DOCSLIB.ORG

Novel Anterior Segment Phenotypes Resulting from Forkhead Gene Alterations: Evidence for Cross-Species Conservation of Function

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Novel Anterior Segment Phenotypes Resulting from Forkhead Gene Alterations: Evidence for Cross-Species Conservation of Function Novel Anterior Segment Phenotypes Resulting from Forkhead Gene Alterations: Evidence for Cross-Species Conservation of Function Ordan J. Lehmann,1 Stephen Tuft,2 Glen Brice,3 Richard Smith,4 Åsa Blixt,5 Rachel Bell,3 Bengt Johansson,6 Tim Jordan,1 Roger A. Hitchings,2 Peng T. Khaw,2 Simon W. M. John,4 Peter Carlsson,5 and Shomi S. Bhattacharya1 PURPOSE. Mutations in murine and human versions of an ances- cause it may affect the clinical management of certain trally related gene usually result in similar phenotypes. How- glaucoma subtypes and lead to excessive treatment. The ever, interspecies differences exist, and in the case of two FOXC1 and Foxe3 data, taken together with the novel ocular forkhead transcription factor genes (FOXC1 and FOXC2), phenotypes of FOXC2 mutations, highlight the remarkable these differences include corneal or anterior segment pheno- cross-species conservation of function among forkhead genes. types, respectively. This study was undertaken to determine (Invest Ophthalmol Vis Sci. 2003;44:2627–2633) DOI:10.1167/ whether such discrepancies provide an opportunity for iden- iovs.02-0609 tifying novel human–murine ocular phenotypes. METHODS. Four pedigrees with early-onset glaucoma pheno- types secondary to segmental chromosomal duplications or ecognition that mutations in orthologous genes frequently deletions encompassing FOXC1 and 18 individuals from 9 Rcause similar phenotypes has allowed the field of compar- FOXC2 mutation pedigrees underwent detailed ocular pheno- ative genetics to contribute to the understanding of human typing. Subsequently, mice with mutations in Foxc1 or a re- disease. As the human, murine, and Drosophila PAX6 mutants lated forkhead gene, Foxe3, were assessed for features of the (aniridia, Small eye, and eyeless) demonstrate, genotypic con- human phenotypes. servation can be mirrored in a phenotype extending across a considerable evolutionary time span. The same phenomenon is RESULTS. A significant increase in central corneal thickness was exhibited by members of the Forkhead Box (Fox) transcription present in affected individuals from the segmental duplication factor gene family, as the thyroid, immunodeficiency, and pedigrees compared with their unaffected relatives (mean in- Ͻ scurfy-related phenotypes of Foxe1/FOXE1, Foxn1/FOXN1 crease 13%, maximum 35%, P 0.05). Alterations in corneal and Foxp3/FOXP3 mutants illustrate. Forkhead genes also ex- thickness were present in mice heterozygous and homozygous hibit common functional characteristics, including sensitivity for Foxe3 mutations but neither in Foxc1 heterozygotes nor to altered gene dosage—a feature that is conserved between the small human segmental deletion pedigree. Mutations in such evolutionarily divergent organisms as mammals and ze- FOXC2 resulted in ocular anterior segment anomalies. These brafish.1–4 Despite this close relationship, appreciable differ- were more severe and prevalent with mutations involving the ences exist between the reported ocular phenotypes of certain forkhead domain. human (FOXC1/FOXC2) and murine (Foxc1/Foxc2) forkhead CONCLUSIONS. Normal corneal development is dependent on the orthologues, which may be attributable to real biological dif- precise dose and levels of activity of certain forkhead transcrip- ferences, variations in genetic background, and/or aspects of tion factors. The altered corneal thickness attributable to in- the phenotypes that had not been assessed. creased forkhead gene dosage is particularly important, be- Mutations in the FOXC1 gene, located on chromosome 6p25, principally result in a range of Axenfeld-Rieger pheno- types that are strongly associated with glaucoma.5–7 The natu- 1 ral murine Foxc1 mutant, congenital hydrocephalus, in the From the Department of Molecular Genetics, Institute of Oph- ch/ch thalmology, London, United Kingdom; 2Moorfields Eye Hospital, Lon- homozygous state (Foxc1 ) dies in the perinatal period 8 don, United Kingdom; the 3Department of Medical Genetics, St. with cerebral, cardiac, ocular, renal, and skeletal defects. The George’s Hospital Medical School, London, United Kingdom; 4The ocular abnormalities include iris anomalies similar to those in Howard Hughes