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American Journal of Human Genetics Dec 1999Duane retraction syndrome (DRS) is a congenital eye-movement disorder characterized by a failure of cranial nerve VI (the abducens nerve) to develop normally, resulting...
Duane retraction syndrome (DRS) 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, restricted adduction, and narrowing of the palpebral fissure and retraction of the globe on attempted adduction. DRS has a prevalence of approximately 0.1% in the general population and accounts for 5% of all strabismus cases. Undiagnosed DRS in children can lead to amblyopia, a permanent uncorrectable loss of vision. A large family with autosomal dominant DRS was examined and tested for genetic linkage. After exclusion of candidate regions previously associated with DRS, a genomewide search with highly polymorphic microsatellite markers was performed, and significant evidence for linkage was obtained at chromosome 2q31 (D2S2314 maximum LOD score 11.73 at maximum recombination fraction. 0). Haplotype analysis places the affected gene in a 17.8-cM region between the markers D2S2330 and D2S364. No recombinants were seen with markers between these two loci. The linked region contains the homeobox D gene cluster. Three of the genes within this cluster, known to participate in hindbrain development, were sequenced in affected and control individuals. Coding sequences for these genes were normal or had genetic alterations unlikely to be responsible for the DRS phenotype. Identifying the gene responsible for DRS may lead to an improved understanding of early cranial-nerve development.
Topics: Amino Acid Substitution; Chromosome Mapping; Chromosomes, Human, Pair 2; Codon; DNA Mutational Analysis; Duane Retraction Syndrome; Female; Genes, Dominant; Genes, Homeobox; Genotype; Haplotypes; Humans; Lod Score; Male; Mexico; Microsatellite Repeats; Mutation; Pedigree; Penetrance
PubMed: 10577917
DOI: 10.1086/302656 -
Kidney International Aug 2018Focal segmental glomerulosclerosis (FSGS) is a leading cause of end-stage renal disease in children and adults. Genetic factors significantly contribute to early-onset...
Focal segmental glomerulosclerosis (FSGS) is a leading cause of end-stage renal disease in children and adults. Genetic factors significantly contribute to early-onset FSGS, but the etiologies of most adult cases remain unknown. Genetic studies of monogenic syndromic FSGS exhibiting extra-renal manifestations have uncovered an unexpected biological role for genes in the development of both podocytes and other cellular lineages. To help define these roles, we studied two unrelated families with FSGS associated with Duane Retraction Syndrome, characterized by impaired horizontal eye movement due to cranial nerve malformation. All four affected individuals developed FSGS and Duane Retraction Syndrome in their first to second decade of life, manifested as restricted abduction together with globe retraction and narrowed palpebral fissure on attempted adduction. Hypoplasia of the abducens nerves and hearing impairment occurred in severely affected individuals. Genetic analyses revealed that affected individuals harbor a rare heterozygous substitution (p.Leu239Pro) in MAFB, a leucine zipper transcription factor. Luciferase assays with cultured monocytes indicated that the substitution significantly reduced transactivation of the F4/80 promoter, the known MAFB recognition element. Additionally, immunohistochemistry indicated reduced MAFB expression in the podocytes of patients. Structural modeling suggested that the p.Leu239Pro substitution in the DNA-binding domain possibly interferes with the stability of the adjacent zinc finger. Lastly, podocytes in neonatal mice with p.Leu239Pro displayed impaired differentiation. Thus, MAFB mutations impair development and/or maintenance of podocytes, abducens neurons and the inner ear. The interactions between MAFB and regulatory elements in these developing organs are likely highly specific based on spatiotemporal requirements.
