Duane retraction syndrome is a congenital eye movement disorder characterized by a failure of cranial nerve VI (the abducens nerve) to develop normally, resulting in restriction or absence of abduction, adduction, or both, and narrowing of the palpebral ... Duane retraction syndrome is a congenital eye movement disorder characterized by a failure of cranial nerve VI (the abducens nerve) to develop normally, resulting in restriction or absence of abduction, adduction, or both, and narrowing of the palpebral fissure and retraction of the globe on attempted adduction. Undiagnosed in children, it can lead to amblyopia, a permanent uncorrectable loss of vision (Appukuttan et al., 1999). - Genetic Heterogeneity of Duane Retraction Syndrome Duane retraction syndrome-1 (DURS1) maps to chromosome 8q13. Duane retraction syndrome-2 (DURS2; 604356) is caused by mutation in the CHN1 gene (118423) on chromosome 2q31.
This unusual congenital form of strabismus was first described by Duane (1905), who collected reports of 54 cases. The condition is bilateral in 20% of cases.
As discussed by Al-Baradie et al. (2002), Duane syndrome type ... This unusual congenital form of strabismus was first described by Duane (1905), who collected reports of 54 cases. The condition is bilateral in 20% of cases. As discussed by Al-Baradie et al. (2002), Duane syndrome type 1 refers to marked or complete limitation of abduction with minimal or no limitation of adduction. Duane syndrome type 2 refers to marked or complete limitation of adduction with minimal or no limitation of abduction. Duane syndrome type 3 refers to marked or complete limitation of both abduction and adduction. The presence of more than 1 Duane syndrome type within a single pedigree was described by Chung et al. (2000), Evans et al. (2000), and Al-Baradie et al. (2002); see, e.g., 607343.0004. Kim and Hwang (2005) analyzed whether the presence of the abducens nerve might depend upon the type of DRS. The abducens nerve on the affected side could not be observed using MRI in 18 of 18 eyes (16 patients) with type 1 DRS or in 3 of 5 eyes with type 3 DRS. Conversely, the abducens nerve was observed in 2 of 2 eyes with type 2 DRS and 2 of 5 eyes with type 3 DRS. The abducens nerve was observed in 60 of 60 eyes screened as controls. Thus, in terms of the presence or absence of the abducens nerve, type 1 and type 2 DRS were homogeneous and type 3 DRS was heterogeneous. In the study of 25 cases of sporadic Duane retraction syndrome by Wabbels et al. (2004), there was the usual excess of females with M/F ratio of 9/16 (64% females). There was bilateral involvement in only 12% of cases; the left eye was involved in 72%. - Clinical Variability Chung et al. (2000) described the clinical diversity of hereditary Duane retraction syndrome in the 25 affected members of a 118-member, 3-generation family from Oaxaca, Mexico. Twenty-four affected individuals had bilateral DRS with a broad spectrum of severity. Strabismus occurred in 76% and amblyopia in 48%. Both strabismus and amblyopia were much more common in bilateral DRS than in unilateral DRS. Associated findings included fourth cranial nerve palsy, partial third cranial nerve palsy, nystagmus, seizures, and deafness. Fourth cranial nerve palsy and manifest strabismus tended to cluster within single family units. Chung et al. (2000) postulated that the responsible gene(s) may affect the development of many cranial nerves. They suggested that genetic compounding may play a role in the phenotypic segregation seen within this large family. - Association with other Anomalies Duane anomaly with associated deformity of the upper extremity was reported by Gifford (1926), Crisp (1918) and Mennerich (1923). Ferrell et al. (1966) described association of Duane anomaly with a heart-hand syndrome (probably Holt-Oram syndrome; see 142900) in a dominant pattern of inheritance. Hayes et al. (1985) gave the designation Okihiro syndrome (607323) to the combination of Duane anomaly, radial ray abnormalities, and deafness. This syndrome is referred to here as the Duane-radial ray syndrome (DRRS) for mnemonic reasons. Wildervanck syndrome (314600) 'consists of congenital, perceptive deafness, Klippel-Feil anomaly (fused cervical vertebrae), and abducens palsy with retractio bulbi (Duane syndrome).' Vincent et al. (2005) reported an 18-month-old girl with sporadic blepharophimosis, ptosis, and epicanthus inversus (110100) associated with bilateral type 1 Duane syndrome.