Medical Institute, The Jackson Laboratory, Bar Harbor, humans, and, in addition, profound corneal changes. These Maine; and the Departments of 5Molecular Biology and 6Anatomy and include failure of the corneal endothelium and lens epithelium Cell Biology, Go¨teborg University, Go¨teborg, Sweden. to separate, resulting in absence of anterior chamber forma- Supported in part by grants from Moorfields Eye Hospital Special tion.1,8 Milder corneal (iris and systemic) disease occurs in Trustees and the International Glaucoma Association (and Tadpoles ch/ϩ ϩ/Ϫ Association). OJL was supported by a fellowship from the Iris Fund. heterozygous (Foxc1 and knockout Foxc1 ) mutant mice demonstrating a relationship between the severity of the SWMJ is an Associate Investigator of the Howard Hughes Medical 2,9 Institute. phenotype and the dose of FOXC1. However, such corneal Submitted for publication June 19, 2002; revised August 21, 2002, phenotypes have not been a characteristic observation in ei- and January 7, 2003; accepted January 21, 2003. ther FOXC1 mutations or cytogenetic abnormalities that alter Disclosure: O.J. Lehmann, None; S. Tuft, None; G. Brice, None; FOXC1 gene dosage.8,10–12 Mutations in another forkhead R. Smith, None; Å. Blixt, None; R. Bell, None; B. Johansson, None; gene, Foxe3/FOXE3, cause a failure of corneolenticular sepa- T. Jordan, None; R.A. Hitchings, None; P.T. Khaw, None; S.W.M. ration similar to Foxc1ch/ch, resulting either in the (murine) John, None; P. Carlsson, None; S.S. Bhattacharya, None dysgenetic lens (dyl) phenotype or a proportion of (human) The publication costs of this article were defrayed in part by page 13–16 charge payment. This article must therefore be marked “advertise- Peters anomaly or anterior segment dysgenesis cases. The corneal phenotypes of Foxc1, Foxe3, and FOXE3 mutants plus ment” in accordance with 18 U.S.C. §1734 solely to indicate this fact. 8,17 Corresponding author: Ordan J. Lehmann, Department of Molec- the corneal expression of Foxc1/FOXC1, suggested the ular Genetics, Institute of Ophthalmology, Bath Street, London EC1V existence of an as yet unidentified role for FOXC1 in human 9EL, UK; [email protected]. corneal development. Investigative Ophthalmology & Visual Science, June 2003, Vol. 44, No. 6 Copyright © Association for Research in Vision and Ophthalmology 2627 Downloaded from tvst.arvojournals.org on 09/29/2021 2628 Lehmann et al. IOVS, June 2003, Vol. 44, No. 6 FOXC1 shares coordinated function and overlapping tissue Oberkochen, Germany]). Slit lamp biomicroscopy, pachymetry, and expression with FOXC2, as well as 97% amino acid identity specular microscopy of the cohort of patients with lymphedema- across their forkhead (DNA binding) domains.2–4 Mutations in distichiasis was performed by an ophthalmologist (OJL) masked to the FOXC2 cause an autosomal dominant disease characterized by presence or nature of any FOXC2 mutation. The iridocorneal angles, lymphedema of the limbs and distichiasis (additional diminu- assessed by gonioscopy, were graded as either normal or abnormal, tive eyelashes).18 In contrast, haploinsufficiency of Foxc2 in and abnormalities of the iris, cornea, and optic nerve were docu- knockout (Foxc2ϩ/Ϫ) mice causes iris, trabecular meshwork, mented with a digital slit lamp–mounted camera (DXC-950P; Sony and iridocorneal angle anomalies.2 The presence of murine Corp., Tokyo, Japan). This study adhered to the tenets of the Declara- anterior segment anomalies raises the possibility of an unrec- tion of Helsinki and to the ARVO Statement for the Use of Animals in ognized role for FOXC2 in iris and trabecular meshwork de- Ophthalmic and Vision Research. velopment (analogous to that of FOXC1 in corneal develop- ment). The close functional and phenotypic relationship between RESULTS forkhead orthologues suggests that scrutiny of differences be- tween the phenotypes caused by mutations in Foxc1/FOXC1 CCT was increased in affected individuals (mean 600 ␮m, n ϭ and Foxc2/FOXC2 may provide a model for determining un- 27) from each of the three segmental duplication pedigrees recognized phenotypes. The results from a detailed ocular compared with their unaffected relatives (A, B, and C: P ϭ assessment of patients or model organisms with altered FOXC1 0.008, 0.044, and 0.003, respectively; Fig. 1). Elevated CCT was gene dosage or FOXC2 mutations illustrate how this simple present in affected individuals who had neither had glaucoma approach can elucidate aspects of gene function and have nor required