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American Journal of Human Genetics Nov 2002Duane syndrome is a congenital eye movement disorder characterized most typically by absence of abduction, restricted adduction, and retraction of the globe on attempted...
Duane syndrome is a congenital eye movement disorder characterized most typically by absence of abduction, restricted adduction, and retraction of the globe on attempted adduction. Duane syndrome can be coinherited with radial ray anomalies as an autosomal dominant trait, referred to as "Okihiro syndrome" or "Duane radial ray syndrome" (DRRS). We ascertained three pedigrees with DRRS and mapped their disease gene to a 21.6-cM region of chromosome 20 flanked by markers D20S888 and D20S102. A new member of the SAL family of proposed C(2)H(2) zinc finger transcription factors, SALL4, falls within the region. Mutation analysis of SALL4 in the three pedigrees revealed one nonsense and two frameshift heterozygous mutations. SALL4 represents the first identified Duane syndrome gene and the second malformation syndrome resulting from mutations in SAL genes and likely plays a critical role in abducens motoneuron development.
Topics: Chromosome Mapping; Chromosomes, Human, Pair 20; Duane Retraction Syndrome; Female; Humans; Lod Score; Male; Molecular Sequence Data; Mutation; Pedigree; Sequence Analysis, DNA; Sequence Analysis, Protein; Transcription Factors; Zinc Fingers
PubMed: 12395297
DOI: 10.1086/343821 -
Human Molecular Genetics Aug 2017Unraveling the genetics of the paralytic strabismus syndromes known as congenital cranial dysinnervation disorders (CCDDs) is both informing physicians and their... (Review)
Review
Unraveling the genetics of the paralytic strabismus syndromes known as congenital cranial dysinnervation disorders (CCDDs) is both informing physicians and their patients and broadening our understanding of development of the ocular motor system. Genetic mutations underlying ocular CCDDs alter either motor neuron specification or motor nerve development, and highlight the importance of modulations of cell signaling, cytoskeletal transport, and microtubule dynamics for axon growth and guidance. Here we review recent advances in our understanding of two CCDDs, congenital fibrosis of the extraocular muscles (CFEOM) and Duane retraction syndrome (DRS), and discuss what they have taught us about mechanisms of axon guidance and selective vulnerability. CFEOM presents with congenital ptosis and restricted eye movements, and can be caused by heterozygous missense mutations in the kinesin motor protein KIF21A or in the β-tubulin isotypes TUBB3 or TUBB2B. CFEOM-causing mutations in these genes alter protein function and result in axon growth and guidance defects. DRS presents with inability to abduct one or both eyes. It can be caused by decreased function of several transcription factors critical for abducens motor neuron identity, including MAFB, or by heterozygous missense mutations in CHN1, which encodes α2-chimaerin, a Rac-GAP GTPase that affects cytoskeletal dynamics. Examination of the orbital innervation in mice lacking Mafb has established that the stereotypical misinnervation of the lateral rectus by fibers of the oculomotor nerve in DRS is secondary to absence of the abducens nerve. Studies of a CHN1 mouse model have begun to elucidate mechanisms of selective vulnerability in the nervous system.
Topics: Animals; Axons; Congenital Abnormalities; Duane Retraction Syndrome; Eye Diseases, Hereditary; Fibrosis; Humans; Kinesins; Mice; Mutation; Mutation, Missense; Ocular Motility Disorders; Oculomotor Muscles; Ophthalmoplegia; Skull; Tubulin
PubMed: 28459979
DOI: 10.1093/hmg/ddx168 -
Journal of Pediatric Genetics Sep 2012The chromosome 9p deletion syndrome is a rare but specific clinical event. The clinical manifestations include dysmorphic facial features (trigonocephaly, midface...
The chromosome 9p deletion syndrome is a rare but specific clinical event. The clinical manifestations include dysmorphic facial features (trigonocephaly, midface hypoplasia, upward slanting palpebral fissures, and a long philtrum) and psychomotor retardation. Here we report a child with chromosome 9p deletion with Duane retraction syndrome, which has never been reported in the literature before.
PubMed: 27625822
DOI: 10.3233/PGE-2012-030 -
Molecular Medicine Reports Apr 2022Okihiro syndrome is an autosomal dominant condition characterized by Duane anomaly and radial ray defects. The present study aimed to analyze the clinical manifestations...
