Duane Syndrome

Updated: Dec 01, 2015
  • Author: Arun Verma, MD; Chief Editor: Hampton Roy, Sr, MD  more...
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Overview

Background

How do normal eye movements occur?

The 6 muscles that control the movement of the eye are attached to the outside of the wall of the eye. In each eye, there are 2 muscles that move the eye horizontally. The lateral rectus muscle pulls the eye out toward the ear and the medial rectus muscle pulls the eye in toward the nose. Four other muscles move the eye up or down and at an angle. Each eye muscle receives the command for movement from cranial nerves that exit the brain.

What is Duane syndrome?

Duane syndrome (DS) is a rare, congenital disorder of eye movement. In most patients, DS is diagnosed by the age of 10 years.

DS is a miswiring of the eye muscles that causes some eye muscles to contract when they should not and other eye muscles not to contract when they should. People with DS have a limited and sometimes absent ability to move their eye outward toward the ear (ie, abduction), and in most cases, they have a limited ability to move the eye inward toward the nose (ie, adduction).

Duane syndrome. Duane syndrome.

This probably occurs around the sixth week of pregnancy and is due to poor development of tiny parts of the brainstem that control the eye muscles. In DS, the sixth cranial nerve that controls the lateral rectus muscle (the muscle that rotates the eye out toward the ear) does not develop properly. Why the nerve does not develop is not yet understood. Thus, the problem is not primarily with the eye muscle itself but with the nerve that transmits the electrical impulses to the muscle. There is also irregular innervation of a branch from the third cranial nerve, which controls the medial rectus muscle (the muscle that rotates the eye toward the nose). This is why abnormalities may be found in both left gaze and right gaze.

Often, when the eye moves toward the nose, the eyeball also pulls into the socket (ie, retraction), and the eye opening narrows. In some cases, the eye moves upward or downward. Many patients with DS develop a habit of turning their face to maintain binocular vision and thus compensate for improper turning of the eyes. In about 80% of all cases of DS, only 1 eye is affected, most often the left eye. However, in some cases, both eyes are affected; usually, 1 eye is affected more than the other. See the image below.

An individual diagnosed with Duane syndrome in the An individual diagnosed with Duane syndrome in the left eye. In this image, the affected person is attempting to look far right. Notice the afflicted left eye faces straight and up (an "upshoot"), rather than following the right eye to the right.

In 70% of patients, DS is the only disorder the individual has. However, other conditions and syndromes have been associated with DS. These include malformation of the skeleton, ears, eyes, kidneys, and nervous system, as well as the following: Okihiro syndrome (an association of DS with forearm malformation and hearing loss), Wildervanck syndrome (fusion of neck vertebrae and hearing loss), Holt-Oram syndrome (abnormalities of the upper limbs and heart), morning-glory syndrome (abnormalities of the optic disc or blind spot), and Goldenhar syndrome (malformation of the jaw, cheek, and ear, usually on 1 side of the face).

What is Duane retraction syndrome?

Sinclair (in 1895), Bahr (in 1896), Stilling (in 1887), Turk (in 1899), and Wolff (in 1900) first described Duane retraction syndrome (DRS). [1, 2, 3, 4, 5] In 1905, Duane reported 54 cases, summarizing all the clinical findings, reviewing previous work, and offering theories on the pathogenesis and treatment of the disease. [6] See the image below.

Duane syndrome. Duane syndrome.

Brown classified the condition into 3 subtypes, based upon clinical observations. [7] Type A corresponded to limited abduction and less limited adduction (as described originally by Duane). Type B corresponded to limited abduction but normal adduction. Type C corresponded to limitation of adduction that is greater than limitation of abduction, giving rise to a divergent deviation and a head posture in which the face is turned away from the side of the affected eye.

In 1974, with the support of electromyography (EMG) and following the suggestions of Lyle and Malbran, Huber classified DRS into the 3 types: Duane 1, Duane 2, and Duane 3. [8, 9, 10] Type 1 is marked limitation of abduction (corresponds to Type B in Brown's classification) explicable by maximum innervation reaching the lateral rectus muscle only when the affected eye is adducted. Type 2 is limitation of adduction (corresponds to Type C in Brown’s classification), which Huber explains as being caused by co-innervation of both medial and lateral rectus muscles on attempted adduction. Type 3 is limitation of both adduction and abduction (corresponds to Type A in Brown’s classification), which Huber explains as being due to co-contraction, accompanied by a loss of innervation to the lateral rectus muscle on attempted abduction.

