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Proceedings of the National Academy of... Sep 2012Eye movements depend on correct patterns of connectivity between cranial motor axons and the extraocular muscles. Despite the clinical importance of the ocular motor...
Eye movements depend on correct patterns of connectivity between cranial motor axons and the extraocular muscles. Despite the clinical importance of the ocular motor system, little is known of the molecular mechanisms underlying its development. We have recently shown that mutations in the Chimaerin-1 gene encoding the signaling protein α2-chimaerin (α2-chn) perturb axon guidance in the ocular motor system and lead to the human eye movement disorder, Duane retraction syndrome (DRS). The axon guidance cues that lie upstream of α2-chn are unknown; here we identify candidates to be the Semaphorins (Sema) 3A and 3C, acting via the PlexinA receptors. Sema3A/C are expressed in and around the developing extraocular muscles and cause growth cone collapse of oculomotor neurons in vitro. Furthermore, RNAi knockdown of α2-chn or PlexinAs in oculomotor neurons abrogates Sema3A/C-dependent growth cone collapse. In vivo knockdown of endogenous PlexinAs or α2-chn function results in stereotypical oculomotor axon guidance defects, which are reminiscent of DRS, whereas expression of α2-chn gain-of-function constructs can rescue PlexinA loss of function. These data suggest that α2-chn mediates Sema3-PlexinA repellent signaling. We further show that α2-chn is required for oculomotor neurons to respond to CXCL12 and hepatocyte growth factor (HGF), which are growth promoting and chemoattractant during oculomotor axon guidance. α2-chn is therefore a potential integrator of different types of guidance information to orchestrate ocular motor pathfinding. DRS phenotypes can result from incorrect regulation of this signaling pathway.
Topics: Animals; Chemokine CXCL12; Chick Embryo; Chimerin 1; Duane Retraction Syndrome; Gene Knockdown Techniques; Growth Cones; Hepatocyte Growth Factor; Immunohistochemistry; In Situ Hybridization; Oculomotor Muscles; RNA Interference; Receptors, Cell Surface; Semaphorin-3A; Signal Transduction
PubMed: 22912401
DOI: 10.1073/pnas.1116481109 -
Case Reports in Ophthalmology 2022Idiopathic intracranial hypertension (IIH) is a poorly understood condition, and its presentation can coexist with other diseases. Simultaneous IIH and Duane retraction...
Idiopathic intracranial hypertension (IIH) is a poorly understood condition, and its presentation can coexist with other diseases. Simultaneous IIH and Duane retraction syndrome (DRS) type 1 have never been reported to coexist in an adult patient. Herein, we report a 32-year-old obese female with a history of chronic renal failure who had a renal transplant rejection 6 years prior to presentation and was treated with oral steroids and immunosuppressive medications. She began to experience signs and symptoms of increased intracranial pressure (morning headache and binocular horizontal diplopia) and had limited abduction of one eye on examination. The case was later diagnosed as IIH with DRS type 1.
PubMed: 35702521
DOI: 10.1159/000524363 -
Indian Journal of Ophthalmology Mar 2015
Topics: Duane Retraction Syndrome; Esotropia; Female; Humans; Male; Oculomotor Muscles; Ophthalmologic Surgical Procedures; Vision, Binocular
PubMed: 25971189
DOI: 10.4103/0301-4738.156970 -
Journal of Research in Medical Sciences... 2020Duane's retraction syndrome is a congenital eye movement anomaly with narrowing of the palpebral fissure and globe retraction on attempted adduction. There are several...
Unilateral medial rectus muscle recession combined lateral rectus muscle marginal myotomy for the treatment of Duane's retraction syndrome: A promising surgical procedure.
BACKGROUND
Duane's retraction syndrome is a congenital eye movement anomaly with narrowing of the palpebral fissure and globe retraction on attempted adduction. There are several surgical approaches to treat the narrowing of the palpebral fissure. The purpose of the present study was to evaluate the efficacy of unilateral medial rectus recession (MRR) muscle combined lateral rectus (LR) muscle marginal myotomy (MM) with unilateral MRR alone in the management of narrowing of the palpebral fissure of patients with Type 1 Duane's retraction syndrome (DRS).
