Duane Syndrome 

Updated: Jun 19, 2019
Author: Arun Verma, MD; Chief Editor: Hampton Roy, Sr, MD 

Overview

Practice Essentials

Duane syndrome (DS), or Duane retraction (or co-contraction) syndrome (DRS), is a congenital restrictive strabismus that can occur either as an isolated entity or in conjunction with other congenital anomalies. It is now listed as a congenital cranial dysinnervation disorder. It is characterized by co-contraction of horizontal recti upon attempted adduction, causing globe retraction along with variable amounts of upshoots or downshoots. It may have limited abduction or adduction or both and presents as esotropic, exotropic, or orthotropic Duane.

The diagnosis of this disease is usually clinical. However, recent research has provided a greater insight into the genetic basis of this disease, paving a way for a greater role of genetics in diagnosis and management. This disease can have a variable presentation; hence, the treatment plan should be tailored to each patient.

Background

Duane syndrome is a rare, congenital disorder of eye movement. Most individuals with Duane syndrome are diagnosed by age 10 years.

Normal eye movements

The six muscles that control eye movement are attached to the outside of the wall of the eye. In each eye, two muscles 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.

Duane syndrome

Duane syndrome (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 Duane syndrome 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 Duane syndrome, 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 Duane syndrome 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 Duane syndrome, only one eye is affected, most often the left eye. However, in some cases, both eyes are affected; usually, one 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 cases, Duane syndrome is an isolated condition. However, other conditions and syndromes have been associated with Duane syndrome. These include malformation of the skeleton, ears, eyes, kidneys, and nervous system, as well as the following:

  • Okihiro syndrome (an association of Duane syndrome 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)
  • Goldenhar syndrome (malformation of the jaw, cheek, and ear, usually on one side of the face)

History of Duane 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 Duane syndrome 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.

Duane syndrome 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, Duane syndrome can be considered to be congenital miswiring of the medial and the lateral rectus muscles such that globe retraction occurs on adduction.

Pathophysiology

Neuropathologic, neuroradiologic, and neurophysiologic data

Findings from neuropathologic, neuroradiologic, and neurophysiologic studies support the hypothesis that Duane syndrome results from an absence of cranial nerve VI (abducens nerve). Neuropathologic evidence comes from postmortem examinations of individuals who had Duane syndrome. 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 Duane syndrome also revealed the absence of the abducens nerve. Neurophysiologic evidence of neuronal involvement in Duane syndrome is derived from EMG studies, which show that the medial and lateral recti muscles are electrically active in individuals with Duane syndrome. However, when individuals with Duane syndrome 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 Duane syndrome 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 Duane syndrome results from an absence of the abducens nerve (cranial nerve VI) and that Duane syndrome is associated with other anomalies in some cases, Duane syndrome 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 Duane syndrome 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 Duane syndrome. Duane syndrome 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 Duane syndrome is being studied, but genetic loci for Duane syndrome have not. Similar to congenital fibrosis of the extraocular muscles (CFEOM), Duane syndrome 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 Duane syndrome (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 Duane syndrome. Most cases of Duane syndrome 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 Duane syndrome have been documented. In some families with dominant Duane syndrome, 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 Duane syndrome established the location of a Duane syndrome gene on chromosome 2. Although a genetic cause of Duane syndrome has long been accepted, these studies were the first to show a statistically significant linkage. In addition, cytogenetic results of individuals with Duane syndrome 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 Duane syndrome.

Familial occurrence with dominant inheritance patterns has been reported. Duane syndrome has also been described in monozygotic twins. However, most cases are sporadic rather than familial. Pairs of identical twins with mirror-image Duane syndrome 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 Duane syndrome. 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 Duane syndrome show considerable differences in gender distribution, associated ocular deviation, overshoots, and ocular and systemic associations.[12]

See also the Causes section.

Epidemiology

Frequency

United States

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

International

Duane syndrome 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 with Duane syndrome 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 Duane syndrome, and nearly 50% had anisometropia.[13] In 2 large series, the incidence of amblyopia in patients with Duane syndrome was 10% and 14%, respectively. However, Maruo and coworkers found a 3.6% prevalence of amblyopia among 220 patients with Duane syndrome.[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

Duane syndrome has no reported racial preference.