Topics: Adolescent; Adult; Age of Onset; Amino Acid Substitution; Animals; Child; Duane Retraction Syndrome; Female; Genetic Testing; Glomerulosclerosis, Focal Segmental; Heterozygote; Humans; Kidney Failure, Chronic; MafB Transcription Factor; Male; Mice; Mutation; Podocytes; Protein Domains; Sequence Homology, Amino Acid; Young Adult
PubMed: 29779709
DOI: 10.1016/j.kint.2018.02.025 -
Korean Journal of Ophthalmology : KJO Dec 2009We report a case of pseudo-Duane's retraction syndrome with entrapment of the medial rectus muscle in an old medial orbital wall fracture presenting identical clinical...
We report a case of pseudo-Duane's retraction syndrome with entrapment of the medial rectus muscle in an old medial orbital wall fracture presenting identical clinical symptoms as Duane's retraction syndrome. A 15-year-old boy presented with persistent limited right eye movement since a young age. Examination showed marked limited abduction, mildly limited adduction, and globe retraction accompanied by narrowing of the palpebral fissure during attempted adduction in the right eye. He showed a right esotropia of 16 prism diopters and his head turned slightly to the right. A slight enophthalmos was noted in his right eye. A computed tomography scan demonstrated entrapment of the medial rectus muscle and surrounding tissues in an old medial orbital wall fracture. A forced duction test revealed a marked restriction of abduction in the right eye. A 5 mm recession of the right medial rectus muscle was performed. Postoperatively, the patient's head turn and esotropia in the primary position were successfully corrected, but there was still some limitations to his ocular movement. The importance of several tests such as the forced duction test and an imaging study should be emphasized in making a diagnosis for limitation of eye movement.
Topics: Adolescent; Diagnosis, Differential; Duane Retraction Syndrome; Eye Movements; Follow-Up Studies; Humans; Male; Oculomotor Muscles; Ophthalmologic Surgical Procedures; Orbital Fractures; Tomography, X-Ray Computed
PubMed: 20046701
DOI: 10.3341/kjo.2009.23.4.329 -
Indian Journal of Ophthalmology 2007Duane's retraction syndrome (DRS) includes changes in palpebral fissure width along with restriction of ocular motility. Bardet Biedl syndrome (BBS) includes presence of...
Duane's retraction syndrome (DRS) includes changes in palpebral fissure width along with restriction of ocular motility. Bardet Biedl syndrome (BBS) includes presence of retinitis pigmentosa (RP) with obesity, mental retardation, polydactyly and renal abnormalities. We report a case of rare association of DRS with BBS in a seven-year-old child. The ocular motility examination revealed left DRS with esotropia. Fundus examination revealed findings characteristic of an atypical retinitis pigmentosa. The electro-retinogram waveforms were extinguished both for rods and cones. He was diagnosed as a case of BBS on the basis of the ophthalmological findings plus association with the systemic features of obesity, polydactyly, hypogonadism, mental retardation and renal abnormalities. This case gives further evidence of the fact that BBS may be associated with abnormalities of eye movements.
Topics: Bardet-Biedl Syndrome; Child; Diagnosis, Differential; Duane Retraction Syndrome; Electroretinography; Eye Movements; Humans; Male; Ophthalmoscopy; Visual Fields
PubMed: 17322606
DOI: 10.4103/0301-4738.30710 -
Seminars in Ophthalmology 2013In recent years, our understanding of the genetic foundations of incomitant strabismus has grown significantly. Much new understanding has been gleaned since the concept... (Review)
Review
In recent years, our understanding of the genetic foundations of incomitant strabismus has grown significantly. Much new understanding has been gleaned since the concept of congenital cranial dysinnervation disorders (CCDDs) was introduced in 2002, and the genetic basis of CCDDs continues to be elucidated. In this review, we aim to provide an update of the genetic and clinical presentation of these disorders. Disorders reviewed include Duane syndrome (DS), HOXA1 and HOXB1 syndromes, Moebius syndrome, congenital fibrosis of the extraocular muscles (CFEOM), and horizontal gaze palsy with progressive scoliosis (HGPPS).
