-
The Journal of Neuroscience : the... Aug 2021A precise sequence of axon guidance events is required for the development of the ocular motor system. Three cranial nerves grow toward, and connect with, six...
A precise sequence of axon guidance events is required for the development of the ocular motor system. Three cranial nerves grow toward, and connect with, six extraocular muscles in a stereotyped pattern, to control eye movements. The signaling protein alpha2-chimaerin (α2-CHN) plays a pivotal role in the formation of the ocular motor system; mutations in , encoding α2-CHN, cause the human eye movement disorder Duane Retraction Syndrome (DRS). Our research has demonstrated that the manipulation of α2-chn signaling in the zebrafish embryo leads to ocular motor axon wiring defects, although the signaling cascades regulated by α2-chn remain poorly understood. Here, we demonstrate that several cytoskeletal regulatory proteins-collapsin response mediator protein 2 (CRMP2; encoded by the gene ), stathmin1, and stathmin 2-bind to α2-CHN. , , and especially are expressed by ocular motor neurons. We find that the manipulation of and of in zebrafish larvae leads to defects in both the axon wiring of the ocular motor system and the optokinetic reflex, impairing horizontal eye movements. Knockdowns of these molecules in zebrafish larvae of either sex caused axon guidance phenotypes that included defasciculation and ectopic branching; in some cases, these phenotypes were reminiscent of DRS. knock-down phenotypes were rescued by the overexpression of CRMP2 and STMN1, suggesting that these proteins act in the same signaling pathway. These findings suggest that CRMP2 and stathmins signal downstream of α2-CHN to orchestrate ocular motor axon guidance and to control eye movements. The precise control of eye movements is crucial for the life of vertebrate animals, including humans. In humans, this control depends on the arrangement of nerve wiring of the ocular motor system, composed of three nerves and six muscles, a system that is conserved across vertebrate phyla. Mutations in the protein alpha2-chimaerin have previously been shown to cause eye movement disorders (squint) and axon wiring defects in humans. Our recent work has unraveled how alpha2-chimaerin coordinates axon guidance of the ocular motor system in animal models. In this article, we demonstrate key roles for the proteins CRMP2 and stathmin 1/2 in the signaling pathway orchestrated by alpha2-chimaerin, potentially giving insight into the etiology of eye movement disorders in humans.
Topics: Animals; Axon Guidance; Chimerin 1; Duane Retraction Syndrome; Eye Movements; Motor Neurons; Nerve Tissue Proteins; Oculomotor Muscles; Signal Transduction; Stathmin; Zebrafish; Zebrafish Proteins
PubMed: 34168008
DOI: 10.1523/JNEUROSCI.0983-19.2021 -
Cureus Jun 2021Objective In this study, we aimed to investigate the prevalence of diplopia in cases with type 1 Duane retraction syndrome (DRS). Materials and methods This study was a...
Objective In this study, we aimed to investigate the prevalence of diplopia in cases with type 1 Duane retraction syndrome (DRS). Materials and methods This study was a retrospective review of cases involving patients presenting diagnosed with DRS over a period of 24 years. Among these cases, 28 had type 1 DRS and fulfilled the inclusion criteria. The cases were evaluated in terms of age, gender, affected eye, concomitant ocular motility disorders, presence of amblyopia, manifest shift, abnormal head position (AHP), fusion, and stereopsis. Results Sixteen of the patients (57.1%) in the study were female, and 12 (42.8%) were male; the mean age of the patients was 18.9 years (range: 7-67 years). The right eye was affected in six of the cases (21.4%), and the left eye in 22 (78.6%) of the cases. On examination, diplopia was not observed in 21 (75%) cases, but it was detected in seven (25%). AHP was present in five of the seven cases with diplopia and not present in two, and all seven of the diplopic cases had fusion, while three had stereopsis. The level of stereopsis in all diplopic cases was 400 sn/ark. When the clinical findings of patients with diplopia and those without diplopia were compared, a statistically significant difference was observed only in terms of AHP. Conclusions Although diplopia is not one of the clinical features of DRS, it must be noted that in cases with type 1 DRS, diplopia may occur in directions in which the movement of the eyeball is limited. In the presence of this finding, which might mimic sixth nerve palsy, patient history must be diligently taken, other clinical findings of DRS must be thoroughly examined, and an MRI should be performed when necessary for an easier diagnosis.