Sex

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

Age

Duane syndrome is a congenital anomaly. Most cases are diagnosed by age 10 years.

Prognosis

Duane syndrome 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 Duane syndrome 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 Duane syndrome. 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 Duane syndrome (primary gaze position esotropia with limitation of abduction) comprises most cases. Approximately 50% of patients with type I Duane syndrome 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.

The prognosis of surgery is not good; therefore, it is best to avoid surgery if patients have some form of binocular vision.

Patient Education

Patients must be taught to learn some form of head tilt and orthoptic training to have some binocular vision.

 

Presentation

History

Patients with Duane syndrome (DS) can present with a history of the following:

  • Strabismus
  • Head tilt
  • Loss of binocular vision
  • Reduced abduction
  • Picture of paralytic squint

Physical

Duane syndrome can be isolated, or it can be associated with other congenital anomalies. Duane syndrome is an isolated finding in approximately 70% of patients, but it may be associated with other malformations. Major anomalies associated with Duane syndrome can be grouped into 4 categories: skeletal, auricular, ocular, or neural. Duane syndrome can also be associated with other well-defined syndromes, including Okihiro syndrome, Wildervanck syndrome, Holt-Oram syndrome, morning-glory syndrome, and Goldenhar syndrome.

Duane syndrome can be associated with both ocular anomalies and systemic anomalies. Ocular anomalies commonly associated with Duane syndrome include dysplasia of the iris stroma, pupillary anomalies, cataracts, heterochromia, Marcus Gunn jaw-winking, coloboma, crocodile tears, and microphthalmos. Systemic anomalies include Goldenhar syndrome, Klippel-Feil anomalad, and congenital labyrinthine deafness.

Most cases are sporadic. The congenital anomaly consists of absence of the abducens nerve nucleus in the brainstem and simultaneous innervation of the affected lateral rectus muscle by the inferior branch of the oculomotor nerve. The left eye is involved in 60% of cases. Duane syndrome is often bilateral but asymmetrical.

Clinical types

Duane syndrome is often clinically divided into 3 types (see the Table below). Different clinical types may be present within the same family; this occurrence suggests that the same genetic defect may produce a range of clinical presentations. The clinical spectrum of different types of Duane syndrome result from the variability of the 3 innervational portions of the lateral rectus muscle, namely, the normal abducens innervated portion, the abnormal oculomotor innervated portion, and the noninnervated fibrotic portion.

In Duane syndrome type 1, the ability to move the affected eye outward toward the ear (abduction) is limited, but the ability to move the affected eye inward toward the nose (adduction) is normal or nearly so. The palpebral fissure narrows, and the eyeball retracts into the orbit when the patient looks inward toward the nose (adduction). When he or she looks outward toward the ear (abduction), the reverse occurs.

In Duane syndrome type 2, adduction of the affected eye is limited, whereas abduction of the eye is normal or only slightly limited. The palpebral fissure narrows, and the eyeball retracts into the globe when the affected eye attempts to adduct.

In Duane syndrome type 3, adduction and abduction of the affected eye is limited. The palpebral fissure narrows, and the eyeball retracts when the affected eye attempts to adduct.

These 3 types can be further classified into 3 subgroups designated A, B, and C to describe the eyes when looking straight (in primary gaze). In subgroup A, the affected eye is turned inward toward the nose (esotropia). In subgroup B, the affected eye is turned outward toward the ear (exotropia). In subgroup C, the eyes are in a straight primary position.

Table 1. Types of Duane Syndrome. (Open Table in a new window)

Category

Description

Type

1 (70%-80%)

Inability to abduct

Normal or minimal defect in adduction

Esotropia with head straight

A or V pattern

Usually updrift or a downdrift of affected eye on adduction or attempted abduction

Globe retraction and palpebral-fissure narrowing on adduction

Usual face turn to affected side

Normal stereo possible

2 (about 7%)

Inability to adduct

Normal or minimal defect in abduction

Exotropia of the affected eye

Marked upshoot

Globe retraction and palpebral-fissure narrowing on adduction

Stereo normal or suppressed

Face turn to normal side

3 (about 15%)