Topics: Duane Retraction Syndrome; Eye Diseases, Hereditary; Fibrosis; Homeodomain Proteins; Humans; Mobius Syndrome; Ophthalmoplegia; Ophthalmoplegia, Chronic Progressive External; Scoliosis; Strabismus; Transcription Factors
PubMed: 24138051
DOI: 10.3109/08820538.2013.825288 -
Indian Journal of Ophthalmology Feb 2019Faden operation was first described in 1912. It weakens the muscle in its field of action without much slackening and alteration in the primary position. When combined...
Faden operation was first described in 1912. It weakens the muscle in its field of action without much slackening and alteration in the primary position. When combined with recession the weakening effect is more. It is a useful surgery in esotropia with high accommodative convergence, nystagmus blockage syndrome, dissociated vertical deviation, Duane's retraction syndrome with up or downshoots, and in sixth nerve paresis, where it is performed on the contralateral normal yoke muscle to increase the field of binocular vision. The conventional procedure is cumbersome due to small working space, entanglement of sutures, and posterior location of Faden site which is not easily accessible. We have modified the Faden operation by using a single 5-0 double-armed polyester suture, which is much easier and simpler to perform, and have done it in a series of small angle esotropias combined with recession. This paper demonstrates the surgical technique so that this surgery can be performed with ease by more surgeons.
Topics: Accommodation, Ocular; Adolescent; Child; Child, Preschool; Esotropia; Female; Humans; Male; Oculomotor Muscles; Ophthalmologic Surgical Procedures; Retrospective Studies; Suture Techniques; Sutures; Treatment Outcome; Vision, Binocular; Young Adult
PubMed: 30672484
DOI: 10.4103/ijo.IJO_952_18 -
Binocular Vision & Strabology... 2012Two siblings diagnosed with Okihiro Syndrome (also named Duane Radial Ray Syndrome) associated with ophthalmic manifestation including Duane Syndrome and retinal nerve...
BACKGROUND AND PURPOSE
Two siblings diagnosed with Okihiro Syndrome (also named Duane Radial Ray Syndrome) associated with ophthalmic manifestation including Duane Syndrome and retinal nerve fiber layer (RNFL) hypoplasia were presented.
METHODS
The first patient (15-years old female) was diagnosed of Duane Syndrome presenting reduction of visual acuity and pale optic discs. She showed a diffuse decrease in the RNFL thickness, mainly in her left eye, retaining the typical RNFL morphology as double hump, demonstrated by OCT and scanning laser polarimetry. Neurophysiology evaluation found a decrease in visual evoked potentials and pattern electroretinogram amplitudes, and an increase of the latency of P100 component. The second patient (12 year-old female) presented with Duane malformation. Both patients underwent a complete ophthalmic evaluation with best corrected visual acuity, visual field examination, optical coherence tomography (OCT), scanning laser polarimetry, visual evoked potentials, pattern electroretinogram, and genetic study.
RESULTS
The neuro-ophthalmic evaluation showed a subclinical reduction of RNFL average thickness provided by OCT and an increase of P50 and N95 latency by pattern electroretinogram. RNFL average thickness presented a score reduction in both patients, without typical glaucomatous morphology.
CONCLUSIONS
Our analyses suggest that Okihiro Syndrome may affect retinal nerve fiber layer development and visual acuity.
Topics: Duane Retraction Syndrome; Evoked Potentials, Visual; Humans; Nerve Fibers; Retinal Ganglion Cells; Strabismus
PubMed: 23234485
DOI: No ID Found -
Taiwan Journal of Ophthalmology 2017To report the surgical effect in upshoot of Duane retraction syndrome (DRS) with corecession of horizontal rectus muscles with or without Y-splitting.
PURPOSE
To report the surgical effect in upshoot of Duane retraction syndrome (DRS) with corecession of horizontal rectus muscles with or without Y-splitting.
PATIENTS AND METHODS
A retrospective chart review of six patients of DRS received muscle surgeries for upshoot in adducted position was performed.