In 25 cases of sporadic Duane retraction syndrome, Wabbels et al. (2004) found no mutations in the exons or neighboring intronic regions of the SALL4 gene (607343). The results suggested that SALL4 mutation analysis is not recommended in ... In 25 cases of sporadic Duane retraction syndrome, Wabbels et al. (2004) found no mutations in the exons or neighboring intronic regions of the SALL4 gene (607343). The results suggested that SALL4 mutation analysis is not recommended in nonfamilial Duane retraction syndrome, but careful clinical evaluation of the hands, the ears, the heart, and the kidney is required to exclude Okihiro syndrome (607323), which occurs in sporadic cases, and which in familial cases, like other autosomal dominant disorders, shows marked intra- and interfamilial variability. Because of the identification of a patient with apparently isolated Duane anomaly, who was found additionally to have asymptomatic left carotid hypoplasia (see 142955.0001), Tischfield et al. (2006) analyzed the HOXA1 gene in 101 probands with isolated Duane anomaly (DA) and 30 with DA and other symptoms. More probands had type 1 than type 3, and there were only a few cases of type 2. None in this group harbored a mutation in SALL4 or ROBO3 (608630), and none were members of a pedigree whose phenotype maps to the DURS2 locus. No mutation was detected in any proband; the authors concluded that HOXA1 mutations are a rare cause of isolated Duane anomaly, and recommended screening for clinically silent vascular anomalies in these patients.
Appukuttan et al. (1999) cited a prevalence of approximately 0.1% in the general population and indicated that Duane retraction syndrome accounts for 5% of all strabismus cases.
Duane syndrome, a congenital, non-progressive eye movement disorder, is characterized by the following:...
DiagnosisClinical DiagnosisDuane syndrome, a congenital, non-progressive eye movement disorder, is characterized by the following:Congenital limitation of abduction and/or adduction Globe retraction (co-contraction) on adduction Palpebral fissure (i.e., the separation between the upper and lower eyelids) narrowing on adduction. Note: Adduction is movement of the globe toward the midline (the nose); abduction is movement of the globe away from the midline (toward the ear).Isolated Duane syndrome. Most individuals with Duane syndrome have isolated Duane syndrome, i.e., they do not have other detected congenital anomalies. The vast majority of individuals with isolated Duane syndrome are simplex cases (i.e., single occurrence in a family). This GeneReview focuses on isolated Duane syndrome. (See Differential Diagnosis for a discussion of Duane syndrome with associated congenital anomalies.) Duane syndrome can be clinically subdivided into three types:Type 1 (~75%-80% of all Duane syndrome) is characterized by the following: Absent to markedly restricted abduction Normal to mildly restricted adduction Retraction of the globe and narrowing of the palpebral fissure on adduction Upshoot and downshoot of affected globe on attempted adduction Esotropia in primary gaze (variably present) Head turn toward involved side (variably present) Unilateral or bilateral involvement Type 2 (~5%-10% of all Duane syndrome) is characterized by the following: Absent to markedly restricted adduction Normal to mildly restricted abduction Retraction of the globe and narrowing of the palpebral fissure (the separation between the upper and lower eyelids) on adduction Upshoot and downshoot of affected globe on attempted adduction (variably present) Exotropia in primary gaze (variably present) Head turn toward uninvolved side (variably present) Unilateral or bilateral involvement Type 3 (~10%-20% of all Duane syndrome) is characterized by the following: Absent to markedly restricted abduction Absent to markedly restricted adduction Retraction of the globe and narrowing of the palpebral fissure on attempted adduction Upshoot and downshoot of affected globe on attempted adduction (more common than in types 1 or 2) Esotropia or exotropia in primary gaze (variably present) Head turn toward involved side (variably present) Unilateral or bilateral involvement Molecular Genetic TestingGene. CHN1 is by definition the only gene in which mutations are known to cause CHN1-related familial isolated Duane syndrome. Clinical testingTable 1. Summary of Molecular Genetic Testing Used in Duane Syndrome View in own windowGene Symbol Test MethodMutations DetectedMutation Detection Frequency by Test Method 1Test AvailabilityCHN1Sequence analysisSequence variants 2, 3UnknownClinical1. The ability of the test method used to detect a mutation that is present in the indicated gene2. Examples of mutations detected by sequence analysis may include small intragenic deletions/insertions and missense, nonsense, and splice site mutations; typically, exonic or whole-gene deletions/duplications are not detected.3. Miyake et al [2008], Murillo-Correa et al [2009], Miyake et al [2010], Volk et al [2010], Chan et al [2011], Miyake et al [2011]Interpretation of test results. For issues to consider in interpretation of sequence analysis results, click here.Information on specific allelic variants may be available in Molecular Genetics (see Table A. Genes and Databases and/or Pathologic allelic variants).Testing Strategy To confirm/establish the diagnosis in a probandThe diagnosis of Duane syndrome is established by clinical findings.Molecular genetic testing of CHN1 is recommended in familial cases only.Prenatal diagnosis and preimplantation genetic diagnosis (PGD) for at-risk pregnancies require prior identification of the disease-causing mutation in the family.Genetically Related (Allelic) Disorders Gain of function CHN1 mutations have also been identified in individuals with vertical strabismus and supraduction deficits in the absence of Duane retraction syndrome.