Inability ability to abduct and adduct

Globe retraction and palpebral-fissure narrowing on attempted adduction

Possible upshoot and downshoot on adduction

Straight or nearly straight head position

Usually, normal stereo

4

Not usual Duane syndrome or Duane syndrome-type appearance

Large-angle exotropia

Face turn to uninvolved side

Limited adduction

Simultaneous abduction when looking toward uninvolved side

Usually suppresses 1 eye

Subtype

A

Affected eye turned inward toward the nose (esotropia)

B

Affected eye turned outward toward the ear (exotropia)

C

Eyes in a straight primary position

Clinical manifestations

The aberrant innervation produces several manifestations. These manifestations include a face turn with strabismus in primary position, an upshoot or downshoot during adduction, a vertical deviation in primary position, retraction during adduction, and enophthalmos.

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.

On occasion, fusion is impossible in a patient with Duane syndrome, usually because bilateral involvement or a vertical deviation precludes fusion with any head posture.

Duane syndrome is characterized in its typical and most frequently observed form by abduction deficiency, globe retraction and palpebral fissure narrowing on attempted adduction, widening of the palpebral fissure on attempted abduction, and normal or only slightly defective adduction.

Sensory adaptation

Most patients with sensory adaptation demonstrate a peculiar sensory adaptation with excellent binocular functions in directions of gaze where visual axes are aligned and usually suppression without diplopia in the field of the paretic muscles.

Some suggest that the second image is ignored, rather than suppressed, in view of the difficulties encountered in plotting the suppression scotoma.

Signs

Signs of Duane syndrome include the following:

  • Head turn to maintain fusion (about 66% of cases, 76% of unilateral cases)
  • Strabismus (about 77% of cases)
  • Globe retraction
  • Palpebral fissure narrowing
  • Anisometropia and/or amblyopia (though not more prevalent than in the general population)
  • Heterochromia
  • Iris dysplasia
  • Ptosis
  • Nystagmus
  • Choroidal coloboma
  • Hypoplasia of the optic nerve

Clinical evaluation

A thorough family history and an ocular examination are conducted, with special attention to other ocular or systemic malformations. Measurements of visual acuity, ocular misalignment, ocular range of motion, head turn, globe retraction, size of the palpebral fissure size, and upshoots and downshoots are indicated. In addition, an examination of the cervical and thoracic spine, palate, vertebrae, hands, and hearing is recommended to rule out disorders associated with Duane syndrome.

Differential diagnosis and other problems to be considered

One type of inherited Duane syndrome that is associated with other birth defects is Duane syndrome with radial-ray anomalies. The association of Duane syndrome with radial-ray anomalies is referred as Duane/radial dysplasia syndrome, DR syndrome (acronym for Duane anomaly, deafness, radial dysplasia, renal dysplasia), and Okihiro syndrome.

The familial association of Duane syndrome with radial-ray anomalies appears to be autosomal dominant with incomplete penetrance and variable expressivity. Duane syndrome can be unilateral or bilateral. Radial dysplasia can range from hypoplasia of the thenar eminence (base of the thumb) with or without thumb abduction and apposition weakness, hypoplasia or absence of the thumb, and hypoplasia or absence of the radial and ulnar bones to an absent forearm. Hearing loss, dysmorphic facies and cardiac, renal, and vertebral anomalies are variably expressed in some families. The chromosomal location of the gene for this syndrome is unknown, but families are being enrolled to identify the gene or genes involved in this condition.

Other diagnostic considerations include medial-wall fracture with incarceration of orbit contents might be a consideration; retraction of globe with attempted abduction is seen on examination. Retraction of convergent nonfixating eye with associated loss of conjugate lateral gaze and occurrence of the near reflex on attempted lateral gaze might also be considered. Because Duane syndrome mimics sixth nerve paresis, the differential diagnoses can be similar to those described for sixth nerve paresis.

In 1977, Duane and coauthors described entirely unrelated pseudo-Duane syndrome in which abduction is restricted and narrowing of the palpebral fissure and retraction of the globe occur after fracture of the medial orbital wall with entrapment of the medial rectus muscle.[17]

Causes

Duane syndrome is thought to be a miswiring of the medial and the lateral rectus muscles, or the muscles that move the eyes. Also, patients with Duane syndrome lack the abducens nerve, or the sixth cranial nerve, which is involved in eye movement. However, the etiology or origin of these malfunctions remains a mystery. Many researchers believe that Duane syndrome results from a disturbance due to either genetic factors or environmental factors during embryonic development. Because the cranial nerves and ocular muscles are developing between the third and eighth weeks of pregnancy, this is most likely when the disturbance happens. It appears that several factors may be involved in Duane syndrome, and a single mechanism is unlikely to be responsible for this condition.

