.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Rieger syndrome; Iridogoniodysgenesis with somatic anomalies; Goniodysgenesis hypodontia

Categories

Congenital and Genetic Diseases; Digestive Diseases; Endocrine Diseases;

Summary

Axenfeld-Rieger syndrome is a group of disorders that mainly affects the development of the eye. Common eye symptoms include cornea defects and iris defects. People with this syndrome may have an off-center pupil (corectopia) or extra holes in the eyes that can look like multiple pupils (polycoria). About 50% of people with this syndrome develop glaucoma, a condition that increases pressure inside of the eye, and may cause vision loss or blindness. Click here to view a diagram of the eye.[1][2][3][4][5][6] 

Even though Axenfeld-Rieger syndrome is primarily an eye disorder, this syndrome can affect other parts of the body. Most people with this syndrome have distinctive facial features and many have issues with their teeth, including unusually small teeth (microdontia) or fewer than normal teeth (oligodontia). Some people have extra folds of skin around their belly button, heart defects, or other more rare birth defects.[1][2][3][4][5][6]

There are three types of Axenfeld-Rieger syndrome and each has a different genetic cause. Axenfeld-Rieger syndrome type 1 is caused by mutations in the PITX2 geneAxenfeld-Rieger syndrome type 3 is caused by mutations in the FOXC1 gene.[5][7] The gene that causes Axenfeld-Rieger syndrome type 2 is not known, but it is located on chromosome 13.[8] Axenfeld-Rieger syndrome has an autosomal dominant pattern of inheritance. Treatment depend on the symptoms.[5][7][8][6]

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.[1][4][6]

About 50% of people with this syndrome develop glaucoma, which is a 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).[1][4][6]

Even though Axenfeld-Rieger syndrome is primarily an eye disorder, people with this syndrome can also have symptoms that affect other parts of the body. 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 may include 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.[1][2][4][6]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal anterior chamber morphology
0000593
Aplasia/Hypoplasia of the iris
Absent/small iris
Absent/underdeveloped iris

[ more ]

0008053
Posterior embryotoxon
0000627
30%-79% of people have these symptoms
Abnormality of cardiovascular system morphology
0030680
Everted lower lip vermilion
Drooping lower lip
Outward turned lower lip

[ more ]

0000232
Glaucoma
0000501
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Midface retrusion
Decreased size of midface
Midface deficiency
Underdevelopment of midface

[ more ]

0011800
5%-29% of people have these symptoms
Abnormality of the hypothalamus-pituitary axis
0000864
Anal stenosis
Narrowing of anal opening
0002025
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

0005280
Growth delay
Delayed growth
Growth deficiency
Growth failure
Growth retardation
Poor growth
Retarded growth

[ more ]

0001510
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Hypodontia
Failure of development of between one and six teeth
0000668
Hypoplasia of the maxilla
Decreased size of maxilla
Decreased size of upper jaw
Maxillary deficiency
Maxillary retrusion
Small maxilla
Small upper jaw
Small upper jaw bones
Upper jaw deficiency
Upper jaw retrusion

[ more ]

0000327
Hypospadias
0000047
Microdontia
Decreased width of tooth
0000691
Prominent forehead
Pronounced forehead
Protruding forehead

[ more ]

0011220
Redundant skin
Loose redundant skin
Redundant skin folds
Sagging, redundant skin

[ more ]

0001582
Telecanthus
Corners of eye widely separated
0000506
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge

[ more ]

0000431
Percent of people who have these symptoms is not available through HPO
Abnormal heart morphology
Abnormality of the heart
Abnormally shaped heart
Heart defect

[ more ]

0001627
Abnormality of the abdominal wall
0004298
Abnormally prominent line of Schwalbe
0007873
Anal atresia
Absent anus
0002023
Aniridia
Absent iris
0000526
Anterior chamber synechiae
0007833
Atrial septal defect
An opening in the wall separating the top two chambers of the heart
Hole in heart wall separating two upper heart chambers

[ more ]

0001631
Autosomal dominant inheritance
0000006
Blindness
0000618
Cerebellar vermis hypoplasia
0001320
Concave nasal ridge
Boxer's nasal deformity
Boxer's nose deformity
Saddle nose
Ski jump nose

[ more ]

0011120
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Ectopia pupillae
Displaced pupil
0009918
Growth hormone deficiency
0000824
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
Hypoplasia of the iris
Underdeveloped iris
0007676
Inguinal hernia
0000023
Malar flattening
Zygomatic flattening
0000272
Mandibular prognathia
Big lower jaw
Increased projection of lower jaw
Increased size of lower jaw
Large lower jaw
Prominent chin
Prominent lower jaw