glaucoma surgery. Specular microscopy in an implications for the management of certain developmental unselected subset of affected individuals (34/54 eyes) revealed glaucomas. normal corneal endothelial cell morphology and density (Ͼ2500 cells/mm2) (Fig. 2). CCT measurements from unaf- ␮ ϭ METHODS fected individuals (pedigrees A–C; mean, 532 m; n 20), patients with segmental 6p25 deletion (pedigree D; mean, 540 Four pedigrees (A–D) with 6p25 segmental duplications or deletions ␮m; n ϭ 3), and control individuals with unaffected or glau- encompassing FOXC1 have been identified by microsatellite marker comatous eyes were very similar (Fig. 1) and closely matched genotyping or fluorescence in situ hybridization (FISH)11,12 (Lehmann the published values for individuals in the United Kingdom.21 ϩ Ϫ OJ, Jordan TL, Ebenezer N, et
Load more

Recommended publications
  • Treatment of Congenital Ptosis
    13 Review Article Page 1 of 13 Treatment of congenital ptosis Vladimir Kratky1,2^ 1Department of Ophthalmology, Queen’s University, Kingston, Canada; 21st Medical Faculty, Charles University, Prague, Czech Republic Correspondence to: Vladimir Kratky, BSc, MD, FRCSC, DABO. Associate Professor of Ophthalmology, Director of Ophthalmic Plastic and Orbital Surgery, Oculoplastics Fellowship Director, Queen’s University, Kingston, Canada; 1st Medical Faculty, Charles University, Prague, Czech Republic. Email: [email protected]. Abstract: Congenital ptosis is an abnormally low position of the upper eyelid, with respect to the visual axis in the primary gaze. It can be present at birth or manifest itself during the first year of life and can be bilateral or unilateral. Additionally, it may be an isolated finding or part of a constellation of signs of a specific syndrome or systemic associations. Depending on how much it interferes with the visual axis, it may be considered as a functional or a cosmetic condition. In childhood, functional ptosis can lead to deprivation amblyopia and astigmatism and needs to be treated. However, even mild ptosis with normal vision can lead to psychosocial problems and correction is also advised, albeit on a less urgent basis. Although, patching and glasses can be prescribed to treat the amblyopia, the mainstay of management is surgical. There are several types of surgical procedure available depending on the severity and etiology of the droopy eyelid. The first part of this paper will review the different categories of congenital ptosis, including more common associated syndromes. The latter part will briefly cover the different surgical approaches, with emphasis on how to choose the correct condition.
    [Show full text]
  • Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome
    Blepharophimosis, ptosis, and epicanthus inversus syndrome Case Report A rare case of adult-onset blepharophimosis, ptosis, and epicanthus inversus syndrome: Case report Mahesha S1, Shruthi Bhimalli2, Manoj Y Bhat2 From 1Chief Medical Officer, 2Fellow in IOL, Department of Cataract and Trauma, Sankara Eye Hospital, Harakere, Shimoga, Karnataka, India Correspondence to: Dr. Shruthi Bhimalli, Department of Cataract and Trauma, Sankara Eye Hospital, Harakere, Shimoga - 577202, Karnataka, India. E-mail: [email protected] Received - 02 June 2019 Initial Review - 24 June 2019 Accepted - 25 July 2019 ABSTRACT Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) is a rare genetic condition caused by a mutation in the FOXL2 gene and it is inherited in an autosomal dominant pattern. Identification and diagnosis of BPES syndrome by an ophthalmologist are relatively easy, based on the characteristic ocular manifestations. The most common age group at the time of diagnosis is 4 to 8 years. Here, we present an unusual case of BPES in a patient who presented with the syndrome at the age of 52 years. There is a need for increased awareness about this condition among ophthalmologists as early diagnosis is the key factor in preventing long term complications. Keywords: Blepharophimosis, Epicanthus inversus syndrome, Ptosis. lepharophimosis, ptosis, and epicanthus inversus action, epicanthus inversus and telecanthus (Fig. 1). On acuity syndrome (BPES) is a genetic condition associated testing, his best vision was ‘finger counting close to face’ in his Bwith mutations in the Fork head Box L2 (FOXL2) gene. right eye and ‘finger counting at one meter’ in his left eye. He had The syndrome is inherited in an autosomal dominant pattern, with corneal ectasia with scarring and vascularization (Fig.