Although Duane syndrome has been well described clinically, the etiology remains unclear. Various theories have been put forward on the basis of data collected from surgical, autopsy, and EMG studies. A high prevalence of ocular and systemic disorders associated with Duane syndrome suggests that a common teratogenic stimulus at 8 weeks of gestation may cause this problem. The most noted and believed theory is based on an absence of cranial nerve VI, an absence of the abducens nucleus in the pons, and a marked abnormality of the lateral rectus muscle.

Most likely, both genetic factors and environmental factors play a role in the development Duane syndrome. In patients with evidence of a genetic cause, both dominant forms and recessive forms of Duane syndrome have been found. The chromosomal location of the proposed gene is currently unknown. Research shows that more than 1 gene may be involved. Evidence suggests that the gene involved in the development of Duane syndrome is located on chromosome 2. Also, deletions of chromosomal material from chromosomes 4 and 8, as well as an extra marker chromosome thought to be derived from chromosome 22, have been linked to Duane syndrome. See also Genetic and environmental factors in the Pathophysiology section.

Structural anomalies

In the early literature, most authors believed that structural anomalies were the cause of the retraction phenomenon. People found posterior insertion of the medial rectus muscle, which acts as a retractor bulbi.

von Noorden found a broad, flat, tendinous band containing a few visible fibers inserted into the sclera at a point 6 mm behind the medial rectus insertion.[16]

Turk believed that fixation of the globe by a nonelastic lateral rectus muscle was the cause of retraction on adduction.[4]

The abnormal vertical eye movement that frequently occurs with adduction has been blamed on oblique overaction. Narrowing of the palpebral fissure usually is explained as passive adjustment of the lid to retraction of the globe, rather than active innervation of the orbicularis muscles.

Innervational anomalies

Evidence accumulated from EMG studies has indicated an innervational mechanism rather than anatomic abnormalities as the cause of this syndrome.

The currently favored theory is that Duane syndrome is a neurogenic disorder involving either a supranuclear lesion or a cranial nerve anomaly in which branches of the oculomotor nerve innervate the lateral rectus.

Hoyt and Nachtigaller have proposed that ocular retraction during adduction, as well as the EMG findings of synergistic innervation of medial and lateral rectus muscle, can be explained on the basis of substitute innervation of the paretic lateral rectus muscle by an extra branch of the oculomotor nerve.[18]

Primary brainstem anomaly

On autopsy, authors at the Wilmer institute found the absence of abducens nuclei and nerves from the brainstem. Matteucci has described absence of abducens nerve and hypoplasia of its nucleus.[19]

Given the clinical evidence, anomalies of the vestibulo-ocular reflex, auditory evoked responses, optokinetic nystagmus, and frequent association of gustatolacrimal reflex (crocodile tears) with Duane syndrome suggests that a primary brainstem abnormality is a likely cause in at least some cases.

Iatrogenic factors

Duane syndrome may occur on an iatrogenic basis unrelated to congenital, mechanical, or innervational anomalies. von Noorden reports a patient who had normal ocular motility and developed retraction syndrome after massive scarring following removal of a dermolipoma from the temporal aspect of the bulbar conjunctiva of the left eye.[16]

At this time, several etiology factors may be involved, and it is doubtful that a single mechanism is responsible for this disturbance.

 

DDx

Diagnostic Considerations

Disorders similar in presentation to Duane syndrome (DS) can be acquired as a result of trauma or following localized infection of the orbit leading to inflammation and consequent mechanical restrictions of eye movement. In such cases, a thorough history will usually help in distinguishing between these conditions. In the clinical setting, the principal difficulties in differential diagnosis arise as a consequence of the very early age at which patients with this condition first present. The clinician must be persistent in examining abduction and adduction, as well as in looking for any associated palpebral fissure changes or head postures, when attempting to determine whether what often presents as a common childhood squint is, in fact, Duane syndrome. Fissure changes and the other associated characteristics of Duane syndrome, such as upshoots or downshoots and globe retraction, are also vital when deciding whether any abduction limitation is the result of Duane syndrome and not a consequence of cranial nerve VI or abducens cranial nerve palsy.