Duane syndrome is a strabismus syndrome characterized by congenital non-progressive horizontal ophthalmoplegia (inability to move the eyes) without ptosis (droopy eyelids) primarily affecting the abducens nucleus and nerve and its innervated extraocular muscle, the lateral rectus muscle. At birth, affected individuals have restricted ability to move the affected eye(s) outward (abduction) and/or inward (adduction). In addition, the globe retracts into the orbit with attempted adduction, accompanied by narrowing of the palpebral fissure. The left side is more commonly affected in most studies....
Natural HistoryDuane syndrome is a strabismus syndrome characterized by congenital non-progressive horizontal ophthalmoplegia (inability to move the eyes) without ptosis (droopy eyelids) primarily affecting the abducens nucleus and nerve and its innervated extraocular muscle, the lateral rectus muscle. At birth, affected individuals have restricted ability to move the affected eye(s) outward (abduction) and/or inward (adduction). In addition, the globe retracts into the orbit with attempted adduction, accompanied by narrowing of the palpebral fissure. The left side is more commonly affected in most studies.The female-to-male ratio for simplex cases is 3:2.Restriction in vertical movement of the eyes may also be found in association with mutations in CHN1.Strabismus, the deviation of the position of one eye relative to the other, results in misalignment of the line of sight of the two eyes. Many individuals with Duane syndrome have strabismus in primary gaze; esotropia is more common in Duane syndrome type 1 and exotropia in Duane syndrome type 2. The impaired movement of one eye with respect to the other allows individuals with strabismus in primary gaze to utilize a compensatory head turn in order to align the eyes, thus avoiding diplopia and preserving single binocular vision. Amblyopia occurs in approximately 10% of individuals with Duane syndrome; these persons are typically a subset of those with Duane syndrome who lack binocular vision. The amblyopia in Duane syndrome responds to standard therapy if detected early; if not treated promptly, the vision loss from amblyopia is irreversible. Visual acuity is good except in those individuals with amblyopia. Marcus Gunn jaw-winking phenomenon. Individuals with Duane syndrome and Marcus Gunn jaw-winking phenomenon have been reported, lending support to the idea that the two syndromes are primarily neurogenic in origin [Isenberg & Blechman 1983, Oltmanns & Khuddus 2010]. Pathophysiology. It is generally believed that Duane syndrome results from maldevelopment of motor neurons in the abducens nucleus and aberrant innervation of the lateral rectus muscle. Early studies of Duane syndrome reported fibrosis of the lateral rectus or medial rectus muscles, and suggested a primary myopathic etiology for this disorder. Subsequently, several postmortem examinations of individuals with simplex Duane syndrome revealed absence of the abducens motor neurons and ipsilateral cranial nerve VI, and partial innervation of the lateral rectus muscle(s) by branches from the oculomotor nerve. Electromyography revealed simultaneous activation of the medial and lateral rectus muscles, supporting co-contraction of these two horizontal muscles as the cause of the globe retraction. Neuroimaging. Magnetic resonance imaging (MRI) in simplex cases has verified the absence of cranial nerve VI.Orbital and brain stem MRI of affected members of two pedigrees with a CHN1 mutation did not visualize the abducens nerve in most affected individuals and revealed structurally abnormal lateral rectus muscles. The oculomotor and optic nerves were also small [Demer et al 2007]. Decreased superior oblique muscle volume has also been observed, supporting trochlear nerve hypoplasia [Miyake et al 2011]. This leads to the suggestion that Duane syndrome resulting from mutations in CHN1 represents a congenital cranial dysinnervation disorder that results from errors in abducens, trochlear, and oculomotor axon pathfinding.