    [Show full text]
  • P> Resident’S Day Submission Kelsie Morrison, OD Pediatric Optometry Resident University of Houston College of Optometry
    Resident’s Day Submission Kelsie Morrison, OD Pediatric Optometry Resident University of Houston College of Optometry Title: Presumed Blepharophimosis Ptosis Epicanthus Inversus Syndrome (BPES) with Bilateral Type I Duane’s Retraction Syndrome Abstract: Blepharophimosis, ptosis, epicanthus inversus syndrome (BPES) is a rare congenital autosomal dominant condition characterized by bilateral ptosis, telecanthus, epicanthus inversus, and blepharphimosis. The following case highlights the management of ocular manifestations associated with BPES. I. Case History Patient demographics: 7 year old half Caucasian, half Asian male Chief complaint: Annual strabismus evaluation o The patient’s father reported good vision without glasses and non-compliance with spectacle wear. Ocular history: o (+) Bilateral Duane’s retraction syndrome type I o (+) Constant left esotropia with possible strabmismic amblyopia o (+) Telecanthus o (+) Epicanthal folds Medical history: o (+) Unbalanced translocation genetic mutation involving chromosomes 3 and 7 o (+) Developmental delays Systemic surgical history: o (+) Open heart surgery at 1 month old o (+) G-tube at 2 months old o (+) Hand surgery at 1 year old and 1.5 years old o (+) Current G-tube fed secondary to previous ‘failure to thrive’ diagnosis Medications o (+) Hydrocortisone cream o (+) Murolax o No known systemic or ocular medication allergies Family medical and ocular history: o No known family members with chromosomal anomalies Social history: o Attends a special needs school where he is in the
    [Show full text]
  • Distichiasis (Distichia)
    DISTICHIASIS (DISTICHIA) What is distichiasis? Distichiasis is a common condition that affects dogs, and less commonly, cats. The normal eyelid margin is devoid of hairs. There are multiple glands (called meibomian glands) along the eyelids which produce an oily secretion. Occasionally a hair can arise from or near these glands and project out of the eyelid. This hair is called a distichium, and the plural is distichia. These hairs may or may not come in contact with the cornea. This depends on whether they are thick/stiff or fine, and in which direction they are growing (they may be directed inwards). What problems do they cause? Some distichia do not cause any problems. These are usually fine hairs, or hairs which are directed away from the cornea. Problems arise when the hairs rub on the cornea. It causes discomfort, and the animal may have a watery eye discharge and have excessive blinking. The hair can rub on the cornea and abrade it, causing a corneal ulcer. These corneal ulcers are very difficult to treat, as the hair continues to rub in the same area, preventing healing. Distichia grow in young dogs, and if they are going to cause a problem, they usually do so ion dogs of less than two years of age. However, occasionally they can become problematic in later life, particularly if the dog gets a condition called Dry Eye or keratoconjunctivitis sicca. In this condition, there is a deficiency in tears, making the eyes dry and more susceptible to the abrading effect of the distichia. How is distichiasis diagnosed? Distichia may be seen with the naked eye with very close inspection.