Duane syndrome with radial-ray anomalies (see also Differential diagnosis and other problems to be considered in the Physical section)

Moebius syndrome

Congenital or familiar esotropia

Congenital oculomotor apraxia

Epicanthal folds

Convergence or accommodative excess

Orbital pseudotumor

Grave disease

Ocular anomalies commonly associated with Duane syndrome

Dysplasia of the iris stroma

Papillary anomalies

Cataracts

Heterochromia

Coloboma

Crocodile tears

Microphthalmos

Systemic anomalies

Goldenhar syndrome

Klippel-Feil anomalad

Congenital labyrinthine deafness

Differential Diagnoses

 

Workup

Other Tests

On testing of brainstem auditory evoked responses, findings of Duane syndrome (DS) are occasionally abnormal, suggesting widespread neurologic abnormalities.

EMG findings show absent lateral rectus firing on attempted abduction and firing of both horizontal recti on attempted adduction.

The affected lateral rectus muscle behaves like a muscle double innervated by a weak abducens nerve and a stronger oculomotor nerve branch or like a muscle only innervated by an oculomotor nerve branch. This finding demonstrates that, though a muscle is present, it has a functioning yet an abnormal nerve supply.

Likewise, simultaneous EMG recording of the lateral and medial recti muscles revealed a paradoxical innervation of the lateral rectus muscle to be the pathogenetic principle of all forms of Duane syndrome.

Histologic Findings

Early histopathologic and surgical studies led to the conclusion that Duane syndrome was a local, purely myogenic phenomenon. Therefore, the generally accepted concept was that the cause of abduction deficiency was fibrosis of the lateral rectus muscle and that the limitation of adduction was caused by a false posterior insertion of the medial rectus muscle or by adhesions between the medial rectus muscle and the orbital wall.

N. R. Miller and coauthors from the John Hopkins University performed complete intracranial and orbital pathologic examination of 2 cases of Duane syndrome in which the clinical findings were well documented.[20] The first case was bilateral Duane syndrome type 3. Postmortem examination of the brainstem and the posterior parts of the orbits revealed bilateral absence of the abducens nuclei and the abducens nerves. No large motor neurons were identified at levels the abducens nuclei normally occupy. No intra-axial fibers referable to the sixth cranial nerve could be identified with the brainstem. Both oculomotor nuclei and nerves were normal at the level of the ciliary ganglion, the inferior division of the oculomotor nerve divided into several branches penetrating the inferior medial aspect of the lateral rectus muscle.

The other case showed only 2 thin atrophic fibers of 0.1-mm diameter, both of which had separate exits (1 mm distance between them) from the dura. The further course of these fibers could not be examined.

 

Treatment

Medical Care

Standard therapies

Standard management of Duane syndrome (DS) may involve surgery. The goal of surgery is the elimination or improvement of an unacceptable head turn, the elimination or reduction of significant misalignment of the eyes, the reduction of severe retraction, and the improvement of upshoots and downshoots.

Surgery does not eliminate the fundamental abnormality of innervation and no surgical technique has been completely successful in eliminating the abnormal eye movements. Simple horizontal muscle recession procedures, vertical transposition of the rectus muscle, or combinations of the 2 may be successful in improving or eliminating head turns and misalignment of the eyes.[21] The choice of procedure must be individualized.

Treatment and interventions

Any treatment is aimed at correcting a notable face turn or strabismus. Special seating may be needed in school to accommodate a child's head turn. Special rear-view mirrors help during driving.

A prism can be placed on the patient's glasses to correct for the face turn (though this is not commonly used).

Vision therapy can be used to treat secondary convergence insufficiency.

Surgery

The success rate in eliminating an abnormal head position is 79-100%. Results are stable for at least 8.75 years after surgery. Surgery does not improve motility. Surgery does not improve stereo or fusion. A risk of diplopia may be present with or without surgery.

The goal of surgery is to correct the face turn, decrease upshoots and downshoots, eliminate globe retraction, and align the eyes in primary position.

Surgery can be done any time, but it is usually deferred until the child can walk.

