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Duane retraction syndrome
A rare, ocular congenital cranial dysinnervation disorder characterized by limited horizontal eye movement accompanied by globe retraction and palpebral fissure narrowing on attempted adduction.
ORPHA:233Classification level: Disorder
Duane retraction syndrome (DRS) prevalence is estimated at between 1/1000 and 1/10,000 in the general population, representing approximately 1-5% of all strabismus cases. Females are more frequently affected than males.
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. Development of amblyopia is possible. The majority of DRS cases (70%) are not associated with other anomalies. DRS can be classified based on the extent of abduction and adduction: limited or absent abduction with normal or slightly limited adduction (type I) , normal or mildly restricted abduction with limited or absent adduction (type II), absent or limited abduction and adduction (type III). In all types, there is 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. Globe retraction and fissure narrowing are due to co-contraction of the medial and lateral rectus muscles on attempted adduction, which is itself secondary to aberrant innervation of the lateral rectus by the oculomotor nerve. Identified genetic pathogenic variants include CHN1 or MAFB and rarely, SALL4.
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 due to CHN1 mutations, the optic (CNII), oculomotor (CNIII) and/or trochlear (CNIV) nerves may also be hypoplastic.
Differential diagnosis of isolated DRS includes syndromic forms of DRS such as Duane-radial ray syndrome (Okihiro syndrome), Townes-Brocks syndrome, acro-renal-ocular syndrome, Bosley-Salih-Alorainy and Athabaskan brainstem dysgenesis-related disorders, Wildervanck syndrome, and oculo-auriculo-vertebral spectrum. Syndromic DRS can also arise from chromosomal anomalies and copy number variants, primarily on chromosome 8. Differential diagnosis of DRS also includes Moebius syndrome, congenital fibrosis of extraocular muscles, and isolated horizontal gaze palsy without globe retraction with or without progressive scoliosis (HGPPS).
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. When inherited, isolated DRS most commonly segregates in families as an autosomal dominant trait but autosomal recessive inheritance is also possible. In familial forms, DRS is often bilateral; however, 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. Eye 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 detect and prevent amblyopia. Vision therapy is advised for secondary convergence insufficiency.
Isolated DRS is a benign disorder that, if managed appropriately, results in excellent long-term prognosis for vision. In some cases, amblyopia or loss of binocular single vision might develop.