MATERIALS AND METHODS
Twenty-eight patients with unilateral DRS Type 1 were randomly divided into two groups (14 eyes of 14 patients in each group). Age ≥5 years with DRS Type 1 with <20 prism diopters in primary position who were candidates for surgery were consecutively enrolled in this randomized controlled trial. Patients were divided into treatment groups to receive unilateral MR recession with simultaneous MM group or with unilateral MR recession alone. The amount of deviation in primary position, abnormal head position, palpebral fissure width (PFW), and up/down shoot was evaluated before and 3 months after the surgery. This study was registered at the Iranian Registry of Clinical Trials under the registration code IRCT20131229015975N3.
RESULTS
PFW increased within MRR/MM group at the end of the study (8.86 ± 1.51) compared with the baseline (7.79 ± 1.48) ( < 0.001). In contrast, in the MRR/MM group, PFW did not increase statistically significantly within the MRR group at the end of the study (8.14 ± 1.35) compared with the baseline (8.07 ± 1.38) ( = 0.67). Mean ± standard deviation of PFW (mm) in MRR/MM group after surgery (8.86 ± 1.51) was statistically significantly higher than that in the MRR group (8.14 ± 1.35), ( = 0.002).
CONCLUSION
The results of our study demonstrate PFW significantly increased after unilateral MRR muscle combined LR muscle MM.
PubMed: 32765624
DOI: 10.4103/jrms.JRMS_836_19 -
Vision Research Sep 2008Disconjugate oculomotor adaptation is driven by the need to maintain binocular vision. Since binocular vision in Duane Retraction Syndrome (DRS) patients is normal in...
Disconjugate oculomotor adaptation is driven by the need to maintain binocular vision. Since binocular vision in Duane Retraction Syndrome (DRS) patients is normal in half of their horizontal field of gaze (i.e., sound-side of gaze), we wondered whether oculomotor adaptive capabilities are efficient despite such a severe impairment of eye motility towards the other half of the horizontal field of gaze (i.e., affected-side gaze). We compared properties of horizontal saccades of patients with congenital unilateral Duane Retraction Syndrome type I in binocular viewing and monocular viewing conditions by simultaneously recording both eyes with the search coil technique. Our results show a mismatch between the pulse and the step signal of the innervation for saccades. When tested in the affected eye viewing condition (sound eye covered), the eyes showed not only similarly-directed increases of the saccadic gain (pulse signal) in the two eyes but also disjunctive post-saccadic drifts (step signal). This behavior suggests that visuomotor errors presented only to the affected eye were transferred to the sound eye, producing conjugate changes of the saccadic command. The post-saccadic command remained unchanged, however, and controlled the final position of each eye separately. This suggests that monocular adaptation is possible only for the step of innervation (i.e., controlling the final eye position) but not for the pulse of innervation (i.e., controlling the saccadic gain), even though the peculiarity of unilateral DRS type I offers a clear advantage for separate pathways of control for the two eyes.
Topics: Adaptation, Physiological; Duane Retraction Syndrome; Eye Movement Measurements; Fixation, Ocular; Humans; Neural Pathways; Photic Stimulation; Saccades; Vision, Binocular; Vision, Monocular
PubMed: 18606179
DOI: 10.1016/j.visres.2008.06.007 -
Indian Journal of Ophthalmology Feb 2017High-resolution magnetic resonance imaging (MRI) of intracranial parts of sixth nerve and seventh nerve and the extraocular muscles (EOMs) in orbit to correlate the...
PURPOSE
High-resolution magnetic resonance imaging (MRI) of intracranial parts of sixth nerve and seventh nerve and the extraocular muscles (EOMs) in orbit to correlate the clinical characteristics in patients with two special forms of strabismus in congenital cranial dysinnervation disorders which are Duane's retraction syndrome (DRS) and Mobius syndrome.
MATERIALS AND METHODS
Morphological analysis by 3T MRI of orbit (using surface coils) and brain (using 32 channel head coil) was performed on 6 patients with clinical DRS (1 bilateral), 2 cases with Mobius syndrome, and 1 case with congenital sixth nerve palsy. These were compared with findings in five controls.
RESULTS
We observed absence/hypoplasia of sixth nerve in five out of seven eyes with DRS (71.42%), anomalous course in one eye, sixth and seventh nerve absence/hypoplasia in affected eyes with Mobius syndrome and bilateral absence/hypoplasia of the sixth nerve in congenital sixth nerve palsy. For EOMs we calculated maximum diameter, area, and circumference of muscles using Osirix software, and noticed significant hypoplasia of lateral rectus in comparison to controls (P < 0.001).
CONCLUSIONS
MRI gives useful information regarding confirmation of clinical diagnosis and its neurological anomalies in complex cases and helps to plan tailor made surgical management.