Consider the patient's motor development (eg, ability to walk or catch a ball).

Types of surgery are as follows:

  • Duane syndrome type 1: Recession of the medial rectus (no effect on abduction), posterior fixation suturing on the normal medial rectus (may diminish adduction innervation slightly to the involved eye, decreasing the esodeviation), or resection involving the lateral rectus (but may turn type 1 into a severe type 2).
  • Duane syndrome type 2: Recession of the lateral and medial rectus muscles in the involved eye (may need to recess the contralateral lateral rectus if deviation or retraction is severe), or medial rectus recession on the affected side. [22]
  • Duane syndrome type 3: Recession of the medial and lateral rectus muscles for retraction or an upshoot or downshoot (best for severe cases), Y split of the lateral rectus can reduce retraction upshoot or downshoot, or posterior fixation suturing on the lateral rectus reduces upshoot and downshoot.
  • Duane syndrome type 4: Recession of both lateral rectus muscles (larger amount on the involved side than on the uninvolved side), or surgery designed for the unique patient with rare types.

Surgical Care

Strabismus surgery can be performed if the patient has a clinically significant anomalous head position.

The results of surgical treatment of the retraction syndrome often have been disappointing. For this reason, surgical intervention is not performed when binocular vision is present with the eyes in primary position or if vision can be maintained with a slight head turn. However, the aberrant innervation in Duane syndrome produces different manifestations, any one of which may require surgery. The clinically significant manifestations include a face turn with strabismus in primary position, an upshoot or downshoot during adduction, vertical deviation in primary position, retraction during adduction, and enophthalmos.

Indications

Although none of the findings listed above is an absolute indication for surgery, the need for surgery depends on the severity of the manifestations and the degree to which patients believe that they are disfigured or functionally compromised (as can be the case with a large face turn). The most common indication for surgical treatment is an unacceptable face turn. The face turn is a secondary manifestation of strabismus in primary position and develops to permit fusion. If it is sufficiently large, the face turn may be disfiguring and functionally debilitating.

Patients who have Duane syndrome with exotropia in primary position usually have a face turn away from the affected eye. Most commonly, esodeviation in primary position leads to a face turn toward the side of the affected eye. This face turn is usually most pronounced with distant fixation. The face turn and measured deviation with near fixation may be minimal, but this situation is not a contraindication to surgery because a procedure designed to fully correct the face turn at a distance generally does not produce secondary overcorrection at near fixation.

On occasion, fusion is impossible in a patient with Duane syndrome, usually because bilateral involvement or a vertical deviation prevents fusion with any head posture. In these cases, the strabismus itself rather than the secondary head posture can be the main indication for surgical correction.

When the affected eye is adducted, an upshoot, downshoot, or retraction can be sufficiently disturbing to the patient or the parents of the patient to warrant surgical treatment. The retraction may be accentuated by the face turn that is seen with the most common esotropic form of Duane syndrome; this places the affected eye in an adducted position. In severe cases, clinically significant enophthalmos and pseudoptosis is present even in primary position. A reduction of 50% or more of the width of the palpebral fissure during adduction compared with primary position has been suggested as an indication for surgical treatment of the retraction.

Contraindications

Many patients with Duane syndrome are orthophoric in primary position or have only an insignificant face turn. In these cases, surgery is not indicated unless another manifestation of Duane syndrome, such as an upshoot or a downshoot, is causing some hardship. The fact that a patient seeks evaluation does not necessarily indicate a desire for surgical correction. Often, it is not the manifestations of the condition themselves that have motivated the consultation, but rather, a concern that they indicate some ominous underlying intracranial disease, especially in parents who bring their child with Duane syndrome to be examined.

If discussion with the patient or the patient's parents reveals that fear of life-threatening disease rather than a manifestation of Duane syndrome is their chief concern, then explanation and reassurance may be all that is needed.

Because fusion can usually be achieved by means of a face turn, most children with Duane syndrome have normal binocular function and stereopsis. Therefore, in distinction to congenital esotropia, for which the goal is to restore ocular alignment as early as possible, the goal in Duane syndrome should be to avoid disrupting normal binocular development. Therefore, a young age is a relative contraindication for surgery.