DS is a congenital ocular motility disorder characterized by limited abduction and/or limited adduction. The palpebral fissure narrows (ie, the globe retracts) on attempted adduction. Upward or downward deviation may occur with attempted adduction because of a leash effect. Often associated with this condition is a tether phenomenon consisting of overelevation, overdepression, or both during adduction as the retracted globe escapes from its horizontal rectus restrictions. It is a condition of aberrant innervation that results in co-contraction of the medial and lateral recti in the affected eye. Therefore, DS can be considered to be congenital miswiring of the medial and the lateral rectus muscles such that globe retraction occurs on adduction.

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Pathophysiology

Neuropathologic, neuroradiologic, and neurophysiologic data

Findings from neuropathologic, neuroradiologic, and neurophysiologic studies support the hypothesis that DS results from an absence of cranial nerve VI (abducens nerve). Neuropathologic evidence comes from postmortem examinations of individuals who had DS. These studies have shown an absence of cranial nerve VI and its corresponding alpha motor neurons in the pons, as well as aberrant innervation of the lateral rectus muscle by a branch of cranial nerve III.

MRI studies of an individual with DS also revealed the absence of the abducens nerve. Neurophysiologic evidence of neuronal involvement in DS is derived from EMG studies, which show that the medial and lateral recti muscles are electrically active in individuals with DS. However, when individuals with DS attempt to move their eyes inward (ie, adduct it), both of these muscles contract at the same time, causing the eyeball to retract inward and the eye opening (palpebral fissure) to become narrowed. These findings support aberrant innervation of the lateral rectus muscle.

Autopsy specimens have shown agenesis of the sixth nerve nucleus and innervation of the lateral rectus muscle by the third nerve nucleus. This observation explains the globe retraction on attempted adduction. In neuropathologic terms, the cause of DS is an absent sixth nerve nucleus and innervation of the lateral rectus by a branch of the inferior division of the third nerve.

Condensation of the mesoderm around the eye results in development of the extrinsic eye muscles. When the embryo is 7 mm long, they form 1 mass, which is supplied by only the third nerve. When the embryo is 8-12 mm long, that is, when the fourth nerve and the sixth nerve arrive, this mass divides into separate muscles. Because of an absence of or an aplasia of the abducens nerve, a branch of the oculomotor nerve (as a substitute) conceivably enters the part of the muscle mass that is to become the lateral rectus muscle.

Given the evidence that DS results from an absence of the abducens nerve (cranial nerve VI) and that DS is associated with other anomalies in some cases, DS is thought to reflect a disturbance of normal embryonic development. Either a genetic factor or an environmental factor may be involved when the cranial nerves and ocular muscles are developing at 3-8 weeks of gestation.

The association of DS with other ocular anomalies and congenital facial, skeletal, or neural abnormalities in 30-50% of patients further substantiates the hypothesis of disturbed embryogenesis. A teratogenic event during the second month of gestation seems to cause most ocular and extraocular abnormalities observed in combination with DS. DRS is present from birth, even if it is not recognized during infancy. An abnormal head posture and strabismus are often visible in old photographs taken in early childhood.

Genetic and environmental factors

The genetic basis of DS is being studied, but genetic loci for DS have not. Similar to congenital fibrosis of the extraocular muscles (CFEOM), DS is classified as strabismus, under the subclassification of incomitant strabismus and extraocular muscle fibrosis syndromes. Although the term muscle fibrosis suggests that syndromes under this heading are primary disorders of muscle, evidence suggests that DS (and other syndromes under this heading, including CFEOM) may be primary disorders of nerve innervation. A review of fibrosis syndromes can be found in Engle's article in 1998. [11]

Both genetic factors and environmental factors are likely to play a role in the development of DS. Most cases of DS cases are sporadic, with only approximately 2-5% of patients having a familial pattern; families with large involvement are rarely reported. Both dominant forms and recessive forms of DS have been documented. In some families with dominant DS, the disease skips a generation (reduced penetrance) and ranges in severity (variable expressivity). Most familial cases are not associated with other anomalies.