Okihiro syndrome is an autosomal dominant condition characterized by Duane anomaly and radial ray defects. The present study aimed to analyze the clinical manifestations of a patient with Okihiro syndrome and perform genetic testing on the proband and his family to determine the biological pathogenesis. Clinical data were collected from the proband and his family and genomic DNA was extracted from peripheral blood. Whole exome sequencing was performed by high‑throughput sequencing and mutation sites of the proband and his parents were validated by Sanger sequencing. The proband was diagnosed with Okihiro syndrome, which is characterized by bone abnormality in the arms and hands (radial ray malformation, absence of thumbs) and sensorineural hearing loss. A pathogenic heterozygous c.3060delG variant was identified in exon 4 of spalt‑like transcription factor 4 () gene in the proband. This is a frameshift mutation that changes increases the length of SALL4 protein from 1,053 to 1,076 amino acids. The variant was classed as a mutation because the parents of the proband showed no variation at this site. This variant is not included in the ClinVar database and, to the best of our knowledge, has not previously been reported. The heterozygous c.3060delG variant was the molecular pathological cause of Okihiro syndrome in the present study and expanded the database of known variants.
Topics: China; Duane Retraction Syndrome; Heterozygote; Humans; Mutation; Pedigree; Transcription Factors
PubMed: 35179219
DOI: 10.3892/mmr.2022.12647 -
American Journal of Ophthalmology Nov 2006To help resolve the clinical ambiguity between Duane syndrome with severe abduction deficit and abducens palsy, we performed orbital magnetic resonance imaging (MRI) to... (Comparative Study)
Comparative Study
PURPOSE
To help resolve the clinical ambiguity between Duane syndrome with severe abduction deficit and abducens palsy, we performed orbital magnetic resonance imaging (MRI) to qualify abnormalities of the lateral rectus (LR) muscle in these entities.
DESIGN
Prospective observational case series.
METHODS
Orbital MRI was performed in 13 subjects with Duane syndrome (19 eyes), 10 subjects with chronic abducens palsy (10 eyes), and 10 orthotropic control subjects (18 eyes). High-resolution, surface coil, T(1)-weighted MRI was used to obtain contiguous, 2-mm thick quasi-coronal images of the orbits in central gaze. Digital image analysis was used to quantify cross-sectional area of the ipsilesional and contralesional LR to provide comparison with control measurements.
RESULTS
Mean maximum LR cross-sectional area in Duane syndrome was statistically similar to control (P = .454) and contralesional LR cross-sectional area (P = .227). However, in chronic abducens palsy, mean maximum ipsilesional LR cross-sectional area was markedly smaller than contralesional (P = .003) and control cross-sectional areas (P < .0001), as well as smaller than the LR in Duane syndrome (P= .0017).
CONCLUSIONS
The LR muscle in abducens palsy exhibits profound atrophy. The sparing of the LR in Duane syndrome from denervation atrophy despite absence of normal abducens innervation suggests existence of alternative LR innervation. High-resolution MRI can noninvasively demonstrate LR muscle size and distinguish Duane syndrome from chronic abducens palsy in uncertain cases.
Topics: Abducens Nerve Diseases; Adolescent; Adult; Aged; Atrophy; Child; Child, Preschool; Chronic Disease; Duane Retraction Syndrome; Esotropia; Eye Movements; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Oculomotor Muscles; Orbit; Prospective Studies
PubMed: 16989758
DOI: 10.1016/j.ajo.2006.06.012 -
Science (New York, N.Y.) Aug 2008Duane's retraction syndrome (DRS) is a complex congenital eye movement disorder caused by aberrant innervation of the extraocular muscles by axons of brainstem motor...
Duane's retraction syndrome (DRS) is a complex congenital eye movement disorder caused by aberrant innervation of the extraocular muscles by axons of brainstem motor neurons. Studying families with a variant form of the disorder (DURS2-DRS), we have identified causative heterozygous missense mutations in CHN1, a gene on chromosome 2q31 that encodes alpha2-chimaerin, a Rac guanosine triphosphatase-activating protein (RacGAP) signaling protein previously implicated in the pathfinding of corticospinal axons in mice. We found that these are gain-of-function mutations that increase alpha2-chimaerin RacGAP activity in vitro. Several of the mutations appeared to enhance alpha2-chimaerin translocation to the cell membrane or enhance its ability to self-associate. Expression of mutant alpha2-chimaerin constructs in chick embryos resulted in failure of oculomotor axons to innervate their target extraocular muscles. We conclude that alpha2-chimaerin has a critical developmental function in ocular motor axon pathfinding.