    [Show full text]
  • Canine Red Eye Elizabeth Barfield Laminack, DVM; Kathern Myrna, DVM, MS; and Phillip Anthony Moore, DVM, Diplomate ACVO
    PEER REVIEWED Clinical Approach to the CANINE RED EYE Elizabeth Barfield Laminack, DVM; Kathern Myrna, DVM, MS; and Phillip Anthony Moore, DVM, Diplomate ACVO he acute red eye is a common clinical challenge for tion of the deep episcleral vessels, and is characterized general practitioners. Redness is the hallmark of by straight and immobile episcleral vessels, which run Tocular inflammation; it is a nonspecific sign related 90° to the limbus. Episcleral injection is an external to a number of underlying diseases and degree of redness sign of intraocular disease, such as anterior uveitis and may not reflect the severity of the ocular problem. glaucoma (Figures 3 and 4). Occasionally, episcleral Proper evaluation of the red eye depends on effective injection may occur in diseases of the sclera, such as and efficient diagnosis of the underlying ocular disease in episcleritis or scleritis.1 order to save the eye’s vision and the eye itself.1,2 • Corneal Neovascularization » Superficial: Long, branching corneal vessels; may be SOURCE OF REDNESS seen with superficial ulcerative (Figure 5) or nonul- The conjunctiva has small, fine, tortuous and movable vessels cerative keratitis (Figure 6) that help distinguish conjunctival inflammation from deeper » Focal deep: Straight, nonbranching corneal vessels; inflammation (see Ocular Redness algorithm, page 16). indicates a deep corneal keratitis • Conjunctival hyperemia presents with redness and » 360° deep: Corneal vessels in a 360° pattern around congestion of the conjunctival blood vessels, making the limbus; should arouse concern that glaucoma or them appear more prominent, and is associated with uveitis (Figure 4) is present1,2 extraocular disease, such as conjunctivitis (Figure 1).
    [Show full text]
  • Congenital Ocular Anomalies in Newborns: a Practical Atlas
    www.jpnim.com Open Access eISSN: 2281-0692 Journal of Pediatric and Neonatal Individualized Medicine 2020;9(2):e090207 doi: 10.7363/090207 Received: 2019 Jul 19; revised: 2019 Jul 23; accepted: 2019 Jul 24; published online: 2020 Sept 04 Mini Atlas Congenital ocular anomalies in newborns: a practical atlas Federico Mecarini1, Vassilios Fanos1,2, Giangiorgio Crisponi1 1Neonatal Intensive Care Unit, Azienda Ospedaliero-Universitaria Cagliari, University of Cagliari, Cagliari, Italy 2Department of Surgery, University of Cagliari, Cagliari, Italy Abstract All newborns should be examined for ocular structural abnormalities, an essential part of the newborn assessment. Early detection of congenital ocular disorders is important to begin appropriate medical or surgical therapy and to prevent visual problems and blindness, which could deeply affect a child’s life. The present review aims to describe the main congenital ocular anomalies in newborns and provide images in order to help the physician in current clinical practice. Keywords Congenital ocular anomalies, newborn, anophthalmia, microphthalmia, aniridia, iris coloboma, glaucoma, blepharoptosis, epibulbar dermoids, eyelid haemangioma, hypertelorism, hypotelorism, ankyloblepharon filiforme adnatum, dacryocystitis, dacryostenosis, blepharophimosis, chemosis, blue sclera, corneal opacity. Corresponding author Federico Mecarini, MD, Neonatal Intensive Care Unit, Azienda Ospedaliero-Universitaria Cagliari, University of Cagliari, Cagliari, Italy; tel.: (+39) 3298343193; e-mail: [email protected].
    [Show full text]
  • Lid Splitting and Posterior Lamellar Cryotherapy for Congenital Distichiasis and Trichiasis in Dog
    Scientific Works. Series C. Veterinary Medicine. Vol. LXI (1) ISSN 2065-1295; ISSN 2343-9394 (CD-ROM); ISSN 2067-3663 (Online); ISSN-L 2065-1295 LID SPLITTING AND POSTERIOR LAMELLAR CRYOTHERAPY FOR CONGENITAL DISTICHIASIS AND TRICHIASIS IN DOG 1Andra ENACHE, 2Pip BOYDELL, 1Iuliana IONAŞCU, 1Alexandru ŞONEA 1University of Agronomical Sciences and Veterinary Medicine, Faculty of Veterinary Medicine, Bucharest, Romania, [email protected] 2 Animal Medical Centre Referral Services, Manchester, United Kingdom Corresponding author email: [email protected] Abstract Various surgical techniques have been proposed for treating distichiasis in dogs. A technique involving eyelid splitting and double freeze-thaw cryotherapy with anterior lamellar recession was evaluated. A 3 year old, female, Staffordshire bull terrier was referred for bilateral distichiasis. There were bilateral multiple distichiasis of the upper lids, more severe on the right lid with double row of cilia and two cilia on the lower lid. Under general anaesthesia, the eyelid margin was split at the gray line and a cryoprobe was used to freeze the posterior lamella. A double freeze-thaw technique was applied in both eyes. Anterior lamellar recession was performed to prevent postoperative entropion with trichiasis. The anterior and posterior lamellas were sutured with a 6/0 Vicryl suture. Bilateral upper eyelid edema was noted postoperatively. A month follow-up revealed increased bilateral granulation and depigmentation and the recurrence of one follicle on the right upper lid. Five months postoperatively there was no recurrence in the left eye but three cilia were detected in the right upper lid. The follicles have regrown due to incomplete destruction of the roots.