The incidence of bilateral involvement and vertical movement abnormalities in CHN1 mutation-positive individuals with Duane syndrome is higher than that found in CHN1 mutation-negative individuals with Duane syndrome who are simplex cases (i.e., a single occurrence in a family) [Chung et al 2000, Demer et al 2007, Engle et al 2007, Miyake et al 2008]. ...
Genotype-Phenotype CorrelationsThe incidence of bilateral involvement and vertical movement abnormalities in CHN1 mutation-positive individuals with Duane syndrome is higher than that found in CHN1 mutation-negative individuals with Duane syndrome who are simplex cases (i.e., a single occurrence in a family) [Chung et al 2000, Demer et al 2007, Engle et al 2007, Miyake et al 2008].
Differential DiagnosisTable 2. Duane Retraction Syndrome: OMIM Phenotypic SeriesView in own windowPhenotypePhenotype MIM NumberGene/LocusGene/Locus MIM NumberDuane retraction syndrome 1126800 DURS1, DUS 126800 Duane retraction syndrome 2 604356 CHN1, CHN, ARHGAP2, RHOGAP2, DURS2 118423 Data from Online Mendelian Inheritance in ManDuane 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. SALL4-related disorders. The SALL4-related syndromes include Okihiro syndrome, Duane-radial ray syndrome, acro-renal-ocular syndrome, and IVIC syndrome. These overlapping syndromes are characterized by unilateral or bilateral Duane syndrome and radial ray malformations that can include thenar hypoplasia and/or hypoplasia or aplasia of the thumbs; hypoplasia or aplasia of the radii; shortening and radial deviation of the forearms; triphalangeal thumbs; and duplication of the thumb (preaxial polydactyly). Deafness, renal anomalies, and imperforate anus can be co-inherited. Inheritance is autosomal dominant. Heterozygous SALL4 mutations are associated with most familial cases of these syndromes [Al-Baradie et al 2002, Kohlhase et al 2002, Kohlhase et al 2003, Kohlhase et al 2005, Paradisi & Arias 2007]. Individuals with simplex isolated Duane syndrome have not been found to harbor mutations in SALL4 [Wabbels et al 2004]. However, some members of families segregating a SALL4-related disorder have been found to harbor a SALL4 mutation and to manifest isolated Duane syndrome (without hand or other anomalies) [Al-Baradie et al 2002]. SALL1-related disorders. Townes-Brocks syndrome (TBS) has been found to result from mutations in SALL1 [Kohlhase et al 1998]. This rare disorder is characterized by renal, anal, limb, and ear anomalies and is an autosomal dominantly inherited malformation syndrome. More recently SALL1 mutations have been reported in three individuals with TBS and Duane syndrome [Botzenhart et al 2007, Barry & Reddy 2008, van den Akker et al 2009]. Additional ophthalmic findings in these individuals included coloboma, ptosis, epibulbar dermoid, and crocodile tears. There is overlap between TBS and Okihiro syndrome.HOXA1-related syndromes. The HOXA1-related syndromes include the overlapping Bosley-Salih-Alorainy syndrome (BSAS, OMIM 601536) [Tischfield et al 2005] and Athabaskan brain stem dysgenesis syndrome (ABDS) [Holve et al 2003]. They are characterized by Duane syndrome type 3 or horizontal gaze palsy and, in most individuals, bilateral sensorineural hearing loss caused by an absent cochlea and rudimentary inner-ear development. Subsets of individuals manifest intellectual disability, autism, moderate-to-severe central hypoventilation, facial weakness, swallowing difficulties, vocal cord paresis, conotruncal heart defects, and skull and craniofacial abnormalities. These disorders result from truncating mutations in HOXA1 [Tischfield et al 2005]. Inheritance is autosomal recessive. Individuals with simplex isolated Duane syndrome have not been found to harbor mutations in HOXA1 [Tischfield et al 2006].Wildervanck syndrome (cervicooculoacoustic syndrome, OMIM 314600) is characterized by Duane syndrome, deafness, and Klippel-Feil anomaly (fused cervical vertebrae). The perceptive deafness results from a bony malformation of the inner ear. Most Wildervanck syndrome is sporadic and limited to females. Goldenhar syndrome (hemifacial microsomia, oculoauriculovertebral spectrum, OMIM 164210) is characterized by craniofacial, ocular, cardiac, vertebral, and central nervous system defects, consistent with maldevelopment of the first and second branchial arches. Duane syndrome can be associated with this disorder [Tillman et al 2002, Caca et al 2006]. The majority of cases are sporadic, but there are a few reports of both autosomal dominant and recessive inheritance (see Craniofacial Microsomia Overview).Chromosome disordersChromosome 8. Several individuals with Duane syndrome have been reported to have chromosome 8 anomalies: