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ELife Aug 2018In historical attempts to treat morning sickness, use of the drug thalidomide led to the birth of thousands of children with severe birth defects. Despite their...
In historical attempts to treat morning sickness, use of the drug thalidomide led to the birth of thousands of children with severe birth defects. Despite their teratogenicity, thalidomide and related IMiD drugs are now a mainstay of cancer treatment; however, the molecular basis underlying the pleiotropic biology and characteristic birth defects remains unknown. Here we show that IMiDs disrupt a broad transcriptional network through induced degradation of several CH zinc finger transcription factors, including SALL4, a member of the -like family of developmental transcription factors. Strikingly, heterozygous loss of function mutations in result in a human developmental condition that phenocopies thalidomide-induced birth defects such as absence of thumbs, phocomelia, defects in ear and eye development, and congenital heart disease. We find that thalidomide induces degradation of SALL4 exclusively in humans, primates, and rabbits, but not in rodents or fish, providing a mechanistic link for the species-specific pathogenesis of thalidomide syndrome.
Topics: Abnormalities, Multiple; Adaptor Proteins, Signal Transducing; Amino Acid Sequence; CYS2-HIS2 Zinc Fingers; Duane Retraction Syndrome; Embryonic Stem Cells; HEK293 Cells; Heart Defects, Congenital; Heart Septal Defects, Atrial; Humans; Lower Extremity Deformities, Congenital; Peptide Hydrolases; Phenotype; Protein Binding; Proteolysis; Reproducibility of Results; Species Specificity; Substrate Specificity; Teratogens; Thalidomide; Transcription Factors; Ubiquitin-Protein Ligases; Upper Extremity Deformities, Congenital
PubMed: 30067223
DOI: 10.7554/eLife.38430 -
Journal of Current Ophthalmology Dec 2017Surgical treatment in Duane retraction syndrome (DRS) can be very challenging even for the strabismus specialists because of a wide spectrum of diversity in clinical... (Review)
Review
PURPOSE
Surgical treatment in Duane retraction syndrome (DRS) can be very challenging even for the strabismus specialists because of a wide spectrum of diversity in clinical manifestations. The purpose of this article is to review these different surgical treatments.
METHODS
A comprehensive search was performed using PubMed database with the different keywords of "Duane retraction syndrome" and "surgery". Articles were selected from original English papers published since 2000. The full text of the selected articles was reviewed, and some articles were added based upon the references of the initial articles. We also provided selected case examples about some of these procedures.
RESULTS
125 articles were found in the initial search of which 37 articles were mostly related to the topic of this review. The number finally increased to 59 articles after considering the relative references of the initial articles. Different surgical methods performed on horizontal and vertical rectus muscles (recession, resection, transposition, Y splitting, periosteal fixation and posterior fixation suture) are reviewed. Careful selection of the surgical technique is important to achieve optimal results.
CONCLUSION
With accurate diagnosis of patients with DRS and proper surgical management, several adverse situations associated with this syndrome (amblyopia, abnormal head posture, upshoot, downshoot, and muscle underaction) can be prevented.
PubMed: 29270470
DOI: 10.1016/j.joco.2017.08.008 -
Clinical Ophthalmology (Auckland, N.Z.) 2017Duane retraction syndrome (DRS) is a congenital eye movement anomaly characterized by variable horizontal duction deficits, with narrowing of the palpebral fissure and... (Review)
Review
Duane retraction syndrome (DRS) is a congenital eye movement anomaly characterized by variable horizontal duction deficits, with narrowing of the palpebral fissure and globe retraction on attempted adduction, occasionally accompanied by upshoot or down-shoot. The etiopathogenesis of this condition can be explained by a spectrum of mechanical, innervational, neurologic and genetic abnormalities occurring independently or which influence each other giving rise to patterns of clinical presentations along with a complex set of ocular and systemic anomalies. Huber type I DRS is the most common form of DRS with an earlier presentation, while Huber type II is the least common presentation. Usually, patients with unilateral type I Duane syndrome have esotropia more frequently than exotropia, those with type II have exotropia and those with type III have esotropia and exotropia occurring equally common. Cases of bilateral DRS may have variable presentation depending upon the type of presentation in each eye. As regards its management, DRS classification based on primary position deviation as esotropic, exotropic or orthotropic is more relevant than Huber's classification before planning surgery. Surgical approach to these patients is challenging and must be individualized based on the amount of ocular deviation, abnormal head position, associated globe retraction and overshoots.
PubMed: 29133973
DOI: 10.2147/OPTH.S127481 -
International Journal of Ophthalmology 2020To study the different treatment modalities needed in cases of Duane's Retraction Syndrome (DRS).
AIM
To study the different treatment modalities needed in cases of Duane's Retraction Syndrome (DRS).
