Rieger Syndrome

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Rieger syndrome

Definition

Rieger syndrome is a rare disorder characterized by absence and/or malformation of certain teeth, mild craniofacial (relating to the head and the face) abnormalities, and various eye abnormalities. The eye abnormalities, referred to as Rieger eye malformations, may be present separately or as a part of Rieger syndrome.

Description

First characterized by Herwigh Rieger, an Austrian ophthalmologist in 1935, Rieger syndrome is a dominantly inherited disease. Disease expression is highly variable, including craniofacial, ocular, and dental malformations. Symptoms may also include myotonic dystrophy (a condition characterized by delay in the ability to relax muscles), umbilical abnormalities (abnormalities relating to where the umbilical cord attaches to a baby), and other defects. Psychomotor retardation, a slowing of the motor action directly proceeding from mental activity, occurs in some cases.

Rieger syndrome is also sometimes referred to as goniodysgenesis hypodontia, iridogoniodysgenesis with somatic anomalies, or RGS. It is a multiple congenital anomaly syndrome, a syndrome marked by multiple abnormalities at birth. Currently, there are two genetic types of Rieger syndrome identified. Type I results from a mutation on chromosome 4 and Type II on chromosome 13.

Genetic profile

Rieger syndrome is inherited as an autosomal dominant disease. In autosomal dominant inheritance , a single abnormal gene on one of the autosomal chromosomes (one of the first 22 non-sex chromosomes) from either parent can cause the disease. One of the parents will have the disease (since it is dominant) and is the carrier. Only one parent needs to be a carrier in order for the child to inherit the disease. A child who has one parent with the disease has a 50% chance of also having the disease.

There is evidence that there is more than one genetic form of Rieger syndrome. The disease gene responsible for Rieger syndrome Type I is caused by mutations in the RIEG1 gene, which is located on the long arm (q) of chromosome 4 (4q25-Q26).

Linkage studies have indicated that a second type of Rieger syndrome, Type II, maps to the long arm of chromosome 13, at 13q14 (gene RIEG2).

Demographics

Rieger syndrome is very rare. Little is known in regard to the number of affected individuals or whether certain areas or ethnic groups are at a greater risk. Since the disease appears to be inherited in an autosomal dominant manner, meaning that it is transmitted on one of the non-sex chromosomes, males and females have an equal chance of acquiring the abnormal gene from their parents.

Signs and symptoms

The symptoms of Rieger syndrome are expressed variably. The main symptoms of Rieger syndrome are:

Ocular malformations, called Rieger eye malformations, include underdeveloped iris, a small cornea (microcornea), an opaque ring around the outer edge of the cornea, adhesions (abnormal union of surfaces normally separate) in the front of the eye, and/or displacement of the pupil of the eye so that it is not centered.
Dental abnormalities include a congenital condition causing a fewer number of teeth than normal (hypodontia); a condition in which a single tooth, pairs of teeth, or all the teeth are smaller than normal (microdontia), and/or cone-shaped.
Craniofacial abnormalities include a protruding lower lip, a broad, flat bridge of the nose, and/or underdeveloped bones of the upper jaw (hypoplasia) causing the face to have a flat appearance.

Other conditions that have been found in some patients with Rieger syndrome are:

Anal stenosis (a small anal opening).
Failure of the skin around the navel to decrease in size after birth.
Protrusion of intestine through a weakness in the abdominal wall around the navel (umbilical hernia).
Glaucoma (increased pressure within the eyeball) may result from the ocular malformations associated with Rieger syndrome, including defects in the angle of the eye that is 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 associated adhesions. Glaucoma can result in damage to the optic disk and gradual loss of vision, causing blindness in approximately 50% of affected individuals.

Additional conditions have sometimes occurred in conjunction with Rieger syndrome. Whether they are separate entities in which the Rieger eye malformations are present or part of Rieger syndrome is not determined. These conditions are:

Myotonia (a condition in which the muscles do not relax after contracting).
Myotonic dystrophy (a chronic progressive disease causing muscles to atrophy, slurred speech, failing vision, droopy eyelids, and general muscle weakness).
Conductive deafness (hearing loss in which sound does not travel well to the inner ear).
Less than average intellectual function associated with problems in learning and social behavior.

Diagnosis

This disorder can be detected soon after birth if the eye defects are visible. When the eye defects are not visible during the first month of life, Rieger syndrome is usually detected in early childhood when the eye and dental defects become apparent.

Molecular genetic testing for the RIEG1 and RIEG2 genes is not generally available. But since the molecular structure of the genes has been identified, the possibility now exists for DNA-based testing for diagnosis and genetic counseling .

Genetic counseling

Genetic counseling may be beneficial for patients and their families. Only one parent needs to be a carrier in order for the child to inherit the disease. A child has a 50% chance of having the disease if one parent is diagnosed with the disease and a 75% chance of having the disease if both parents have Rieger syndrome.

