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Duane retraction syndrome
A congenital form of strabismus characterized by limited horizontal eye movement accompanied by globe retraction and palpebral fissure narrowing on attempted adduction. It is an ocular congenital cranial dysinnervation disorder (CCDD) and can lead to amblyopia.
ORPHA:233Classification level: Disorder
Duane retraction syndrome prevalence is estimated at between 1/1000 and 1/10,000 in the general population, representing approximately 1-5% of all strabismus cases. It most often occurs as an isolated, unilateral finding and females are more frequently affected than males. When inherited, isolated DRS most commonly segregates in families as an autosomal dominant trait.
DRS is a congenital disorder, characterized by non-progressive horizontal ophthalmoplegia without ptosis. Vertical eye movement abnormalities may be observed, including upshoot or downshoot on adduction. Isolated, simplex DRS is usually unilateral and the left eye is more commonly affected. At birth, affected infants have restricted abduction and/or adduction, though it may not be appreciated immediately. Most individuals with DRS have strabismus in primary gaze but can use a compensatory head position to align the eyes, avoiding diplopia. The majority of DRS cases (70%) are not associated with other anomalies. DRS can be classified into three types. Type I is characterized by limited or absent abduction, normal or slightly limited adduction, and globe retraction with palpebral fissure narrowing on attempted adduction, affecting one or both eyes. Type II is characterized by normal or mildly restricted abduction, limited or absent adduction, and globe retraction with narrowing of palpebral fissure on attempted adduction, affecting one or both eyes. Type III is characterized by absent or limited abduction AND adduction and globe retraction with narrowing of palpebral fissure on attempted adduction.
DRS results from abnormal development of the pontine abducens nucleus or nerve, unilaterally or bilaterally, leading to failure of the normal innervation of the lateral rectus muscle on the affected side. This results in limited abduction and horizontal gaze palsy. The diagnosis of DRS also requires globe retraction and fissure narrowing secondary to co-contraction of the medial and lateral rectus muscles on attempted adduction. This aspect of the syndrome is due to secondary innervation of the lateral rectus by an aberrant branch of the oculomotor nerve. Autosomal dominant DRS can result from pathogenic variants in CHN1 or MAFB and rarely, SALL4. Familial forms of DRS linked to these genes often present with both eyes affected.
Diagnosis of DRS is based on clinical features. Magnetic resonance imaging of the brainstem reveals small or absent abducens nerves (CNVI). In individuals with DRS secondary to CHN1 mutations, the optic (CNII), oculomotor (CNIII) and/or trochlear (CNIV) nerves may also be hypoplastic.
Differential diagnosis of isolated DRS includes several multi-system, syndromic conditions in which DRS is one symptom. These include Duane-radial ray syndrome (Okihiro syndrome) resulting from dominant mutations in SALL4 , Townes-Brocks syndrome, acro-renal-ocular syndrome, Bosley-Salih-Alorainy and Athabaskan brainstem dysgenesis-related disorders resulting from recessive mutations in HOXA1 , Wildervanck syndrome, and Goldenhar syndrome. Syndromic DRS can also arise from chromosomal anomalies and copy number variants, primarily on chromosome 8. Isolated horizontal gaze palsy without globe retraction can occur with progressive scoliosis (HGPPS) secondary to recessive mutations in ROBO3. Moebius syndrome is the combination of restricted abduction (without palpebral fissure narrowing) and congenital facial weakness. Other CCDDs with ophthalmoplegia include congenital fibrosis of extraocular muscles (CFEOM).
Prenatal and preimplantation genetic testing for at-risk pregnancies is possible if a pathogenic variant has been identified in a family.
Most cases are sporadic, but up to 10% of patients have affected relatives. Inheritance can be dominant or recessive. Incomplete penetrance and variable expressivity can complicate assessments.
Management and treatment
Management of DRS is mainly supportive and involves wearing spectacles or contact lenses to correct refractive errors; occlusion or penalization of the better-seeing eye for treatment of amblyopia or prisms to correct for abnormal head posture. Muscle surgery may be indicated to correct abnormal head position, to align the eyes in primary gaze, or to correct for upshoot or downshoot on adduction. However, surgery does not restore full normal eye movements. Surveillance is necessary to prevent or detect amblyopia. Vision therapy is advised for secondary convergence insufficiency.
Isolated DRS is a benign disorder which, if managed appropriately, results in excellent long-term prognosis for vision. In some cases, amblyopia or loss of binocular single vision might develop.