Genetic linkage studies of a large family with DS established the location of a DS gene on chromosome 2. Although a genetic cause of DS has long been accepted, these studies were the first to show a statistically significant linkage. In addition, cytogenetic results of individuals with DS have shown, in rare cases, abnormalities that suggest the contribution of more than 1 gene. Deletions on chromosomes 4 and 8 and an extra marker chromosome thought to be derived from chromosome 22 have been documented in individuals with DS.

Familial occurrence with dominant inheritance patterns has been reported. DS has also been described in monozygotic twins. However, most cases are sporadic rather than familial. Pairs of identical twins with mirror-image DS have been described. Its most common variant (type 1, 85%) and most commonly manifests in the left eye (60%) and in girls (60%) as severely limited or absent abduction. In 90% of cases, the patient has no family history of DS. Ten percent of patients will have an affected family member, and these tend to be cases where both eyes are involved. There is currently no test that can determine whether a patient has a hereditary form.

In a demographical and clinical profile based on 441 cases, Kekunnaya et al concluded that unilateral and bilateral DRS show considerable differences in gender distribution, associated ocular deviation, overshoots, and ocular and systemic associations. [12]

See also the Causes section.

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Epidemiology

Frequency

United States

The frequency of DS in the general population of individuals with eye movement disorders (strabismus) is approximately 1-5%. The most common clinical presentation is type 1 DS (70-80%) followed by type 2 (7%) and type 3 (15%). Involvement of both eyes is less common than involvement of 1 eye only. Approximately 80% of cases are unilateral. Of the unilateral cases, the left eye is most often affected (60-72%).

See also the International section.

International

DS accounts for 1% of all cases of strabismus. Unilateral retraction syndrome is the rule; the left eye is distinctly involved in 60% of cases, the right eye is involved in 20% of cases, and both eyes are involved in 20% of cases.

Mortality/Morbidity

About 40% of patients develop esotropia and tight medial rectus muscles; therefore, they adopt a head turn toward the eye to maintain single binocular vision, or they maintain a straight head but accept esotropia, abnormal retinal correspondence (ARC), and suppression, if available.

In about 30% of patients, compensatory head positions are necessary to achieve binocular single vision. Before surgery is contemplated, coexisting and clinically significant refractive errors, anisometropia, and amblyopia must be treated. Kirkham found that amblyopia was present in 21% of his patients with DRS, and nearly 50% had anisometropia. [13] In 2 large series, the incidence of amblyopia in DRS patients was 10% and 14%, respectively. However, Maruo and coworkers found a 3.6% prevalence of amblyopia among 220 patients with DRS. [14] Tredici and von Noorden also reported a 3% incidence of amblyopia in 72 patients and commented that this incidence is similar to that in the general population. [15, 16]

Race

No racial preference is reported.

Sex

The female-to-male ratio is 3:2, but this female predominance is not explained.

Age

This syndrome is a congenital anomaly. Most cases are diagnosed by the age of 10 years.

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Prognosis

 

Duane retraction syndrome (DRS) represents a spectrum of motility disorders in which the common feature is retraction of the affected eye on attempted adduction. Electrophysiologic and neuropathologic studies have shown that the underlying cause is anomalous innervation of the lateral rectus with the medial rectus and, at times, with vertical muscles in the affected eye. Clinical abnormalities observed in DRS can include any or all of the following: a deviation in the primary position; abnormal head position; severe retraction causing a pseudoptosis; and upshoots and/or downshoots associated with A, V, or X patterns. A surgical approach based on the analysis of these four features is presented, allowing the surgeon to devise an appropriate, individualized plan for a given case, which can yield optimal results in one operation.

This disorder consists of deficient horizontal eye movements, eyelid retraction, palpebral fissure narrowing, and abnormal vertical eye movements. Most cases are sporadic and unilateral (usually left side) with a slight female predominance. Several associated ocular and systemic conditions have been described in patients with DRS. In most cases, the abducens nucleus and nerve are absent or hypoplastic, and the lateral rectus muscle is innervated by a branch of the oculomotor nerve. However, there may be contributing mechanical abnormalities. Type I DRS (primary gaze position esotropia with limitation of abduction) comprises most cases. Approximately 50% of patients with type I DRS are orthophoric in primary gaze. Esotropia is the most common type of strabismus encountered, and characteristic upshoots and downshoots occur in adduction. Surgical intervention has gradually become more popular in order to improve the primary gaze alignment and mitigate some of the associated abnormalities in ocular motility. However, patients are rarely rendered clinically healthy, and limited expectations are appropriate.

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