Prenatal testing

For couples known to be at risk for having a baby with Rieger syndrome, testing may be available to assist in prenatal diagnosis. Prior testing of family members is usually necessary for prenatal testing.

Either chorionic villus sampling (CVS) or amniocentesis may be performed for prenatal testing. CVS is a procedure to obtain a small sample of placental tissue, called chorionic villi tissue, for testing. Examination of fetal tissue can reveal information about the defects that leads Rieger syndrome. Chorionic villus sampling can be performed at 10–12 weeks gestation.

Amniocentesis is a procedure that involves inserting a thin needle into the uterus and the amniotic sac, and withdrawing a small amount of amniotic fluid. DNA can be extracted from the fetal cells contained in the amniotic fluid and tested. Amniocentesis is performed at 16–18 weeks gestation.

Tissue showing the gene mutation for Rieger syndrome Type I or II obtained from CVS or in amniotic fluid is diagnostic.

Related disorders

A number of disorders are similar to Rieger syndrome. Comparisons may be useful for a differential diagnosis. These related disorders include:

Cat-eye syndrome, a rare disorder marked by a cleft along the eyeball affecting the iris, the membrane that covers the white of the eyeball (choroid), and/or the retina and causing a vertical pupil; abnormalities such as small polyps or pits near the front of the outer ear; and absence of the opening, duct, or canal of the anus. Other symptoms may include mild mental deficiency and heart defects.
Ectodermal dysplasias, a group of hereditary syndromes affecting the skin, its derivatives, and some other organs. Symptoms include predisposition to respiratory infection, eczema, poorly functioning sweat glands, abnormal hair and nails, and difficulties with the nasal passages and ear canals.
Eye, anterior segment dysgenesis, a rare congenital disorder resulting in abnormal tissue development of the outer eye segment. In less severe cases, the back of the outer surface of the cornea is nontransparent (embryotoxin). Symptoms include ocular abnormalities and malformations of the teeth, abdominal wall, skeleton, and heart.

It is generally thought that Axenfeld anomaly, marked by defects limited to the outer part of the field of vision of the eye, should not be considered a separate entity of Rieger syndrome.

Treatment and management

A physician familiar with the range of problems seen in individuals with Rieger syndrome is important for appropriate health supervision. Treatment should include assistance finding support resources for the family and the individual with Rieger syndrome.

Treatment of Rieger syndrome is focused on treating the symptoms expressed. Depending on what they are, these treatments may include:

Drug therapy for glaucoma, usually a topical beta blocker in the form of eye drops. Laser surgery may be performed on those patients in whom the pressure in the eye is not relieved by medications.
Prostheses (false teeth) or other orthodontic interventions for dental malformations.
Other surgical management of congenital anomalies includes repair of an umbilical hernia that does not close by itself and plastic surgery for craniofacial abnormalities.

Prognosis

Prognosis depends upon the severity of the disease. Eye defects may lead to severly impaired vision or blindness. Rieger syndrome does not generally lead to a shortened life span.

Resources

BOOKS

Jorde, Lynn B., et al., eds. Medical Genetics. 2nd ed. St. Louis: Mosby, 1999.

PERIODICALS

Alward, W. L. "Axenfeld-Rieger syndrome in the age of molecular genetics." American Journal of Ophthalmology 130 (2000): 107–15.

Amendt, B. A., E. V. Semina, and W. L. Alward. "Rieger syndrome: a clinical, molecular, and biochemical analysis." Cellular and Molecular Life Sciences 11 (2000): 1652–66.

Craig, J. E., and D. A. Mackey. "Glaucoma genetics: Where are we? Where will we go?" Current Opinions in Ophthalmology 10 (1999): 126–34.

ORGANIZATIONS

Blind Children's Fund. 4740 Okemos Rd., Okemos, MI 48864-1637. (517) 347-1357. <http://www.blindchildrensfund.org>.

National Association for Parents of the Visually Impaired. PO Box 317, Watertown, MA 02472. (617) 972-7441 or (800) 562-6265. <http://www.spedex.com/napvi>.

National Association for Visually Handicapped. 22 West 21st Street, New York, NY 10010. (212) 889-3141. <http://www.navh.org>.

National Eye Institute. Bldg. 31 Rm 6A32, 31 Center Dr., MSC 2510, Bethesda, MD 20892-2510. (301) 496-5248. [email protected]. <http://www.nei.nih.gov>.

National Foundation for Ectodermal Dysplasias. PO Box 114, 410 East Main St., Mascoutah, IL 62258-0114. (618) 566-2020. Fax: (618) 566-4718. <http://www.nfed.org>.

National Organization for Rare Disorders (NORD). PO Box 8923, New Fairfield, CT 06812-8923. (203) 746-6518 or (800) 999-6673. Fax: (203) 746-6481. <http://www.rarediseases.org>.

Vision Community Services. 23 A Elm St., Watertown, MA 02472. (617) 926-4232 or (800) 852-3029. <http://www.mablind.org>.