Topics: Abducens Nerve; Abducens Nerve Diseases; Abnormalities, Multiple; Duane Retraction Syndrome; Humans; Imaging, Three-Dimensional; Magnetic Resonance Imaging; Mobius Syndrome; Oculomotor Muscles; Orbit; Pilot Projects
PubMed: 28345573
DOI: 10.4103/ijo.IJO_1013_15 -
Eye (London, England) Oct 2013To report the postoperative results of full-tendon vertical rectus transposition (VRT) augmented with lateral fixation suture for the treatment of type 1 Duane syndrome...
PURPOSE
To report the postoperative results of full-tendon vertical rectus transposition (VRT) augmented with lateral fixation suture for the treatment of type 1 Duane syndrome and sixth nerve palsy and to determine whether there was a decrease in the effect of the Foster suture over time.
METHODS
This retrospective, consecutive case series included patients who underwent a full-tendon VRT transposition with lateral fixation for type 1 Duane syndrome or sixth nerve palsy. The primary outcome measures included deviation, abnormal head posture(AHP), abduction deficiency, and postoperative binocular single visual field (BSVF).
RESULTS
Eighty-seven patients (87 eyes: 40 eyes with Duane syndrome and 47 eyes with sixth nerve palsy) were included in this study. In Duane syndrome patients, the deviation was reduced by a mean of 95%, the AHP was eliminated in 86% of patients, the abduction was improved by 42%, and a useful BSVF of ≈ 67% of normal was achieved at 1 year post operation. In sixth nerve palsy patients, the deviation was reduced by 99%, the abduction was improved by 59%, and a useful BSVF of ≈ 71% of normal was achieved at 1 year post operation. In both groups, the improvements in deviation angle and abduction were stable postoperatively. Sixteen patients needed reoperation for undercorrection.
CONCLUSION
VRT surgery with posterior fixation is an effective treatment method for complete sixth nerve palsy and Duane syndrome with esotropia, AHP, and abduction deficiency. The procedure carries a small risk of reoperation for undercorrection. The effect of the Foster suture did not decline over time.
Topics: Abducens Nerve Diseases; Adolescent; Adult; Aged; Child; Child, Preschool; Duane Retraction Syndrome; Esotropia; Female; Humans; Male; Middle Aged; Oculomotor Muscles; Ophthalmologic Surgical Procedures; Retrospective Studies; Suture Techniques; Tendon Transfer; Young Adult
PubMed: 23907625
DOI: 10.1038/eye.2013.167 -
Investigative Ophthalmology & Visual... Dec 2007The authors used magnetic resonance imaging (MRI) to study extraocular muscles (EOMs) and nerves in Duane-radial ray (Okihiro) syndrome (DRRS) caused by mutations in the...
PURPOSE
The authors used magnetic resonance imaging (MRI) to study extraocular muscles (EOMs) and nerves in Duane-radial ray (Okihiro) syndrome (DRRS) caused by mutations in the transcription factor SALL4.
METHODS
The authors examined four male and two female affected members of a pedigree previously reported to cosegregate DRRS and a heterozygous SALL4 mutation. Coronal T1-weighted magnetic resonance images of the orbits and heavily T2-weighted images in the plane of the cranial nerves were obtained in four subjects. MRI findings were correlated with motility examinations and published norms obtained using identical technique.
RESULTS
Five of the six subjects with DRRS had radial ray abnormalities including thumb, radial artery, radial bone, and pectoral muscle hypoplasia. Three had bilateral and three had unilateral ocular involvement. Seven eyes had limitation of both abduction and adduction, whereas two had limitations only of abduction. Most affected eyes had lid fissure narrowing and retraction in adduction. Intraorbital and intracranial abducens nerves (CN6) were small to absent, particularly ipsilateral to abduction deficiency. All subjects undergoing MRI had normal intracranial oculomotor nerves (CN3). Optic nerve (ON) cross-section findings were similar to normal. EOMs and pulleys were structurally normal in most subjects. In some affected orbits, a branch of CN3 closely approximated and presumably innervated the LR.
CONCLUSIONS
DRRS encompasses a Duane syndrome phenotype, with a variable and asymmetric endophenotype including marked CN6 hypoplasia and probable innervation or coinnervation of the LR by CN3. This endophenotype is more limited than reported in DURS2-linked Duane syndrome (On-line Mendelian Inheritance in Man, OMIM 604356) and CFEOM1 (OMIM 135700), which are clinically similar congenital cranial dysinnervation disorders that also feature CN3 hypoplasia and more widespread EOM abnormalities.