PubMed: 34164253
DOI: 10.7759/cureus.15769 -
Nephron 2021The MAFB gene encodes an important basic leucine zipper transcription factor that functions in glomerular podocytes, macrophages, and osteoclasts. Recently, MAFB was...
The MAFB gene encodes an important basic leucine zipper transcription factor that functions in glomerular podocytes, macrophages, and osteoclasts. Recently, MAFB was identified as the gene that was responsible for causing nephropathy with focal segmental glomerulosclerosis (FSGS) with multicentric carpotarsal osteolysis (MCTO) or Duane retraction syndrome (DRS). Here, we describe a patient with nephropathy associated with FSGS who exhibited a novel stop-gain variant in the MAFB gene (NM_005461:c.590C>A (p.Ser197Ter)). The patient's father exhibited proteinuria with FSGS with possible DRS, whereas the patient exhibited nephropathy with FSGS and nearly normal eye movement and hearing function, as well as intact bone structure in the extremities. Conventional oral steroids or immunosuppressive drugs have not demonstrated effectiveness for patients with nephropathy who exhibit pathogenic variants in MAFB, except for a patient with nephropathy with FSGS and MCTO who experienced attenuated proteinuria within the subnephrotic range in response to cyclosporine A (CyA) treatment for at least 4 years. Thus, we attempted administration of CyA in our patient. Unexpectedly, the patient demonstrated good and rapid responses to CyA, including a partial reduction in proteinuria from approximately 2.0 g/g Cr to proteinuria within the subnephrotic range (0.27 g/g Cr) after 13 months of observation. Our findings suggest that CyA may be a suitable treatment option for patients with nephropathy with FSGS who exhibit pathogenic MAFB variants.
Topics: Adult; Age of Onset; Cyclosporine; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; MafB Transcription Factor; Male; Ocular Motility Disorders
PubMed: 33975323
DOI: 10.1159/000516248 -
Ophthalmic Genetics Oct 2021: Duane retraction syndrome and arthrogryposis multiplex congenita have an incidence of approximately 1:1500-1:3000 live births. However, the association of these two...
A 7-year old female with arthrogryposis multiplex congenita, Duane retraction syndrome, and Marcus Gunn phenomenon due to a ZC4H2 gene mutation: a clinical presentation of the Wieacker-Wolff syndrome.
: Duane retraction syndrome and arthrogryposis multiplex congenita have an incidence of approximately 1:1500-1:3000 live births. However, the association of these two entities with a Marcus-Gunn might be a rare and, until now, under-recognized clinical presentation of the Wieacker-Wolff Syndrome.: We report a 7-year-old female with dysmorphic features, global developmental delay, arthrogryposis multiplex congenita (AMC), Duane retraction syndrome (DRS), and unilateral Marcus Gunn jaw winking.: Whole Exome Sequencing showed a de novo premature stop codon in ZC4H2. Extensive genetic and metabolic work was negative otherwise and Brain MRI showed delayed non-specific myelination abnormalities. She continues to have significant delays but does not have regression, seizures or other neurological complications. She has required a multidisciplinary approach for the management of her multiple contractures.: This case confirms ZC4H2 as a cause of syndromic DRS and extends the ZC4H2 phenotype to include Marcus Gunn jaw winking.