    [Show full text]
  • The Management of Congenital Malpositions of Eyelids, Eyes and Orbits
    Eye (\988) 2, 207-219 The Management of Congenital Malpositions of Eyelids, Eyes and Orbits S. MORAX AND T. HURBLl Paris Summary Congenital malformations of the eye and its adnexa which are multiple and varied can affect the whole eyeball or any part of it, as well as the orbit, eyelids, lacrimal ducts, extra-ocular muscles and conjunctiva. A classification of these malformations is presented together with the general principles of treatment, age of operating and surgical tactics. The authors give some examples of the anatomo-clinical forms, eyelid malpositions such as entropion, ectropion, ptosis, levator eyelid retraction, medial canthus malposition, congenital eyelid colobomas, and congenital orbital abnormalities (Craniofacial stenosis, orbi­ tal plagiocephalies, hypertelorism, anophthalmos, microphthalmos and cryptophthalmos) . Congenital malformations of the eye and its as echography, CT-scan and NMR, enzymatic adnexa are multiple and varied. They can work-up or genetic studies (Table I). affect the whole eyeball or any part of it, as Surgical treatment when feasible will well as the orbit, eyelids, lacrimal ducts extra­ encounter numerous problems; age will play a ocular muscles and conjunctiva. role, choice of a surgical protocol directly From the anatomical point of view, the fol­ related to the existing complaints, and coop­ lowing can be considered. eration between several surgical teams Position abnormalities (malpositions) of (ophthalmologic, plastic, cranio-maxillo-fac­ one or more elements and formation abnor­ ial and neurosurgical), the ideal being to treat malities (malformations) of the same organs. Some of these abnormalities are limited to Table I The manag ement of cong enital rna/positions one organ and can be subjected to a relatively of eyelid s, eyes and orbits simple and well recognised surgical treat­ Ocular Findings: ment.
    [Show full text]
  • Ocular Colobomaâ
    Eye (2021) 35:2086–2109 https://doi.org/10.1038/s41433-021-01501-5 REVIEW ARTICLE Ocular coloboma—a comprehensive review for the clinician 1,2,3 4 5 5 6 1,2,3,7 Gopal Lingam ● Alok C. Sen ● Vijaya Lingam ● Muna Bhende ● Tapas Ranjan Padhi ● Su Xinyi Received: 7 November 2020 / Revised: 9 February 2021 / Accepted: 1 March 2021 / Published online: 21 March 2021 © The Author(s) 2021. This article is published with open access Abstract Typical ocular coloboma is caused by defective closure of the embryonal fissure. The occurrence of coloboma can be sporadic, hereditary (known or unknown gene defects) or associated with chromosomal abnormalities. Ocular colobomata are more often associated with systemic abnormalities when caused by chromosomal abnormalities. The ocular manifestations vary widely. At one extreme, the eye is hardly recognisable and non-functional—having been compressed by an orbital cyst, while at the other, one finds minimalistic involvement that hardly affects the structure and function of the eye. In the fundus, the variability involves the size of the coloboma (anteroposterior and transverse extent) and the involvement of the optic disc and fovea. The visual acuity is affected when coloboma involves disc and fovea, or is complicated by occurrence of retinal detachment, choroidal neovascular membrane, cataract, amblyopia due to uncorrected refractive errors, etc. While the basic birth anomaly cannot be corrected, most of the complications listed above are correctable to a great 1234567890();,: 1234567890();,: extent. Current day surgical management of coloboma-related retinal detachments has evolved to yield consistently good results. Cataract surgery in these eyes can pose a challenge due to a combination of microphthalmos and relatively hard lenses, resulting in increased risk of intra-operative complications.