Severe cases may warrant early treatment, but it is usually preferable to delay surgery until patients are aged 4-5 years. At this age, patient cooperation facilitates detailed examination, and their visual system is relatively mature and less susceptible to damage from a temporary disruption of binocularity than before, as can occur postoperatively if an unfavorable response to surgery occurs.

Procedures

Recession of the medial rectus muscle in the involved eye aligns the eye but does not improve abduction beyond the primary position. In rare cases, large weakening procedures performed on the medial rectus lead to consecutive exotropia because of poorly understood mechanisms. Small medial rectus recession in the opposite eye helps the involved eye in primary position by application of the Hering law.

Resection of the lateral rectus muscle is avoided because it increases retraction and does not improve abduction. Recession of the ipsilateral medial rectus muscle is the mainstay of surgical treatment of Duane syndrome. In patients with esotropia in primary position, this procedure improves the face turn and the esotropia by weakening the antagonist of an effectively paretic lateral rectus muscle.

Medial rectus recession alone may improve the enophthalmos and vertical overshoots in adduction, in part by limiting adduction of the eye. However, additional measures are usually needed to adequately manage these problems if they are severe. To effectively reduce or eliminate the face turn, recession must be larger than that typically performed on a medial rectus muscle, often in the range of 8-10 mm, as measured from the original insertion.

Standard recession or a hang-back technique may be used; this can decrease the difficulty of the procedure when a large recession is needed. When clinically significant mechanical restriction due to contracture or fibrosis of the medial rectus muscle is present, a relatively small recession is usually sufficient. A large recession can easily cripple a fibrotic muscle, which often has contractile properties that are almost as severely compromised as its elastic properties.

For adults with mechanical restriction of the medial rectus muscle, techniques for adjustable-suture recession is helpful for finding the best compromise between adequate relief of the face turn and crippled adduction.

Recession of the contralateral medial rectus muscle in addition to the ipsilateral medial rectus muscle may be performed in cases in which the patient has primary position esotropia greater than 20 diopters and marked co-contraction of the lateral rectus muscle, as shown by limited adduction, massive retraction, or reduced adduction saccadic velocities.

Recessing the contralateral medial rectus muscle may allow for decreased recession of the ipsilateral medial rectus muscle. However, millimeter for millimeter, this procedure is less effective than it is in concomitant esotropia because it is an attempt to treat the large secondary deviation. The ipsilateral medial rectus recession still must be sufficient to permit abduction of the ipsilateral eye to at least midline; otherwise, the addition of a contralateral medial rectus recession, regardless of size, cannot correct the face turn. Recession of the contralateral medial rectus muscle may also reduce the long-term risk of contracture of the ipsilateral medial rectus muscle by reducing its tonic innervation (Hering law).

Transposition of the vertical rectus muscles to a position adjacent to the lateral rectus, with or without recession of the ipsilateral medial rectus, has been suggested as a means of correcting the primary position esotropia, of improving abduction, and of enlarging the field of single binocular vision.

This procedure may provide better abduction than that possible with medial rectus recession alone. However, it is more difficult to perform than the other procedure; it may exacerbate retraction, upshoot, or downshoot; it can create new vertical deviations; and, particularly in adults in whom medial rectus recession is performed concurrently, it poses some risk of anterior segment ischemia. This procedure should probably be considered only as primary treatment of patients with no abduction at all, for those with minimal retraction, and for those with no upshoot or downshoot.

Exodeviation in primary position with a face turn away from the side of the affected eye is an uncommon presentation of Duane syndrome. In this case, the face turn is treated with recession of the ipsilateral lateral rectus muscle. In patients who have both primary position exotropia and a marked upshoot or downshoot, a lateral rectus recession is usually combined with an additional measure—either a Y-splitting procedure or a posterior fixation suture—to minimize sideslip of the lateral rectus muscle across the globe.

Recession of the lateral rectus is also effective in reducing the upshoot or downshoot during adduction when it is due to sideslip of a tight lateral rectus, particularly if it is combined with recession of the medial rectus. Recession of the lateral rectus muscle alone improves the retraction with adduction somewhat. However, large recessions (10-12 mm) of both the medial and lateral rectus muscles of the ipsilateral eye are effective, particularly when enophthalmos in primary position is a major complaint. As with medial rectus recessions, recessions of the lateral rectus muscles should be decreased when restriction of the lateral rectus muscle is clinically significant.

