Clinical Guidance

CHN1. Individuals with pathogenic variants in CHN1 are more likely to have bilateral involvement, vertical movement abnormalities beyond the upshoot and downshoot often seen in Duane syndrome, and a positive family history when compared to individuals with Duane syndrome who do not have a CHN1 pathogenic variant [, , , , ]. MAFB. Individuals with pathogenic variants in MAFB are more likely to have bilateral Duane syndrome and may have mild-to-severe sensorineural hearing loss in addition to the Duane syndrome. Hearing loss was documented in one of four reported pedigrees of otherwise isolated Duane syndrome, and confirmed in three of four individuals in that family . SALL4.

Source: GeneReviews — "Duane Syndrome"

Penetrance

Families with Duane syndrome in whom a CHN1 pathogenic variant has been identified may have reduced penetrance . There has been no evidence of reduced penetrance in the limited number of families with isolated Duane syndrome identified with MAFB or SALL4 pathogenic variants

Source: GeneReviews — "Duane Syndrome"

Diagnostic Criteria

Duane syndrome is a strabismus condition clinically characterized by congenital non-progressive limited horizontal eye movement accompanied by globe retraction which results in narrowing of the palpebral fissure. The diagnosis of Duane syndrome is based on clinical findings and classified into three types . Most affected individuals with Duane syndrome have isolated Duane syndrome (i.e., they do not have other detected congenital anomalies). Other individuals fall into well-defined syndromic diagnoses (see and ). However, many individuals with Duane syndrome have non-ocular findings that are not classified as a particular syndrome; they are included in this review for completeness. The vast majority of individuals with isolated Duane syndrome represent simplex cases (i.e., a single occurrence in a family). A positive family history showing autosomal dominant inheritance is apparent for approximately 10% of affected individuals . Suggestive Findings Duane syndrome, a congenital, non-progressive eye movement disorder, should be suspected in individuals who present with the following features: • Congenital limited horizontal eye movement with impairment of abduction and/or adduction • Globe retraction (co-contraction) accompanied by narrowing of the palpebral fissure (i.e., reduced distance between the upper and lower eyelids) on adduction. Note: Adduction is movement of the globe toward the midline (the nose); abduction is movement of the globe toward the ear, away ("abducted") from the midline. Establishing the Diagnosis Clinical findings. The diagnosis of Duane syndrome is established in a proband typically by an ophthalmologist by detection of the specific clinical findings of limited abduction and/or adduction in association with globe retraction on adduction. Individuals can usually be categorized within the three types detailed below, though there may be some overlap among these categories. Table 1. Clinical Findings: Comparison of Duane Syndrome Types I-III

Source: GeneReviews — "Duane Syndrome"

Differential Diagnosis

Duane syndrome with associated congenital anomalies. Approximately 30% of individuals with Duane syndrome have other congenital anomalies, particularly of the ear, kidney, heart, upper limbs, and skeleton. These associated anomalies are typically reported in simplex cases, but also occur together with Duane syndrome as familial malformation or genetic syndromes. Table 3. Disorders to Consider in the Differential Diagnosis of Duane Syndrome with Associated Congenital Anomalies

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with Duane syndrome, the following evaluations are recommended if they have not already been completed:

• Family history

• Ophthalmologic examination

• Determination of deviation in primary gaze, anomalous head position, and horizontal and vertical gaze restrictions

• Evaluation for aberrant movements. Globe retraction with narrowing of the palpebral fissure in adduction is the sine qua non of Duane syndrome. Infraduction of the affected eye in attempted abduction is a common finding. Other features sometimes observed include up- and downshoot on adduction and Marcus Gunn jaw winking.

• Full ophthalmologic exam to assess for refractive errors, amblyopia, or amblyopia risk factors.

• Optional forced duction testing and/or force generation testing in cooperative individuals

• Photographic documentation to identify changes in the condition and for future review

• If surgery is planned, consideration of brain and orbital MRI to determine brain stem and orbital anatomy (muscles and nerves)

• General physical examination to look for systemic anomalies that can be found in individuals with Duane syndrome

• Hearing evaluation

• Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

Nonsurgical treatment of ophthalmologic findings

Source: GeneReviews — "Duane Syndrome"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Duane Syndrome"

Surveillance Guidelines

Surveillance is important for prevention of amblyopia, and to treat amblyopia if it occurs.

• Routine ophthalmologic visits every three to six months during the first years of life

• Annual or biannual examinations in affected individuals once the presence of binocular vision and reduced risk for amblyopia is confirmed, and in all individuals older than age seven to 12

• No surveillance in adulthood beyond public health guidelines

Source: GeneReviews — "Duane Syndrome"