[ more ]

0000303
Megalocornea
Enlarged cornea
0000485
Microcornea
Cornea of eye less than 10mm in diameter
0000482
Opacification of the corneal stroma
0007759
Patent ductus arteriosus
0001643
Polycoria
Multiple pupils
0011500
Prominent supraorbital ridges
Prominent brow
0000336
Proptosis
Bulging eye
Eyeballs bulging out
Prominent eyes
Prominent globes
Protruding eyes

[ more ]

0000520
Rieger anomaly
0000558
Sensorineural hearing impairment

Treatment

If glaucoma is present, the goal of treatment is to decrease intra-ocular pressure (IOP). An annual ophthalmologic exam should be done using several specific exams to detect the presence of glaucoma. Should glaucoma develop, eye drops are usually recommended before surgery. Medications that might be prescribed include those that decrease aqueous output (beta-blockers, alpha-agonists and carbonic anhydrase inhibitors). However, alpha-agonists should be used with caution in young children because of possible neurologic effects. Surgery is performed if eye drops are not sufficient in lowering IOP. If surgery is necessary, the procedure of choice is trabeculectomy. Laser surgery may also be indicated. Patients with corectopia (pupil is off center and not located where it should be) and polycoria (more than one pupil is present in the eye) may experience too much sensitivity to light (photophobia), and contact lenses may be helpful.[9][10]

If the person has additional findings, treatment will depend on the symptoms present, and may include surgery to correct facial or dental problems, heart surgery, or corrective surgery for the cases of hypospadia. Short stature due to a growth hormone deficiency may be treated with growth hormone.

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Organizations Providing General Support

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • Genetics Home Reference (GHR) contains information on Axenfeld-Rieger syndrome. This website is maintained by the National Library of Medicine.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        In-Depth Information

        • EyeWiki is an eye encyclopedia written by eye physicians and surgeons that offers an information page on Axenfeld-Rieger syndrome. Please click the link to access this resource.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          The Online Mendelian Inheritance in Man (OMIM)
          The Online Mendelian Inheritance in Man (OMIM)
          Online Mendelian Inheritance in Man (OMIM)
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Axenfeld-Rieger syndrome. Click on the link to view a sample search on this topic.

          References

          1. JD Brandt. Congenital glaucoma. In: M Yanoff, JS Duker, JJ Augsburger, DT Azar, GR Diamond, JJ Dutton, D Miller, NA Rao, ES Rosen, AA Sadun, M Sherwood, J Sugar, JL Wiggs. Yanoff: Ophthalmology, 2nd ed.. St. Louis, MO: Mosby, Inc; 2004;
          2. Traboulsi EI. Malformations of the anterior segment of the eye. In: Traboulsi EI, ed. Genetic Diseases of the Eye. New York, NY. Oxford Publishing Press, Inc.; 1998:81-88..
          3. Traboulsi EI. A Compendium of Inherited Disorders and the Eye. New York, NY: Oxford University Press, Inc; 2006: 22-25..
          4. Irak-Dersu I. Secondary Congenital Glaucoma. Medscape. March 14, 2014; https://www.emedicine.com/oph/topic141.htm.
          5. Axenfeld-Rieger syndrome type 1. Online Mendelian Inheritance in Man (OMIM). 2017; https://www.ncbi.nlm.nih.gov/omim/180500.
          6. Axenfeld-Rieger syndrome. Genetics Home Reference. Genetics Home Reference: June 2012; https://ghr.nlm.nih.gov/condition/axenfeld-rieger-syndrome.
          7. Axenfeld-Rieger syndrome type 3. Online Mendelian Inheritance in Man (OMIM). 2017; https://www.ncbi.nlm.nih.gov/omim/602482.
          8. Axenfeld-Rieger syndrome type 2. Online Mendelian Inheritance in Man (OMIM). 2017; https://www.ncbi.nlm.nih.gov/omim/601499.
          9. Tümer Z & Bach-Holm D. Axenfeld–Rieger syndrome and spectrum of PITX2 and FOXC1 mutations. European Journal of Human Genetics. 10 de junio del 2009; 17:1527–1539. https://www.nature.com/ejhg/journal/v17/n12/full/ejhg200993a.html.
          10. Axenfeld-Rieger syndrome. Orphanet. 2011; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=782.

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