Co-contraction of the medial and lateral rectus muscles on attempted adduction can cause a striking upshoot or downshoot of the eye. This effect is attributed to sideslip of a tight lateral rectus over the globe (mechanical factors) in most cases.

The Y-splitting procedure effectively results in a broad lateral rectus insertion that stabilizes its position and prevents it from flipping superiorly or inferiorly over the globe, eliminating or greatly reducing the upshoot or downshoot of the affected eye in attempted adduction. The Y-splitting procedure may be combined with a moderate recession of the lateral rectus muscle, particularly if associated primary position exotropia exists.

Placement of a posterior fixation suture on the lateral rectus muscle can effectively prevent slippage of the muscle belly over the globe. This may be used as an alternative procedure to treat upshoots and downshoots. As with the Y-splitting procedure, posterior fixation suturing can be combined with a lateral rectus recession when appropriate.

Besides the mechanical factors discussed above, innervational factors, presumably aberrant co-contraction of the vertical rectus or inferior oblique muscles, may contribute to an upshoot or a downshoot in some patients with Duane syndrome. When vertical deviation in primary position is clinically significant, surgery on the horizontal rectus muscle alone generally does not correct the problem adequately, and recession of the appropriate vertical rectus muscle is needed. The upshoot in adduction that often is seen in Duane syndrome bears some resemblance to inferior oblique overaction, but inferior oblique weakening procedures usually are ineffectual in correcting the problem.

Expected results

Horizontal muscle recession reportedly eliminates the face turn in 79% of patients and substantially reduces the face turn in most of remaining patients. In a patient with esotropic Duane syndrome, recession of the ipsilateral medial rectus muscle usually provides a modest improvement in abduction if some abduction past the midline was present preoperatively; however, this improvement often comes at the expense of some reduction of adduction. The field of single binocular vision is shifted to include primary position but remains relatively unchanged in size.

On the contrary, if the patient does not have abduction past the midline before surgery, medial rectus recession that is sufficiently large to eliminate the primary position esotropia and face turn substantially limit adduction while providing little or no improvement in abduction.

The size of the field of single binocular vision may be reduced under the circumstances just described, though the addition of a contralateral medial rectus recession, possibly with a Faden procedure, may reduce or eliminate the reduction. Vertical rectus transposition may provide improve abduction and enlarged the field of single binocular vision, particularly in patients with problems with the latter. However, no studies have been conducted to directly compare the efficacy of transposition with that of unilateral or bilateral medial rectus recession.

When they are due to mechanical factors, upshoots and downshoots can usually be satisfactorily reduced or eliminated by performing Y-splitting, posterior fixation, or large recessions of both ipsilateral horizontal rectus muscles. In contrast, when the upshoot or downshoot is due to innervational factors, appropriate recession of a vertical rectus muscle eliminates the vertical deviation in primary position, but some vertical deviation usually remains when the eye is adducted. Large recessions of both horizontal rectus muscles usually provide satisfactory correction of enophthalmos in primary position, but some retraction in adduction remains.

Complications

Undercorrection of the primary position esotropia and face turn probably is the most common adverse outcome after surgical treatment of Duane syndrome, especially when surgeons use amounts of recession typical of their experience in treating concomitant esotropia.

Undercorrection may be obvious in the immediate postoperative period, or the face turn may reappear years after what initially appeared to be a good result. The face turn is presumably due to contracture of the ipsilateral medial rectus muscle.

Undercorrection can be managed by means of vertical rectus transposition or by means of repeat recession of the medial rectus muscle, if the initial recession was relatively small (< 8 mm). Repeat recession of the medial rectus is necessary if passive duction testing still indicates restriction.

With the large recessions necessary to treat Duane syndrome, overcorrection occasionally occurs. Treatment of this secondary exotropia consists of advancement of the recessed medial rectus muscle or recession of the lateral rectus muscle, particularly if passive ductions indicate tightness of the lateral rectus muscles.

New vertical deviations may result from vertical rectus transposition. This condition is treated with (1) dissection (which involves considerable scar tissue) and recession of the appropriate transposed vertical rectus muscle in the ipsilateral eye, particularly if vertical passive ductions are positive, or (2) recession of the appropriate vertical rectus muscle in the contralateral eye.