    [Show full text]
  • International Classification of Diseases
    INTERNATIONAL CLASSIFICATION OF DISEASES MANUAL OF THE INTERNATIONAL STATISTICAL CLASSIFICATION OF DISEASES, INJURIES, AND CAUSES OF DEATH Based on the Recommendations of the Eighth Revision Conference, 1965, and Adopted by the Nineteenth World Health Assembly Volume 2 ALPHABETICAL INDEX WORLD HEALTH ORGANIZATION GENEVA 1969 Volume 1 Introduction List of Three-digit Categories Tabular List of Inclusions and Four-digit Sub- categories Medical Certification and Rules for Classification Special Lists for Tabulation Definitions and Recommendations Regulations Volume 2 Alphabetical Index PRINTED IN ENGLAND CONTENTS Introduction Page General arrangement of the Index ....................................... VIII Main sections ............................................................... VIII Structure ..................................................................... IX Code numbzrs .............................................................. x Primary and secondary conditions. ................................... x Multiple diagnoses. ........................................................ XI Spelling....................................................................... XI Order of listing ............................................................. Conventions used in the Index ........................................... XII Parentheses. ................................................................. XII Cross-referexes ........................................................... XI1 Abbreviation NEC. ......................................................
    [Show full text]
  • One-Stage Correction for Blepharophimosis Syndrome
    Eye (2008) 22, 380–388 & 2008 Nature Publishing Group All rights reserved 0950-222X/08 $30.00 www.nature.com/eye CLINICAL STUDY One-stage S-Y Wu, L Ma, Y-J Tsai and JZ-C Kuo correction for blepharophimosis syndrome Abstract Introduction Purpose To classify the severity of Blepharophimosis-ptosis-epicanthus inversus blepharophimosis, describe associated (BPES) syndrome is a rare congenital disorder features and their effects on the incidence of and occurs either as an autosomal dominant amblyopia and to recommend guidelines for trait or sporadically.1–6 In 1971, Kohn and surgical treatment and management of surgical Romano2 described the tetrad of this complications. syndrome, which includes blepharophimosis, Methods The case records of 23 patients with blepharoptosis, epicanthus inversus, and blepharophimosis syndrome were examined telecanthus. It is also associated with ocular, retrospectively. Patients’ photographs and lacrimal, nasal, and auricular anomalies.4–6 measurements were reviewed to analyse the There are two subtypes of this syndrome severity of blepharophimosis, surgical proposed by Zlotogora et al:3 type I is more techniques undertaken, surgical outcomes, prevalent and affected female subjects are and complications. Statistical analyses were infertile and type II is transmitted both in performed using paired-sample t-tests to affected male and female subjects.3 evaluate the surgical outcome and Spearman Blepharophimosis syndrome (BPES) has a correlation to examine the influence of great impact on a patient’s functional status and blepharophimosis on the interpalpebral may cause poor visual development.7 Although fissure height (PFH). previous studies describe the demography and Results Eighteen out of 23 (78%) patients aetiology of children with blepharophimosis underwent one-stage surgery before the age syndrome,1–6,8–11 there is a little information in of 5 years.
    [Show full text]
  • Spectrum of Genetic Variants Associated with Anterior Segment Dysgenesis in South Florida
    G C A T T A C G G C A T genes Article Spectrum of Genetic Variants Associated with Anterior Segment Dysgenesis in South Florida Saradadevi Thanikachalam 1, Elizabeth Hodapp 2, Ta C. Chang 2 , Dayna Morel Swols 3, Filiz B. Cengiz 1, Shengru Guo 1, Mohammad F. Zafeer 1, Serhat Seyhan 1, Guney Bademci 1, William K. Scott 1,3, Alana Grajewski 2 and Mustafa Tekin 1,2,3,* 1 John P. Hussmann Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136, USA; [email protected] (S.T.); [email protected] (F.B.C.); [email protected] (S.G.); [email protected] (M.F.Z.); [email protected] (S.S.); [email protected] (G.B.); [email protected] (W.K.S.) 2 Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA; [email protected] (E.H.); [email protected] (T.C.C.); [email protected] (A.G.) 3 Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL 33136, USA; [email protected] * Correspondence: [email protected] Received: 7 February 2020; Accepted: 25 March 2020; Published: 26 March 2020 Abstract: Anterior segment dysgenesis (ASD) comprises a wide spectrum of developmental conditions affecting the cornea, iris, and lens, which may be associated with abnormalities of other organs. To identify disease-causing variants, we performed exome sequencing in 24 South Florida families with ASD. We identified 12 likely causative variants in 10 families (42%), including single nucleotide or small insertion–deletion variants in B3GLCT, BMP4, CYP1B1, FOXC1, FOXE3, GJA1, PXDN, and TP63, and a large copy number variant involving PAX6.
    [Show full text]