Duane Syndrome

Excerpt

Clinical characteristics: 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 lateral movement anomaly results from failure of the abducens nucleus and nerve (cranial nerve VI) to fully innervate the lateral rectus muscle; globe retraction occurs as a result of abnormal innervation of the lateral rectus muscle by the oculomotor nerve (cranial nerve III). At birth, affected infants have restricted ability to move the affected eye(s) outward (abduction) and/or inward (adduction), though the limitations may not be recognized in early infancy. In addition, the globe retracts into the orbit with attempted adduction, accompanied by narrowing of the palpebral fissure. Many individuals with Duane syndrome have strabismus in primary gaze but can use a compensatory head turn to align the eyes, and thus can preserve binocular vision and avoid diplopia. Individuals with Duane syndrome who lack binocular vision are at risk for amblyopia. The majority of affected individuals with Duane syndrome have isolated Duane syndrome (i.e., they do not have other detected congenital anomalies). Other individuals with Duane syndrome fall into well-defined syndromic diagnoses. However, many individuals with Duane syndrome have non-ocular findings that do not fit a known syndrome; these individuals are included as part of the discussion of nonsyndromic Duane syndrome.

Diagnosis/testing: The diagnosis of Duane syndrome is usually made by an ophthalmologist based on clinical findings. More than 98% of individuals with isolated Duane syndrome and no family history lack an identified genetic etiology. Molecular genetic testing for a pathogenic variant in CHN1, MAFB, or SALL4 is most appropriate for those with a positive family history of isolated Duane syndrome (although de novo pathogenic variants in these genes have been detected in some simplex cases) and for those with clinical ocular findings designated as type I or type III Duane syndrome.

Management: Treatment of manifestations: Spectacles or contact lenses for refractive error; occlusion or penalization of the better-seeing eye for treatment of amblyopia; prism glasses (usually in older individuals with mild involvement) to improve the compensatory head position; extraocular muscle surgery to address alignment in primary gaze, compensatory head posture, and upshoot or downshoot.

Prevention of secondary complications: Amblyopia therapy to prevent vision loss in the less preferred eye; extraocular muscle surgery to prevent loss of binocular vision in individuals who abandon the compensatory head posture and allow strabismus to become manifest, and to prevent neck muscle problems in those with large compensatory head postures.

Surveillance: Ophthalmologic visits every three to six months during the first years of life to prevent, detect, and treat amblyopia; annual or biannual examinations 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.

Evaluation of relatives at risk: Eye examination within the first year of life so that early diagnosis and treatment can prevent secondary complications.

Genetic counseling: The majority of individuals with isolated Duane syndrome represent simplex cases (i.e., a single occurrence in a family), with a positive family history apparent for only approximately 10% of affected individuals. Duane syndrome resulting from a CHN1, MAFB, or SALL4 pathogenic variant is inherited in an autosomal dominant manner. Most individuals with isolated CHN1-, MAFB-, or SALL4-related Duane syndrome have the disorder as the result of a pathogenic variant inherited from an affected parent. Each child of an individual with Duane syndrome resulting from an identified pathogenic variant has a 50% chance of inheriting the variant. Prenatal and preimplantation genetic testing are possible once the causative pathogenic variant has been identified in an affected family member.