Topics: Abducens Nerve Diseases; Adolescent; Adult; Aged; Duane Retraction Syndrome; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Mutation; Oculomotor Muscles; Oculomotor Nerve Diseases; Optic Nerve; Orbit; Pedigree; Phenotype; Radial Neuropathy; Transcription Factors; Zinc Fingers
PubMed: 18055799
DOI: 10.1167/iovs.07-0772 -
Turkish Journal of Ophthalmology Aug 2017To determine the most common ocular causes and types of abnormal head position (AHP) and describe their clinical features.
OBJECTIVES
To determine the most common ocular causes and types of abnormal head position (AHP) and describe their clinical features.
MATERIALS AND METHODS
Patients with AHP who had been followed in the strabismus unit were retrospectively reviewed. Demographic features and orthoptic characteristics were recorded.
RESULTS
A total of 163 patients including 61 women (37.4%) and 102 men (62.6%), with a mean age of 19.9±18.3 were recruited. The most common causes of AHP were determined as fourth cranial nerve palsy (33.7%), Duane retraction syndrome (21.5%), sixth cranial nerve palsy (11%), nystagmus blockage syndrome (9.8%) and Brown syndrome (6.7%). Other less frequent causes were A-V pattern strabismus, comitant strabismus, thyroid orbitopathy and third cranial nerve palsy. The most common types of AHP were head tilt (45.4%) and face turn (36.8%). Out of 142 patients whose visual acuity could be evaluated, 28.2% had amblyopia. The frequency of amblyopia varied depending on the diagnosis (p<0.001), while there was no relation between amblyopia and different types of AHP (p=0.497). Stereopsis and fusion could be tested in 128 patients and 43.8% of them had stereopsis and fusion. The presence of stereopsis and fusion was found to be related with the diagnosis (p=0.001), whereas it was not related with the types of AHP (p=0.580). The presence of amblyopia was not significantly associated with fusion (p=1.000) or stereopsis (p=0.602).
CONCLUSION
There are many ocular pathologies that cause AHP. Patients with similar diagnoses may have different types of AHP. Patients may have amblyopia and impaired binocularity despite AHP. Therefore, all patients with AHP should be examined in detail and these points should be considered in the treatment plan.
PubMed: 28845325
DOI: 10.4274/tjo.42068 -
The Journal of Clinical Investigation May 2017Duane retraction syndrome (DRS) is the most common form of congenital paralytic strabismus in humans and can result from α2-chimaerin (CHN1) missense mutations. We...
Duane retraction syndrome (DRS) is the most common form of congenital paralytic strabismus in humans and can result from α2-chimaerin (CHN1) missense mutations. We report a knockin α2-chimaerin mouse (Chn1KI/KI) that models DRS. Whole embryo imaging of Chn1KI/KI mice revealed stalled abducens nerve growth and selective trochlear and first cervical spinal nerve guidance abnormalities. Stalled abducens nerve bundles did not reach the orbit, resulting in secondary aberrant misinnervation of the lateral rectus muscle by the oculomotor nerve. By contrast, Chn1KO/KO mice did not have DRS, and embryos displayed abducens nerve wandering distinct from the Chn1KI/KI phenotype. Murine embryos lacking EPH receptor A4 (Epha4KO/KO), which is upstream of α2-chimaerin in corticospinal neurons, exhibited similar abducens wandering that paralleled previously reported gait alterations in Chn1KO/KO and Epha4KO/KO adult mice. Findings from Chn1KI/KI Epha4KO/KO mice demonstrated that mutant α2-chimaerin and EphA4 have different genetic interactions in distinct motor neuron pools: abducens neurons use bidirectional ephrin signaling via mutant α2-chimaerin to direct growth, while cervical spinal neurons use only ephrin forward signaling, and trochlear neurons do not use ephrin signaling. These findings reveal a role for ephrin bidirectional signaling upstream of mutant α2-chimaerin in DRS, which may contribute to the selective vulnerability of abducens motor neurons in this disorder.
Topics: Animals; Cerebral Cortex; Chimerin 1; Duane Retraction Syndrome; Embryo, Mammalian; Humans; Mice; Mice, Knockout; Motor Neurons; Receptor, EphA4; Signal Transduction; Spinal Cord
PubMed: 28346224
DOI: 10.1172/JCI88502