anomalies of the 8q13 DURS1 locus (OMIM 126800); mosaic trisomy 8 [2 separate reports]; deletion 8q13-q21.2; a de novo reciprocal balanced translocation consisting of t(6:8)(q26;q13) disrupting the gene for carboxypeptidase (CPAH); and a microduplication of 8q12. Two reports suggest that abnormal dosage of CHD7 may be causative of the resultant phenotype on 8q12. Individuals described in these case reports manifest Duane syndrome with various associated congenital abnormalities including other cranial nerve deficits, facial dysmorphisms, intellectual disabilities, and cardiac defects.Other chromosome aberrations associated with Duane syndrome have been reported to involve 2q13, 4q27-31, 6p25, 10q24.2q26.3, 20q13.12 and 22pter-q11. Duane syndrome has been described in one individual with 48,XXYY syndrome and another with atypical Silver-Russell syndrome, Duane syndrome and maternal uniparental disomy of chromosome 7.Individuals with Duane syndrome and associated congenital defects should be evaluated further for possible underlying chromosomal rearrangements.Ocular congenital cranial dysinnervation disorders. The term congenital cranial dysinnervation disorders (CCDDs) refers to disorders of innervation of cranial musculature [Gutowski et al 2003]. The ocular CCDDs are also included in the category of complex or incomitant strabismus, in which the degree of misalignment of the eyes varies with the direction of gaze. Duane syndrome is the most common of the ocular CCDDs. Other ocular CCDDs include the following:Congenital fibrosis of the extraocular muscles (CFEOM) (OMIM 135700, 602078, 600638, 609428, 609384) refers to at least seven genetically defined syndromes: CFEOM1A, CFEOM1B, CFEOM2, CFEOM3A, CFEOM3B, CFEOM3C, and Tukel syndrome. CFEOM is characterized by congenital non-progressive ophthalmoplegia (inability to move the eyes) that is restrictive and includes some limitation of vertical gaze. It often but does not have to include ptosis (droopy eyelids). It typically results from aberrant development of all or part of the oculomotor nucleus and nerve (cranial nerve III) and its innervated muscles (superior, medial, and inferior recti, inferior oblique, and levator palpebrae superioris) and/or the trochlear nucleus and nerve (cranial nerve IV) and its innervated muscle (the superior oblique). In general, affected individuals have severe limitation of vertical gaze and variable limitation of horizontal gaze. Individuals with CFEOM frequently compensate for the ophthalmoplegia by maintaining abnormal head positions at rest and by moving their heads rather than their eyes to track objects. Individuals with CFEOM3A may also have intellectual disability, social disability, facial weakness, and/or a progressive axonal peripheral neuropathy (a form of Charcot-Marie-Tooth disease). Individuals with CFEOM3C also have intellectual disability and facial dysmorphism reminiscent of Albright hereditary osteodystrophy-like syndrome. Individuals with Tukel syndrome also have postaxial oligodactyly or oligosyndactyly of the hands. Moebius syndrome (MBS) (OMIM 157900) is characterized by sixth and seventh nerve palsies, resulting in abduction defect and facial weakness. The vast majority of individuals with Moebius syndrome are simplex cases (i.e., single occurrence in a family) and many are associated with additional developmental defects of lower cranial nerves and distal extremities. Hereditary congenital facial paresis (HCFP) (OMIM 601471) is characterized by the isolated dysfunction of cranial nerve VII. It may be confused with Moebius syndrome if it is coincidentally accompanied by strabismus. Horizontal gaze palsy with progressive scoliosis (HGPPS) (OMIM 607313) is characterized by congenital horizontal gaze palsy (no horizontal eye movements) accompanied by progressive scoliosis. HGPPS is inherited in an autosomal recessive manner and is caused by mutations in ROBO3 [Jen et al 2004]. Compound heterozygous ROBO3 mutations have also been identified in children of non-consanguineous parents [Chan et al 2006]. Neuroimaging and neurophysiology studies of individuals with HGPPS found that the axons that make up the major motor and sensory pathways for communication between the brain and the spinal cord fail to cross the midline in the hindbrain [Jen et al 2004, Bosley et al 2005]. Complex and common forms of strabismus that could be confused with Duane syndrome: Common strabismus. In common or comitant strabismus, the misalignment of the eyes is equal regardless of the direction of gaze. Common strabismus includes esotropia, exotropia, dissociated vertical deviation, microstrabismus, and monofixation syndrome. Sixth nerve palsy is characterized by impaired