Topics: Apraxias; Arthrogryposis; Blepharoptosis; Child; Codon, Nonsense; Contracture; Duane Retraction Syndrome; Female; Genetic Diseases, X-Linked; Heart Defects, Congenital; Humans; Intracellular Signaling Peptides and Proteins; Jaw Abnormalities; Magnetic Resonance Imaging; Muscular Atrophy; Mutation; Nervous System Diseases; Nuclear Proteins; Ophthalmoplegia; Reflex, Abnormal; Exome Sequencing
PubMed: 33949289
DOI: 10.1080/13816810.2021.1923040 -
Journal of AAPOS : the Official... Apr 2021A 19-year-old man with Loeys-Dietz syndrome and right exotropic Duane syndrome after bilateral lateral rectus recessions at age 22 months presented with recurrent... (Review)
Review
A 19-year-old man with Loeys-Dietz syndrome and right exotropic Duane syndrome after bilateral lateral rectus recessions at age 22 months presented with recurrent progressive exotropia 17 years after his initial surgery. Surgical correction was aborted intraoperatively when extreme atrophy of the right medial rectus, lateral rectus, and superior rectus muscles was observed, later corroborated by orbital magnetic resonance imaging.
Topics: Atrophy; Duane Retraction Syndrome; Exotropia; Humans; Loeys-Dietz Syndrome; Male; Oculomotor Muscles; Ophthalmologic Surgical Procedures; Young Adult
PubMed: 33675960
DOI: 10.1016/j.jaapos.2020.11.010 -
European Journal of Medical Genetics Apr 2021Duane retraction syndrome is a congenital eye movement disorder characterized by a failure of abducens nerve to develop normally, resulting in restriction or absence of...
Duane retraction syndrome is a congenital eye movement disorder characterized by a failure of 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. There is a genetic heterogeneity in Duane retraction syndrome (DURS). DURS maps to chromosome 8q13 in some patients, and pathogenic variants in CHN1 and MAFB genes are known to lead to DURS. We report here a child and his father with Duane retraction syndrome, associated to swallowing difficulties and unilateral trapeze aplasia. A whole exome sequencing revealed a heterozygous missense variant in CHN1 gene. This gene encodes GTPase-activating protein and is involved in the assembly of neuronal locomotor circuits. A patient with a 8q deletion has previously been described with a Duane retraction syndrome associated to trapeze aplasia. We provide an additional description to support the role in cranial nerves development of the CHN1 gene.
Topics: Child; Chimerin 1; Cranial Nerves; Deglutition; Duane Retraction Syndrome; Humans; Male; Middle Aged; Mutation, Missense; Pedigree; Phenotype
PubMed: 33667650
DOI: 10.1016/j.ejmg.2021.104188 -
Journal of Binocular Vision and Ocular... 2021: To evaluate the outcome of augmented superior rectus transposition (SRT) with medial rectus (MR) recession in patients with Duane Retraction Syndrome (DRS) and sixth...
: To evaluate the outcome of augmented superior rectus transposition (SRT) with medial rectus (MR) recession in patients with Duane Retraction Syndrome (DRS) and sixth nerve palsy.: Twenty four patients (16 DRS and 8 sixth nerve palsy) that underwent the procedure were included. The superior rectus muscle was secured, detached, and re-attached to the sclera along the spiral of Tilaux, adjacent to lateral rectus insertion. A non-absorbable augmentation suture was passed through the sclera, 8 mm posterior to the insertion of the lateral rectus.: At the last follow-up, the effect of surgery in decreasing esotropia in both groups was significant ( = .001 for DRS group, = .002 for sixth nerve palsy). In both groups, abduction deficit improved significantly ( < .001 for DRS and = .008 for sixth nerve palsy). After the surgery, small, asymptomatic vertical deviation in primary position was induced in five patients (20.8%). Post-operatively, none of the patients complained of torsional diplopia. In the 6-month follow-up, compared with the first postoperative visit, an eso-drift at distance or near developed in 11 patients (45.8%). Of the 11 patients with eso-drift, overcorrection (exotropia of 3-14 PD) was present at the first post-operative visit in 5 cases. Four cases showed an exo-drift (2-5 PD) at distance or near over time.: SRT with medial rectus recession improves esotropia and abduction limitation without inducing significant vertical deviations and torsional diplopia. Some of the cases that underwent SRT with MR recession may show an eso-drift. The eso-drift can correct initial exotropia in some cases.
