Duane retraction syndrome

Definition

Duane retraction syndrome is a congenital disorder that limits the movement of the eye. It may also involve other systems of the body.

Description

Duane retraction syndrome (DRS or DURS) is an inherited disorder characterized by a limited ability to move the eye to one side or the other. DRS is congenital, meaning that it is present at birth. It results from abnormal connections among the nerves that control the muscles of the eyes. About 80% of DRS cases involve one eye (uni-lateral) and about 20% involve both eyes (bilateral). Most unilateral DRS cases (72%) involve the left eye.

DRS was first described in 1905 by A. Duane. It also is known as: Duane syndrome (DUS)

• DR syndrome
• eye retraction syndrome
• retraction syndrome
• Stilling-Turk-Duane syndrome

DRS is one of a group of conditions known as strabismus, or misalignment of the eye. DRS is classified as an incomitant strabismus, because it is a misalignment of the eye that varies depending on the direction that the eye is gazing. It is further classified as an extraocular muscle fibrosis syndrome. This means that it is a condition associated with the muscles that move the eyes. Both the active and the passive movement of the eyeball are affected in DRS.

Physiology

DRS is believed to result from an abnormality that occurs during the development of the fetus in the womb. It may be caused by either environmental or genetic factors, or a combination of both. The developmental abnormality is believed to occur between the third and eighth weeks of fetal development. This is the period when the ocular muscles that rotate the eye, and the cranial nerves from the brain that control the ocular muscles, are forming in the fetus.

DRS appears to result from the absence of cranial nerve VI, which is known as the abducens nerve. The nerve cells in the brain that connect to the abducens nerve are also missing. The abducens nerve controls the lateral rectus muscle of the eye. This muscle moves one eye outward toward the ear, as a person looks toward that side. This movement is called abduction. In DRS, the nerves from a branch of cranial nerve III (the oculomotor nerve) also are abnormal. The oculomotor nerve controls several eye muscles, including the medial rectus muscle. This muscle moves the eye inward toward the nose, as the person looks toward the other side. This movement is called adduction.

The majority of individuals with DRS have limited or no ability to move an eye outward toward the ear. Instead, the opening between the eyelids of that eye widens and the eyeball protrudes. In addition, individuals with DRS may have only a limited ability to move the eye inward, toward the nose. Instead, when looking inward toward the nose, the medial and lateral recti muscles contract simultaneously. This causes the eyeball to retract, or pull into the skull, and causes the opening between the eyelids to narrow, as if one were squinting. Sometimes, the eye moves up or down as the individual attempts to look in toward the nose. This is called upshoot or downshoot, respectively.

In some individuals with DRS, the eyes may cross when looking straight ahead. Gazing straight ahead is called the primary position or primary gaze. Crossed eyes may cause the person to turn the head to one side or the other, to restore binocular vision. In such individuals, this "head turn" may become habitual.

Associated syndromes

About 30-50% of individuals with DRS have associated abnormalities. These may include additional eye problems, deafness, and nervous system or skeletal abnormalities. In particular, DRS may be associated with abnormalities in the upper extremities, especially the hands. Sometimes DRS is associated with Holt-Oram syndrome , a hereditary heart defect.

Okihiro syndrome is DRS in association with other abnormalities that may include: flatness in the normally-fleshy region between the thumb and the wrist (the thenar eminence) of one or both hands

• inability to flex the joint in the thumb
• hearing loss or deafness in one or both ears Okihiro syndrome also is known as:
• Duane syndrome with radial ray anomalies (as in the arms and hands)
• Duane/radial dysplasia syndrome (referring to abnormal tissue growth in the arms and hands)
• DR syndrome (the "D" refers to Duane anomaly and deafness; the "R" refers to radial and renal (kidney) dysplasia, or abnormal tissue growth in the arms, hands, and kidneys)
• Duane anomaly with radial ray abnormalities and deafness

Genetic profile

The genetic basis of DRS is unclear. The specific gene or genes that are responsible for DRS and the associated syndromes have not been identified. DRS may arise from a combination of environmental factors and defects in one or more genes.

