|55 Kenosia Avenue
Danbury, CT 06810
Toll Free: 1.800.999.6673
The National Organization for Rare Disorders (NORD) web site, its databases, and the contents thereof are copyrighted by NORD. No part of the NORD web site, databases, or the contents may be copied in any way, including but not limited to the following: electronically downloading, storing in a retrieval system, or redistributing for any commercial purposes without the express written permission of NORD. Permission is hereby granted to print one hard copy of the information on an individual disease for your personal use, provided that such content is in no way modified, and the credit for the source (NORD) and NORD’s copyright notice are included on the printed copy. Any other electronic reproduction or other printed versions is strictly prohibited.
The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.
Copyright 1991, 1997, 1998, 2006
Rieger syndrome is a rare genetic disorder characterized by absent or under-developed (hypodontia or partial adontia) teeth, mild craniofacial abnormalities, and various abnormalities of the eye, especially glaucoma. If unaccompanied by other signs and symptoms, the eye abnormalities are referred to as Rieger eye anomalies.
Specialists recognize two genetic forms of Rieger syndrome. Type I occurs as a result of mutations on chromosome 4 and Type II results from mutations on chromosome 13.
The main symptoms of Rieger syndrome are: eye anomalies including an underdeveloped iris, a small cornea (microcornea), an opaque ring around the outer edge of the cornea, adhesions in the front of the eye, and displacement of the pupil of the eye so that it is not centered; dental abnormalities including a congenital condition in which fewer teeth than normal (hypodontia) are present, a tooth or teeth that are smaller than normal (microdontia); and/or cone-shaped teeth.
Other characteristics include craniofacial abnormalities resulting in a face that appears to be flattened, with widely spaced eyes, a broad flat bridge of the nose, under-developed bones of the upper jaw (hypoplasia), and/or a protruding lower lip.
Some patients with Rieger syndrome may also present with an unusually small anal opening (anal stenosis); failure of the skin around the navel to decrease in size after birth, a condition that is sometimes mistaken for an umbilical hernia; and umbilical hernia, or protrusion of intestine through a weakness in the abdominal wall around the navel.
Glaucoma, or increased pressure within the eyeball, is sometimes present and can lead to blindness if not treated. This disease can result in damage to the optic disk and gradual loss of vision. The defects in the angle of the eye created by the iris and cornea (trabeculum), the vein at the corner of the eye that drains the water in the eye into the bloodstream (schlemm), and the adhesions associated with Rieger syndrome can lead to glaucoma
The following conditions have sometimes occurred in association with Rieger syndrome but researchers cannot agree as to whether they are separate entities or part of Rieger syndrome itself:
Myotonic dystrophy is a chronic progressive disease that causes atrophy of the muscles, failing vision, slurred speech, droopy eyelids and general muscle weakness. (For more information on this disorder choose "Myotonic Dystrophy" as your search term in the Rare Disease Database).
Conductive deafness is a type of hearing loss in which sound does not travel well to the inner ear.
Myotonia is a condition in which the muscles do not relax after contracting.
Mental retardation refers to less than average intellectual function with problems in learning and social behavior.
There are two forms of Rieger syndrome each of which is inherited as an autosomal dominant trait. The form known as Rieger syndrome type I is associated with a change (mutation) in a gene known as RIEG1 on chromosome 4 (4q25-q26). The second form, known as Rieger syndrome type II, has been mapped to gene map locus 13q14 and seems to represent a more complex form of the disorder. Patients with Rieger syndrome type II present with, in addition to the usual signs and symptoms, an enlarged head (hydrocephalus), cardiac defects, more hearing defects and kidney abnormalities.
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 4q25-q26" refers to a region between bands 25 and 26 on the long arm of chromosome 4. Chromosome 13q14 refers to a site at band 14 on the long arm of chromosome 13. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.
X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes but one of the X chromosomes is "turned off" and all of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is "turned off". A male has one X chromosome and if he inherits an X chromosome that contains a disease gene, he will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease, and a 25% chance to have an unaffected son.
X-linked dominant disorders are also caused by an abnormal gene on the X chromosome, but in these rare conditions, females with an abnormal gene are affected with the disease. Males with an abnormal gene are more severely affected than females, and many of these males do not survive.
Rieger syndrome is a rare disorder that affects males and females in about equal numbers. The eye defects associated with this disorder can be detected during the first month of life. When the eye defects are not visible, diagnosis may be delayed until early childhood when the eye and dental defects become apparent.