RESULTS
From 1994 to 2010, six Duane patients received muscle surgeries for upshoots of lesion eye in adduction. Their age of receiving surgery ranged from 5 to 41 years. Four of the patients were male, and five had their left eye involved. Three underwent recession of ipsilateral medial and lateral rectus (LR) muscles, and the other three also received Y-splitting of LR muscle when recession. One of the patients that received Y-splitting showed mild hypertropia at down gaze postoperatively, and another one had little improvement of exotropia at the primary position. All patients showed improvement of their upshoots and lid fissure narrowing in adduction as well as face turn.
CONCLUSION
Postoperative improvements in abnormal head posture and upshoots were achieved with corecession of horizontal muscles with or without Y-splitting. Although Y-splitting of the LR muscle is an effective surgery, it might cause undesired complications.
PubMed: 29018752
DOI: 10.4103/tjo.tjo_23_17 -
Indian Journal of Ophthalmology 1992This report is a case of a 4 year old male child who was admitted for meningitis. On clinical examination he was diagnosed as a case of oculo-suriculo-vertebral...
Ocular motility disturbances (Duane retraction syndrome and double elevator palsy) with congenital heart disease, a rare association with Goldenhar syndrome--a case report.
This report is a case of a 4 year old male child who was admitted for meningitis. On clinical examination he was diagnosed as a case of oculo-suriculo-vertebral dysplasia with congenital heart disease, i.e., tetralogy of Fallots besides his presenting picture of meningitis. During his ophthalmic checkup for the conspicuous presence of epibulbar dermoid, he was discovered to have upper lid coloboma, double elevator palsy, and Grade 1 Duane retraction syndrome in his right eye while the pathognomic feature, a dermolipoma, was present in the left eye. The oculo-auriculo-vertebral dysplasia, as described by Goldenhar, is a disease complex of structures developed from the Ist and IInd branchial arch. The important feature of this case is the bilateral involvement of the disease complex over and above the presence of ocular motility disorders--Duane retraction syndrome and double elevator palsy.
Topics: Child, Preschool; Coloboma; Cornea; Eye Neoplasms; Goldenhar Syndrome; Heart Defects, Congenital; Humans; Lipoma; Male; Ocular Motility Disorders
PubMed: 1452286
DOI: No ID Found -
The Journal of Biological Chemistry Dec 2010Carboxypeptidase A6 (CPA6) is an extracellular matrix-bound metallocarboxypeptidase (CP) that has been implicated in Duane syndrome, a neurodevelopmental disorder in...
Carboxypeptidase A6 (CPA6) is an extracellular matrix-bound metallocarboxypeptidase (CP) that has been implicated in Duane syndrome, a neurodevelopmental disorder in which the lateral rectus extraocular muscle is not properly innervated. Consistent with a role in Duane syndrome, CPA6 is expressed in a number of chondrocytic and nervous tissues during embryogenesis. To better characterize the enzymatic function and specificity of CPA6 and to compare this with other CPs, CPA6 was expressed in HEK293 cells and purified. Kinetic parameters were determined using a panel of synthetic carboxypeptidase substrates, indicating a preference of CPA6 for large hydrophobic C-terminal amino acids and only very weak activity toward small amino acids and histidine. A quantitative peptidomics approach using a mixture of peptides representative of the neuropeptidome allowed the characterization of CPA6 preferences at the P1 substrate position and suggested that small and acidic P1 residues significantly inhibit CPA6 cleavage. Finally, a comparison of available kinetic data for CPA enzymes shows a gradient of specificity across the subfamily, from the very restricted specificity of CPA2 to the very broad activity of CPA4. Structural data and modeling for all CPA/B subfamily members suggests the structural basis for the unique specificities observed for each member of the CPA/B subfamily of metallocarboxypeptidases.
Topics: Carboxypeptidases A; Duane Retraction Syndrome; HEK293 Cells; Humans; Kinetics; Models, Molecular; Peptides; Structure-Activity Relationship; Substrate Specificity
PubMed: 20855895
DOI: 10.1074/jbc.M110.158626