Portions of several of the 23 pairs of human chromosomes may be associated with DRS. A gene that is involved in DRS has been localized to a region of chromosome 2. Deletions of portions of chromosomes 4 and 8 have also been associated with DRS. The presence of an additional small chromosome, thought to be broken off from chromosome 22, has been associated with DRS. It is possible that these chromosome rearrangements and abnormalities may account for the wide range of symptoms and syndromes that can occur with DRS.

The inheritance of DRS is autosomal, meaning that the trait is not carried on either the X or Y sex chromosomes. The most common type of DRS, DRS1, is inherited as an autosomal dominant trait. This means that only a single copy of a DRS gene, inherited from one parent, can result in the condition. The offspring of a parent with DRS is expected to have a 50% chance of inheriting the disorder. However, the autosomal dominant form of DRS sometimes skips a generation in the affected family; for example, a grandparent and grandchildren may have DRS, but the middle generation does not. Some forms of DRS may be recessive, requiring two copies of a gene, one inherited from each parent.

Family members may exhibit different types of DRS, indicating that the same genetic defect may be expressed by a range of symptoms. The severity of DRS also may vary among family members. Furthermore, the majority of individuals with DRS do not appear to have a family history of the disorder. There are very few reports of single families with a large number of affected individuals. However, close relatives of individuals with DRS often are affected by some of the other abnormalities that may be associated with the disorder.

Okihiro syndrome, or Duane syndrome with radial ray anomalies, and Holt-Oram syndrome both are inherited as autosomal dominant traits. However, like DRS, Okihiro syndrome may skip a generation in a family, or may be expressed by a range of symptoms within one family.

Demographics

DRS is estimated to affect 0.1% of the general population. It accounts for 1-5% of all eye movement disorders. Although it is not a sex-linked disorder, females are more likely than males to be affected by DRS (60% compared with 40%).

Signs and symptoms

Types of DRS

There are three generally-recognized types of DRS. Type 1 DRS (DRS1) accounts for about 70% of cases. With DRS1, abduction, the ability to move the eye toward the ear, is limited or absent. The eye widens and the eyeball protrudes when the eye is moved outward. In contrast, adduction, the ability to move the eye toward the nose, is normal or almost normal. However, the eye narrows and the eyeball retracts during adduction. The eyes of infants and children with DRS1 are usually straight ahead in the primary position. However, some children develop an increasing misalignment in the primary position and may compensate by turning their head.

With DRS type 2, adduction is limited or absent but abduction is normal, or only slightly limited. The eye narrows and the eyeball retracts during adduction. Type 2 accounts for approximately 7% of DRS cases.

With DRS Type 3, both abduction and adduction are limited. The eye narrows and the eyeball retracts during adduction. Type 3 accounts for about 15% of DRS cases.

Each type of DRS is subclassified, depending on the symptoms that occur when the individual is looking straight ahead (primary gaze). With subgroup A, the eye turns in toward the nose when gazing ahead. With sub-group B, the eye turns out toward the ear during a primary gaze. With subgroup C, the eyes are straight ahead in the primary position.

Associated symptoms

The majority of individuals with DRS are healthy and have no other symptoms. However, other body systems that may be affected with DRS include:

• skeleton
• ears and hearing
• additional involvement of the eyes
• nervous system

With Okihiro syndrome, the DRS can be unilateral or bilateral. In addition to a flatness at the base of the thumb, there may be difficulty with thumb movements. There also may be abnormalities or the complete absence of the radial and ulnar bones of the forearm. In extreme cases, the thumb or forearm may be absent. Okihiro syndrome may be accompanied by hearing loss, abnormal facial appearance, and heart, kidney, and spinal abnormalities.

Sometimes Wildervanck syndrome is associated with DRS. This syndrome may include congenital deafness and a fusion of the cervical (neck) vertebrae (C2 and C3).