METHODS
This prospective study undergone in more than four years, in Alexandria, included 238 patients of DRS, including type I, 162 patients (68%), type II 12 patients (5%) and type III 64 patients (27%). Surgery was indicated in 98 (41%) of them, to eliminate abnormal head posture, deviation of the eye in primary position, severe retraction of the globe or cosmetically unacceptable upshoot with attempted adduction.
RESULTS
Type I was the most common and type II was the least. Females were predominant in this study, constituting 125 patients (52.5%), and males 113 patients (47.5%). Left eye was more affected, in 110 patients (46.2%), right eye in 91 patients (38.2%) and bilateral in 37 patients (15.6%). Amblyopia was found in 27 patients (11.3%) and treated in 13 patients under 10 years of age, by patching the normal eye. Ninety-eight patients (41%) were operated, the results were most satisfactory and a nomogram is followed in the surgical plan.
CONCLUSION
The surgical management is needed in less than half of the cases and should be planned for every case individually according to the clinical findings, planned nomogram and modified intraoperatively according to the anatomical findings during surgery.
PubMed: 32090038
DOI: 10.18240/ijo.2020.02.12 -
Taiwan Journal of Ophthalmology 2017Duane syndrome (DS) is a common form of congenital cranial dysinnervation disorders. The ocular motility pattern lies in a wide clinical spectrum, and the choice of... (Review)
Review
Duane syndrome (DS) is a common form of congenital cranial dysinnervation disorders. The ocular motility pattern lies in a wide clinical spectrum, and the choice of treatment must be individualized depending on the severity of the clinical findings. There is no perfect method of treatment and no real "cure" in DS. In this paper, the aim is to give some guidelines to the reader for selection of the most appropriate treatment method for the patient.
PubMed: 29018747
DOI: 10.4103/tjo.tjo_20_17 -
Indian Journal of Ophthalmology Jan 2019Duane retraction (or co-contraction) syndrome is a congenital restrictive strabismus which can occur either as an isolated entity or in conjunction with other congenital... (Review)
Review
Duane retraction (or co-contraction) syndrome is a congenital restrictive strabismus which can occur either as an isolated entity or in conjunction with other congenital anomalies and is now listed as a congenital cranial dysinnervation disorder. It is characterized by co-contraction of horizontal recti on attempted adduction causing globe retraction along with variable amounts of upshoots or downshoots. It may have limited abduction or adduction or both and present as esotropic, exotropic, or orthotropic Duane. The diagnosis of this disease is usually clinical. However, recent research has provided a greater insight into the genetic basis of this disease paving a way for a greater role of genetics in the diagnosis and management. This disease can have a varied presentation and hence the treatment plan should be tailor-made for every patient. The indications for surgery are abnormal head posture, deviations in the primary position, retraction and narrowing of palpebral aperture and up- or downshoots during adduction, and sometimes also to improve abduction. The arrival of newer surgical techniques of periosteal fixation (PF) of lateral rectus (LR), partial vertical rectus transposition, or superior or inferior rectus transposition in addition to LR recession with Y-split has vastly improved the management outcomes, providing not only primary position orthophoria but also increased binocular visual fields as well.
Topics: Disease Management; Duane Retraction Syndrome; Eye Movements; Humans; Oculomotor Muscles; Ophthalmologic Surgical Procedures; Vision, Binocular; Visual Fields
PubMed: 30574884
DOI: 10.4103/ijo.IJO_967_18 -
Beyoglu Eye Journal 2019Duane retraction syndrome (DRS) is a congenital syndrome characterized by limitation in adduction and/or abduction eye movements and narrowing of the palpebral fissure...
OBJECTIVES
Duane retraction syndrome (DRS) is a congenital syndrome characterized by limitation in adduction and/or abduction eye movements and narrowing of the palpebral fissure in adduction, and may include globe retraction, upshoot or downshoot. Several systemic abnormalities, syndromes, and additional ocular findings can accompany DRS. This study is an evaluation of eye findings in patients with DRS.
METHODS
The records of 632 patients with DRS who were followed up between 1995 and 2016 were reviewed retrospectively. Patients with a follow-up of less than 6 months and patients with a history of eye/cranial trauma or injury were not included in the study. Before the patients were examined, a detailed anamnesis was obtained. Details of the medical records, including additional systemic diseases, were recorded.
RESULTS
The average of follow-up time was 45 months (min-max: 6-128 months). There were 255 male and 377 female patients. A total of 34 patients (5.4%) had additional ocular abnormalities. The most frequently observed ocular pathologies associated with DRS were congenital ptosis (n=6, 0.94%) and coloboma of the iris (n=4, 0.63%).
CONCLUSION
Most cases of DRS are observed as isolated. However, various ocular and systemic abnormalities and syndromes are associated with DRS. In particular, synkinetic syndromes may frequently be seen alongside DRS. Therefore, a complete ocular examination and anamnesis are crucial in cases with DRS.
PubMed: 35187428
DOI: 10.14744/bej.2019.36854