abduction of the affected eye in the absence of globe retraction and narrowing of the palpebral fissure. Sixth nerve palsy may be accompanied by esotropia. Sixth nerve palsies are typically acquired; however, congenital and/or inherited cases are rare but have been reported. Crossed fixation. The signs of Duane syndrome may be difficult to detect in an infant with large-angle esotropia. In such infants, the right eye is used for left gaze and the left eye is used for right gaze. As a result, the child may appear to have an abduction limitation when in fact abduction is found to be full when tested monocularly. Congenital ocular motor apraxia is a rare disorder of horizontal gaze in which affected individuals are unable to generate horizontal saccades. Horizontal tracking requires head movement, but the head must be thrust past the object of regard in order to overcome the intact doll's head response. Vertical saccades are preserved. Brown syndrome ('superior oblique tendon sheath syndrome') is characterized by the inability to elevate the adducted eye actively or passively. Forced duction testing is positive for tightness of the superior oblique muscle. The downshoot seen in Duane syndrome can mimic Brown syndrome. Most congenital Brown syndrome is simplex (i.e., single occurrence in a family) and believed to result from anomalies of the tendon or the trochlear apparatus. Rare familial cases have been reported [Iannaccone et al 2002]. Congenital esotropia and exotropia refer to eye conditions in which the eye(s) are either crossed or deviating outwards. There is evidence of both genetic and environmental components to these disorders. Note to clinicians: For a patient-specific ‘simultaneous consult’ related to this disorder, go to , an interactive diagnostic decision support software tool that provides differential diagnoses based on patient findings (registration or institutional access required).
To establish the extent of disease in an individual diagnosed with Duane syndrome, the following evaluations are recommended:...
ManagementEvaluations Following Initial DiagnosisTo establish the extent of disease in an individual diagnosed with Duane syndrome, the following evaluations are recommended:Family history Ophthalmologic examination Determination of primary gaze position, head position with eyes in primary 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. Other features sometimes observed include up- and downshoot on attempted adduction and Marcus Gunn jaw wink. Optional forced duction testing and/or force generation testing in cooperative individualsPhotographic documentation to identify changes in the condition and for future review If surgery is planned: Consider brain and orbital MRI to determine brain stem and orbital anatomy (muscles and nerves) General physical examination. Because of association with systemic anomalies, affected children should have a complete physical examination. If surgery is performed, forced duction testing to confirm tightness of the horizontal rectus muscles The following may be considered:Hearing evaluation Medical genetics consultation if there is a family history of Duane syndrome, dysmorphic features and/or congenital anomalies in the proband, or if a mutation is found in CHN1 Treatment of ManifestationsNonsurgical treatment of ophthalmologic findings Refractive errors may be managed with spectacles or contact lenses. Specialist examination is required to detect refractive errors early in life, when affected individuals may be asymptomatic, to prevent amblyopia and avoid compounding the motility problem with a focusing problem. Amblyopia can be treated effectively with occlusion or penalization of the better-seeing eye. Early detection (in the first years of life) maximizes the likelihood of a good response to treatment. Prism glasses may improve the compensatory head position in mild cases. They are more likely to be tolerated by older persons. Correction of hypermetropic refractive error in children may reduce the angle of strabismus and thus decrease the angle of head turn. Surgical treatment of ophthalmologic findings (extraocular muscle surgery) To correct or improve compensatory head posture To improve alignment in primary gaze position To improve upshoot or downshoot Note: Surgery does not generally improve abduction of the affected eye, though transposition procedures may provide partial improvement in some cases. Principles of surgical approach Type 1 and type 3. If head turn is present, consider recession of the medial rectus muscle or horizontal transposition of the vertical rectus muscles. Vertical rectus muscle transposition may be augmented, either with posterior augmentation