The following disorders may share similarities with Rieger syndrome:
Axenfeld-Rieger anomaly is a genetic disorder involving the eyes, ears and central nervous system. In this condition, the front of the iris may be entirely lacking or may be only partially present. The eye muscles may be absent or only partially available. The eyes are set unusually widely apart (hypertelorism) and may show signs of bulging (proptosis). Mild deafness is usually present due to improper development of the nerves in the ear (sensorineural deafness). Patients may be of short stature and in some cases show signs of an enlarged head (hydrocephalus) and mental retardation.
Cataract-dental syndrome is an extremely rare genetic disorder that may be evident at birth (congenital). It is primarily characterized by abnormalities of the teeth and clouding of the lens of the eyes (congenital cataracts), resulting in poor vision. Additional eye (ocular) abnormalities are also often present, such as unusual smallness of the front, clear portion of the eye through which light passes (microcornea) and involuntary, rapid, rhythmic eye movements (nystagmus). In some cases, the disorder may also be associated with additional physical abnormalities and/or mental retardation. The range and severity of symptoms may vary greatly from case to case, including among affected members of the same family.
Iris hypoplasia with glaucoma
An apparently X-linked recessive disorder has been reported in 2 and perhaps 3 families in Russia. From the findings in young family members, the atrophy or failure of growth of the iris seemed to be the primary condition and the glaucoma secondary. The similarity to Rieger anomaly, an autosomal dominant disorder, was noted by the physicians reporting.
Peters-plus syndrome is also known as Peters anomaly with short limb dwarfism. In its simplest form, the disorder is known as Peters congenital glaucoma. However, if it is also associated with dwarfism and mental retardation, plus disorders of the ear and cleft palate, the accumulation of signs is known as Peters-plus syndrome. Cataracts may also be present as well as mild facial distortion. Peters-plus syndrome is transmitted as an autosomal recessive disorder.
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.
Treatment of Rieger syndrome is symptomatic and supportive. Drug therapy is the primary treatment for glaucoma, usually consisting of eye drops. Laser surgery is usually reserved for those patients in whom the pressure in the eye is not relieved by medications. Prostheses (false teeth) are used for dental malformations. Genetic counseling may be of benefit for patients and their families.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.
For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
Murray JC, Semina EV. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:243-44.
Jones KL. Ed. Smith's Recognizable Patterns of Human Malformation. 5th ed. W. B. Saunders Co., Philadelphia, PA; 1997:592-93.
Gorlin RJ, Cohen MMJr, Levin LS. Eds. Syndromes of the Head and Neck. 3rd ed. Oxford University Press, London, UK; 1990:859-60.
Katz LA, Schultz RE, Semina EV, et al. Mutations in PITX2 may contribute to cases of omphalocele and VATER-like syndromes. Am J Med Genet A. 2004;130:277-83.
Brooks BP, Moroi SE, Downs CA, et al. A novel mutation in the PITX2 gene in a family with Axenfeld-Rieger syndrome. Ophthalmic Genet. 2004;25:57-62.
Wang Y, Zhao H, Zhang X, et al. Novel identification of a four-base-pair deletion mutation in PITX2 in a Rieger syndrome family. J Dent Res. 2003;82:1008-12.
Honkanen RA, Nishimura DY, Swiderski RE, et al. A family with Axenfeld-Rieger syndrome and Peters Anomaly caused by a point mutation (Phe112Ser) in the FOXC1 gene. Am J Ophthalmol. 2003;135:368-75.
Phillips JC. Four novel mutations in the PITX2 gene in patients with Axenfeld-Rieger syndrome. Ophthalmic Res. 2002;34:324-26.
Espinosa HM, Cox CJ, Semina EV, et al. A molecular basis for differential developmental anomalies in Axenfeld-Rieger syndrome. Hum Mol Genet. 2002;11:743-53.
FROM THE INTERNET
McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Rieger Syndrome, Type 1. Entry Number; 180500: Last Edit Date; 2/8/2005.
McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Rieger Syndrome, Type 2. Entry Number; 601499: Last Edit Date; 3/17/2004.
Sohrabi F. Rieger Syndrome. Center for Craniofacial Development and Disorders. Johns Hopkins University School of Medicine. February 20, 2004. 4pp.
Roche O. Rieger syndrome. Orphanet. July 2005. 2pp.
Rieger syndrome (RGS). Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes. Jablonski's Syndromes Database. nd. 4pp.
Report last updated: 2008/04/08 00:00:00 GMT+0