Diagnosis

Diagnosis of DRS usually occurs by the age of ten. The clinical evaluation includes a complete family history, an eye examination, and examinations for other eye involvement or other physical abnormalities.

Eye examinations include the following measurements:

• visual acuity or sharpness
• alignment of the eyes
• range of motion of the eyes
• retraction (pulling in) of the eyeballs
• size of the eye opening between the eyelids
• upshoots and downshoots
• head turns

Hearing tests are frequently conducted. The cervical (neck) and thoracic (chest) parts of the spine, the vertebrae, the hands, and the roof of the mouth all are included in the examination as well.

Treatment and management

Special glasses with prisms can eliminate the head turning that is associated with DRS. Vision therapy may help with secondary vision problems.

Surgery may be performed for the following cosmetic reasons: abnormalities in the primary gaze (when looking straight ahead)

• an unusual compensatory head position
• a large upshoot or downshoot
• severe retraction of the eye The goal of surgery is to reduce or eliminate the misalignment of the eye that causes abnormal head turning, as well as to reduce the retraction of the eyeball and the upshoots and down-shoots. The surgery is directed at the affected muscles of the eye.

Children with DRS, as well as their siblings, require complete medical examinations to detect other abnormalities that may be associated with DRS.

Prognosis

If children with DRS go undiagnosed, a permanent loss of vision may occur. Surgical procedures may eliminate head turns and improve the misalignment of the eyes, particularly in the primary position. However, the absence of nerves for controlling the muscles of the eye cannot be corrected. Thus, no surgical procedure can completely eliminate the abnormal eye movements. However, the condition does not get worse during the course of one's life.

Resources

BOOKS

Engle, E. "The Genetics of Strabismus: Duane, Moebius, and Fibrosis Syndromes." In Genetic Diseases of the Eye: A Textbook and Atlas. Edited by E. Traboulsi, 477–512. New York: Oxford University Press, 1998.

PERIODICALS

Appukuttan, B., et al. "Localization of a Gene for Duane Retraction Syndrome to Chromosome 2q31." American Journal of Human Genetics 65 (1999): 1639–46.

Chung, M., J. T. Stout, and M. S. Borchert. "Clinical Diversity of Hereditary Duane's Retraction Syndrome." Ophthalmology 107 (2000): 500–03.

Evans, J.C., T. M. Frayling, S. Ellard, and N. J. Gutowski. "Confirmation of Linkage of Duane's Syndrome and Refinement of the Disease Locus to an 8.8-cM Interval on Chromosome 2q31." Human Genetics 106 (2000): 636–38.

ORGANIZATIONS

American Association for Pediatric Ophthalmology and Strabismus. <http://med-aapos.bu.edu/>.

Genetic Alliance. 4301 Connecticut Ave. NW, #404, Washington, DC 20008-2304. (800) 336-GENE (Helpline) or (202) 966-5557. Fax: (888) 394-3937. info@geneticalliance. <http://www.geneticalliance.org>.

March of Dimes Birth Defects Foundation. 1275 Mamaroneck Ave., White Plains, NY 10605. (888) 663-4637 or (914) 428-7100. [email protected]. <http://www.modimes.org>.

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

Schepens Eye Research Institute. 20 Staniford St., Boston, MA 02114-2500. (617) 912-0100. <http://www.eri.harvard.edu>.

WEBSITES

Cooper, Jeffrey. "Duane's Syndrome." All About Strabismus. Optometrists Network. 2001. (22 Apr. 2001). <http://www.strabismus.org/Duane_Syndrome.html>.

Duane's Retraction Syndrome. Yahoo! Groups. 2001. (22 Apr. 2001). <http://groups.yahoo.com/group/duanes>.

The Engle Laboratory. Research: Duane Syndrome. Children's Hospital Boston. (22 Apr. 2001). <http://www.tch.harvard.edu/research/engle/duane.html>.

Margaret Alic, PhD