sutures on the transposed muscles, or with botulinum toxin injections into the medial rectus muscle. Both the superior and inferior rectus muscles may be transposed, or alternatively the superior rectus muscle alone may be transposed in combination with a medial rectus muscle recession. If up and/or downshoot occurs in adduction, or if globe retraction is severe and creates a deformity, consider recession of both the medial and lateral rectus muscles. Y-splitting of the lateral rectus muscle may decrease the amount of recession required. Type 2. If head turn is present, consider recession of the ipsilateral lateral rectus muscle if the affected individual fixates with the uninvolved eye, and the contralateral lateral rectus if the affected individual fixates with the involved eye. If upshoot or downshoot occurs in adduction, consider recession of the lateral rectus muscle, possibly with Y-splitting. Prevention of Secondary ComplicationsThe following are appropriate:Amblyopia therapy to prevent vision loss in the less preferred eye Surgery to prevent loss of binocular vision in individuals who abandon the compensatory head posture and allow strabismus to become manifest SurveillanceSurveillance 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 older than age seven to 12 years who have good binocular vision and thus are no longer at risk for amblyopia Evaluation of Relatives at RiskDuane syndrome can often be diagnosed by clinical findings within the first year of life; early diagnosis can result in early treatment and thus, prevention of secondary complications. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.Therapies Under InvestigationSearch ClinicalTrials.gov 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.
Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED....
Molecular GeneticsInformation in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.Table A. Duane Syndrome: Genes and DatabasesView in own windowLocus NameGene SymbolChromosomal LocusProtein NameLocus SpecificHGMDDURS1Unknown8q13Unknown DURS2CHN12q31.1N-chimaerinCHN1 homepage - Mendelian genesCHN1Data are compiled from the following standard references: gene symbol from HGNC; chromosomal locus, locus name, critical region, complementation group from OMIM; protein name from UniProt. For a description of databases (Locus Specific, HGMD) to which links are provided, click here.Table B. OMIM Entries for Duane Syndrome (View All in OMIM) View in own window 118423CHIMERIN 1; CHN1 126800DUANE RETRACTION SYNDROME 1; DURS1 604356DUANE RETRACTION SYNDROME 2; DURS2Normal allelic variants. Alternatively spliced transcript variants encoding different isoforms have been described for this gene (see Table A, Gene Symbol). The longest CHN1 transcript variant (NM_001822.5) has 13 exons. Pathologic allelic variants. Ten different heterozygous missense changes have been identified in CHN1 [Miyake et al 2008, Chan et al 2011, Miyake et al 2011]. All ten nucleotide substitutions cosegregated with the affected haplotypes. None were present in online single nucleotide databases or on 788 control chromosomes. Six of the ten resulted in non-conservative amino acid substitutions. All were predicted to alter amino acids that are conserved in CHN1 orthologs of eight different species. Recently Miyake et al [2011] described the mutation NM_001822.5:c.443A>T; NP_001813.1:p.Tyr148Phe which expands the phenotypic spectrum of hyperactivating CHN1 mutations.Normal gene product. There are multiple N-chimaerin isoforms. N-chimaerin has three domains: an N-terminal SH2 domain, a C-terminal RhoGAP domain, and a central C1 domain similar to protein kinase C. No mutations have been identified in the N-terminal SH2 domain. The longest isoform NP_001813.1 has 459 amino acid residues.Abnormal gene product. All identified mutations act as gain-of-function mutations that increase N-chimaerin (α2-chimerin RacGAP) activity in vitro. Several mutations appear to enhance N-chimaerin translocation to the cell membrane or enhance its ability to self-associate. To test the hypothesis that N-chimaerin overactivity results in aberrant axon development in vivo, a chick in ovo system was used to overexpress wildtype and mutant alpha-2-chimerin in the embryonic ocular motor nucleus [Miyake et al 2008]. In the majority (71%-87%) of embryos overexpressing wildtype or mutant constructs, the oculomotor nerve stalled and its axons terminated prematurely adjacent to the dorsal rectus muscle. It is possible with the p.Tyr148Phe amino acid substitution reported by Miyake et al [2011] that the variable phenotype is a result of both hyperactivation of α2-chimerin and interaction of its SH2 of Rac-GAP domains with other proteins.