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Scientific Reports Aug 2019Thalidomide is widely used for several diseases; however, it causes malformations in embryos exposed during pregnancy. The complete understanding of the mechanisms by...
Thalidomide is widely used for several diseases; however, it causes malformations in embryos exposed during pregnancy. The complete understanding of the mechanisms by which thalidomide affects the embryo development has not yet been obtained. The phenotypic similarity makes TE a phenocopy of syndromes caused by mutations in ESCO2, SALL4 and TBX5 genes. Recently, SALL4 and TBX5 were demonstrated to be thalidomide targets. To understand if these genes act in the TE development, we sequenced them in 27 individuals with TE; we verified how thalidomide affect them in human pluripotent stem cells (hPSCs) through a differential gene expression (DGE) analysis from GSE63935; and we evaluated how these genes are functionally related through an interaction network analysis. We identified 8 variants in ESCO2, 15 in SALL4 and 15 in TBX5. We compared allelic frequencies with data from ExAC, 1000 Genomes and ABraOM databases; eight variants were significantly different (p < 0.05). Eleven variants in SALL4 and TBX5 were previously associated with cardiac diseases or malformations; however, in TE sample there was no association. Variant effect prediction tools showed 97% of the variants with potential to influence in these genes regulation. DGE analysis showed a significant reduction of ESCO2 in hPSCs after thalidomide exposure.
Topics: Abnormalities, Multiple; Acetyltransferases; Brazil; Cell Line; Chromosomal Proteins, Non-Histone; Craniofacial Abnormalities; Datasets as Topic; Duane Retraction Syndrome; Ectromelia; Female; Gene Expression Profiling; Gene Frequency; Genetic Predisposition to Disease; Heart Defects, Congenital; Heart Septal Defects, Atrial; Humans; Hypertelorism; Leprosy; Lower Extremity Deformities, Congenital; Male; Mutation; Pluripotent Stem Cells; Polymorphism, Single Nucleotide; Pregnancy; Pregnancy Complications; Protein Interaction Maps; T-Box Domain Proteins; Teratogenesis; Thalidomide; Transcription Factors; Upper Extremity Deformities, Congenital
PubMed: 31388035
DOI: 10.1038/s41598-019-47739-8 -
Middle East African Journal of... 2019Marcus Gunn jaw-winking syndrome (MGJWS) is a rare form of congenital blepharoptosis and one of the congenital cranial dysinnervation disorders (CCDD). In addition,...
Marcus Gunn jaw-winking syndrome (MGJWS) is a rare form of congenital blepharoptosis and one of the congenital cranial dysinnervation disorders (CCDD). In addition, morning glory disc anomaly (MGDA) is a congenital optic disc anomaly of unknown etiology. The present report is the first to describe an association between MGJWS and MGDA in an otherwise healthy 7-year-old boy. He also had counting finger vision, anisometropia, esotropia, and monocular elevation deficiency in the same eye. In the literature, both MGJWS and MGDA have been reported to be associated with Duane retraction syndrome, a form of CCDD.
Topics: Anisometropia; Blepharoptosis; Child; Esotropia; Eye Abnormalities; Heart Defects, Congenital; Humans; Jaw Abnormalities; Male; Nervous System Diseases; Optic Disk; Reflex, Abnormal
PubMed: 31114123
DOI: 10.4103/meajo.MEAJO_279_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 -
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 -
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 -
Medicine Sep 2018Blepharoptosis (ptosis) is a common but often overlooked sign that may serve as a sign/manifestation of other conditions, ranging from a mild and purely cosmetic... (Review)
Review
Blepharoptosis (ptosis) is a common but often overlooked sign that may serve as a sign/manifestation of other conditions, ranging from a mild and purely cosmetic presentation to a severe and occasionally progressive disorder. Ptosis may show an acute onset or may manifest as a chronic disorder. Its presentation may vary: unilateral versus bilateral, progressive versus non-progressive, isolated versus complex which occurs in association with other symptoms, and congenital versus acquired (often concomitant with neuromuscular disorders).Congenital ptosis includes the isolated type-the congenital cranial dysinnervation disorders, which are further, distinguished into different subtypes such as Horner syndrome (HS), and ptosis as a sign/manifestation of various congenital malformation syndromes.In this article, we review the primary causes of ptosis occurring in childhood, and its various clinical presentations, including a short report on selected cases observed in our institution: a classical isolated familial ptosis comprising 14 members over 5 generations, 3 sibling with isolated congenital ptosis who in addition suffered by episodes of febrile seizures, a patient with Duane retraction syndrome who presented congenital skin and hair anomalies, and a girl with HS who showed a history of congenital imperforate hymen. A flowchart outlining the congenital and acquired type of ptosis and the clinical approach to the management and treatment of children with this anomaly is reported.
Topics: Blepharoptosis; Child; Child, Preschool; Diagnosis, Differential; Female; Humans; Male
PubMed: 30200099
DOI: 10.1097/MD.0000000000012124 -
Cell Reports Aug 2018Cranial motor nuclei in the brainstem innervate diverse types of head and neck muscles. Failure in establishing these neuromuscular connections causes congenital...
Cranial motor nuclei in the brainstem innervate diverse types of head and neck muscles. Failure in establishing these neuromuscular connections causes congenital cranial dysinnervation disorders (CCDDs) characterized by abnormal craniofacial movements. However, mechanisms that link cranial motor nuclei to target muscles are poorly understood at the molecular level. Here, we report that protocadherin-mediated repulsion mediates neuromuscular connection in the ocular motor system in zebrafish. We identify pools of abducens motor neurons that are topographically arranged according to soma size and convergently innervate a single muscle. Disruptions of Duane retraction syndrome-associated transcription factors reveal that these neurons require Mafba/MAFB, but not Sall4/SALL4, for differentiation. Furthermore, genetic perturbations of Pcdh17/protocadherin-17 result in defective axon growth and soma clumping, thereby abolishing neuromuscular connectivity. Our results suggest that protocadherin-mediated repulsion forms the central topography and efferent projection pattern of the abducens nucleus following Mafba-dependent specification and imply potential involvement of protocadherins in CCDD etiology.
Topics: Abducens Nucleus; Animals; Brain Stem; Humans; Zebrafish
PubMed: 30089266
DOI: 10.1016/j.celrep.2018.07.024 -
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 -
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 -
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