Topics: Abducens Nerve; Amino Acid Sequence; Animals; Axons; Cell Line; Cell Membrane; Chick Embryo; Chimerin 1; Duane Retraction Syndrome; Female; Gene Expression Profiling; Heterozygote; Humans; Male; Molecular Sequence Data; Mutation, Missense; Oculomotor Muscles; Oculomotor Nerve; Pedigree
PubMed: 18653847
DOI: 10.1126/science.1156121 -
Neurology India 2022Cerebral venous sinus thrombosis (CVST) is a life-threatening condition with a predilection for a younger age group. Patients with CVST can have features of raised...
BACKGROUND
Cerebral venous sinus thrombosis (CVST) is a life-threatening condition with a predilection for a younger age group. Patients with CVST can have features of raised intracranial pressure that can be suspected clinically based on ophthalmological findings such as bilateral abduction restriction, papilledema.
CASE DESCRIPTION
A 27-year-old gentleman presented with 15 days history of headache and seizures with complete abduction restriction of both eyes along with retraction of globe and narrowing of palpebral fissure on abduction. His MRI brain showed superior sagittal sinus thrombosis without any parenchymal lesion.
CONCLUSION
The final diagnosis in our case was bilateral inverse Duane's retraction syndrome with CVST, a co-occurrence that has not been reported in the past and can be missed if the eye movements are attributed to raised intracranial pressure alone.
Topics: Male; Humans; Adult; Duane Retraction Syndrome; Eye Movements; Magnetic Resonance Imaging; Neuroimaging; Sagittal Sinus Thrombosis; Sinus Thrombosis, Intracranial
PubMed: 36537432
DOI: 10.4103/0028-3886.364070 -
Eye (London, England) Mar 2014The aim of this study was to evaluate the motor, sensory, functional, and head posture results of recession of the lateral rectus muscle contralateral to the involved... (Observational Study)
Observational Study
AIMS
The aim of this study was to evaluate the motor, sensory, functional, and head posture results of recession of the lateral rectus muscle contralateral to the involved eye in patients with exotropic Duane retraction syndrome (DRS) type 3.
METHODS
This was a retrospective, longitudinal, observational study of a consecutive clinical case series. Of the 11 patients with DRS type 3 operated on at a tertiary medical center from 1977 to 2012, 8 underwent recession of the lateral rectus muscle contralateral to the involved eye (with combined Y-splitting of ipsilateral lateral rectus muscle in 3 of them). Full ophthalmic, orthoptic, and neurological examination was performed before and after surgery. Main outcome measures included intragroup changes in motor misalignment, abnormal head turn, ocular upshoot, and stereopsis.
RESULTS
Mean patient age was 8.75±3.1 years at surgery. Mean exodeviation for distance was -17.3±3.5 prism diopters (PD) preoperatively and -4.0±6.1 PD postoperatively; corresponding values for near were -23.1±7.2 PD and -5.9±8.7 PD. Motor deviation improved by 77% for distance (P=0.017) and 74.5% for near (P=0.01). In 7/8 patients, the postoperative residual exodeviation (distance and near) was <8.0 PD. There was an 80% improvement in head turn, from 15.3±4° before surgery to 3.1±5.0° after (P=0.01). Stereopsis improved significantly in 6/8 patients. Findings remained stable during follow-up (mean duration 35.9±50.8 months, range 5-132 months).
CONCLUSIONS
Contralateral lateral rectus muscle recession appears to be a promising technique for the treatment of moderate unilateral DRS type 3, with patients showing significant motor and functional improvement and a decrease in head turn.
Topics: Adolescent; Child; Child, Preschool; Depth Perception; Duane Retraction Syndrome; Exotropia; Female; Follow-Up Studies; Functional Laterality; Head; Humans; Male; Oculomotor Muscles; Ophthalmologic Surgical Procedures; Posture; Retrospective Studies; Young Adult
PubMed: 24310235
DOI: 10.1038/eye.2013.260 -
Isolated y-splitting and recession of the lateral rectus muscle in patients with exo-duane syndrome.Strabismus Sep 2012Weakening of both horizontal rectus muscles is performed for patients with Duane syndrome and significant misinnervation of the lateral rectus (LR) muscle resulting in... (Comparative Study)
Comparative Study
PURPOSE
Weakening of both horizontal rectus muscles is performed for patients with Duane syndrome and significant misinnervation of the lateral rectus (LR) muscle resulting in strabismus, limitation to ocular rotations, and globe retraction. In patients with severe up-/downshoots, a Y-splitting of the LR is often recommended. The purpose of this study was to evaluate the efficacy of isolated unilateral LR recession-Y splitting in exo-Duane patients with limitation to adduction and up-/downshoots.