Topics: Abducens Nerve Diseases; Duane Retraction Syndrome; Eye Movements; Humans; Ophthalmologic Surgical Procedures; Retrospective Studies
PubMed: 33666529
DOI: 10.1080/2576117X.2021.1879985 -
Journal of AAPOS : the Official... Apr 2021Orbital myositis is a rare, commonly idiopathic, inflammatory condition that affects one or more extraocular muscles. We present a case of unilateral orbital myositis...
Orbital myositis is a rare, commonly idiopathic, inflammatory condition that affects one or more extraocular muscles. We present a case of unilateral orbital myositis affecting the lateral rectus muscle presenting with gaze-evoked amaurosis, pain, and diplopia, with restrictive limitation of adduction. With improvement in adduction after initiating treatment, we noted narrowing of the palpebral fissure on attempted adduction, mimicking Duane retraction syndrome (DRS). Reported cases of "pseudo-DRS" are associated with multiple etiologies and are characterized by retraction on attempted abduction rather than adduction, as occurs in true DRS. In this case, pseudo-DRS occurred in the setting of idiopathic orbital inflammatory syndrome (orbital myositis) with a motility pattern more consistent with true DRS.
Topics: Diplopia; Duane Retraction Syndrome; Eyelids; Humans; Oculomotor Muscles; Orbital Myositis
PubMed: 33652102
DOI: 10.1016/j.jaapos.2020.11.012 -
Journal of AAPOS : the Official... Feb 2021To present the clinical features of 4 patients with Duane retraction syndrome characterized by synergistic divergence or convergence, abnormal vertical movements, and...
PURPOSE
To present the clinical features of 4 patients with Duane retraction syndrome characterized by synergistic divergence or convergence, abnormal vertical movements, and accessory fibrotic bands.
METHODS
The medical records of 4 patients were reviewed retrospectively for the following clinical manifestations: visual acuity, refraction, ocular alignments, ocular motility, head position, magnetic resonance imaging, surgical techniques, and outcomes.
RESULTS
All 4 cases were diagnosed as variants of Duane retraction syndrome. Two cases (cases 1 and 2) had synergistic divergence with unilateral adduction deficit, and 2 (cases 3 and 4) had synergistic convergence with bilateral abduction deficit. Case 2 manifested abnormal vertical movements of the right eye, which goes down with adduction of the left eye and goes up oppositely with abduction of left eye. Accessory fibrotic bands were detected beside the medial rectus muscle of both eyes in case 3. Synergistic convergence in case 4 occurred only after the first strabismus surgery. Weakening of the misinnervated horizontal rectus muscle improved ocular alignment and head position in cases 1, 3, and 4.
CONCLUSIONS
Synergistic divergence and convergence are extremely rare and may present with a great diversity of clinical features. A good outcome is very difficult to achieve; however, weakening of the misinnervated horizontal rectus muscle was therapeutic in these patients.
Topics: Duane Retraction Syndrome; Humans; Oculomotor Muscles; Ophthalmologic Surgical Procedures; Retrospective Studies; Strabismus
PubMed: 33607271
DOI: 10.1016/j.jaapos.2020.10.007 -
Journal of AAPOS : the Official... Apr 2021Superior rectus transposition with medial rectus recession is commonly performed for unilateral esotropic Duane syndrome. For bilateral esotropic Duane syndrome,...
Superior rectus transposition with medial rectus recession is commonly performed for unilateral esotropic Duane syndrome. For bilateral esotropic Duane syndrome, bilateral medial rectus recession is the most frequently performed surgery and usually provides satisfactory alignment in primary position; however, there is limited improvement in abduction. We report the outcomes of bilateral augmented superior rectus transposition and medial rectus recession in 4 patients with bilateral esotropic Duane syndrome. Postoperatively, abduction was improved in all patients; 3 were orthotropic in the primary position, and 1 had residual esotropia.
Topics: Duane Retraction Syndrome; Esotropia; Humans; Oculomotor Muscles; Ophthalmologic Surgical Procedures; Retrospective Studies; Vision, Binocular
PubMed: 33601043
DOI: 10.1016/j.jaapos.2020.11.006