METHODS
etrospective review of the records of consecutive patients with exo-Duane syndrome and up/down-shoots who underwent isolated Y-splitting-recession of the affected LR.
RESULTS
The records of 10 patients were reviewed (mean age at surgery 23 ± 21 years). The Y-split was performed 10 mm posterior to the insertion and was combined with a mean LR recession of 8.7 ± 2.9 mm. Torticollis decreased from 12.7 ± 4.4° to 4.8 ± 5.3° (P = 0.003). Exotropia improved from 18.4 ± 7.3 to 6.2 ± 5.9 PD postoperatively (P < 0.001). Exotropia in contralateral gaze improved from 33.7 ± 11.8 to 18.7 ± 18.1 PD postoperatively (P = 0.09). No significant postoperative changes in esotropia in ipsilateral gaze, vertical deviations, or ocular rotations in adduction or abduction were observed. Downshoots were significantly decreased (P = 0.01), and there was a trend toward improvement of upshoots (P = 0.07). There were no overcorrections, although 3 patients required additional LR weakening and transposition.
CONCLUSIONS
LR Y-splitting-recession improves ocular alignment, torticollis, and up-/downshoots. LR recession improves ocular alignment and torticollis, while the addition of a Y-split procedure improves up-/downshoots.
Topics: Adolescent; Adult; Aged; Child; Duane Retraction Syndrome; Esotropia; Female; Follow-Up Studies; Humans; Male; Middle Aged; Oculomotor Muscles; Ophthalmologic Surgical Procedures; Postoperative Period; Retrospective Studies; Treatment Outcome; Vision, Binocular; Young Adult
PubMed: 22906380
DOI: 10.3109/09273972.2012.702323 -
Clinical & Experimental Optometry Jan 2012The aim was to study the clinical characteristics of Duane's retraction syndrome (DRS) in Nepalese patients. (Comparative Study)
Comparative Study
PURPOSE
The aim was to study the clinical characteristics of Duane's retraction syndrome (DRS) in Nepalese patients.
METHOD
Medical records from 52 cases of DRS from May 2003 to April 2010 were retrospectively reviewed for age, gender, laterality and clinical characteristics. Forty-one case records (78.8 per cent) that had complete clinical findings were considered for further evaluation. Examination included visual acuity by Snellen chart, refraction, associated horizontal and vertical strabismus in primary gaze, upshoot and downshoot on attempted adduction, binocular vision assessed with the Worth four-dot test on adopted gaze and stereopsis examined with the Titmus stereo test.
RESULTS
DRS type I was the most common type observed in 73.2 per cent of cases, followed by DRS type II (14.6 per cent) and DRS type III (12.2 per cent). It was more common in female patients (58.5 per cent) than male patients (χ(2) = 4.6, df = 1, p = 0.03). DRS was more common in the left eye (68.3 per cent) than the right eye and unilaterally present in 95.1 per cent of subjects. In primary gaze, orthotropia (41.5 per cent) was more common than exotropia (34.1 per cent) and esotropia (24.4 per cent) and vertical strabismus was present in 24.4 per cent of subjects. Upshoot and downshoot on attempted adduction was seen in 14.6 and 9.8 per cent, respectively. Binocular single vision was present in 68.3 per cent of subjects by Worth four-dot test at near. Stereopsis of 3,000 seconds of arc was present in 9.8 per cent, 100 to 200 seconds of arc in 14.6 per cent and 40 to 60 seconds of arc in 43.9 per cent with the Titmus stereo test.
CONCLUSION
DRS is more common in female patients and the left eye. DRS type I is the most common type.
Topics: Adolescent; Adult; Age Distribution; Amblyopia; Child; Child, Preschool; Duane Retraction Syndrome; Eye Movements; Female; Follow-Up Studies; Humans; Male; Nepal; Prevalence; Prognosis; Refraction, Ocular; Retrospective Studies; Risk Factors; Sex Distribution; Strabismus; Vision, Binocular; Young Adult
PubMed: 21916997
DOI: 10.1111/j.1444-0938.2011.00635.x