|
1
|
Goyal S, Tibrewal S, Ratna R, Vanita V. Genetic and environmental factors contributing to anophthalmia and microphthalmia: Current understanding and future directions. World J Clin Pediatr 2025; 14:101982. [DOI: 10.5409/wjcp.v14.i2.101982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Revised: 02/19/2025] [Accepted: 02/25/2025] [Indexed: 03/18/2025] Open
Abstract
Anophthalmia is defined as a complete absence of one eye or both the eyes, while microphthalmia represents the presence of a small eye within the orbit. The estimated birth prevalence for anophthalmia is approximately 3 per 100000 live births, and for microphthalmia, it is around 14 per 100000 live births. However, combined evidence suggests that the prevalence of these malformations could be as high as 30 per 100000 individuals. Microphthalmia is reported to occur in 3.2% to 11.2% of blind children. Anophthalmia and microphthalmia (A/M) are part of a phenotypic spectrum alongside ocular coloboma, hypothesized to share a common genetic basis. Both A/M can occur in isolation or as part of a syndrome. Their complex etiology involves chromosomal aberrations, monogenic inheritance pattern, and the contribution of environmental factors such as gestational-acquired infections, maternal vitamin A deficiency (VAD), exposure to X-rays, solvent misuse, and thalidomide exposure. A/M exhibit significant clinical and genetic heterogeneity with over 90 genes identified so far. Familial cases of A/M have a complex genetic basis, including all Mendelian modes of inheritance, i.e., autosomal dominant, recessive, and X-linked. Most cases arise sporadically due to de novo mutations. Examining gene expression during eye development and the effects of various environmental variables will help us better understand the phenotypic heterogeneity found in A/M, leading to more effective diagnosis and management strategies. The present review focuses on key genetic factors, developmental abnormalities, and environmental modifiers linked with A/M. It also emphasizes at potential research areas including multiomic methods and disease modeling with induced pluripotent stem cell technologies, which aim to create innovative treatment options.
Collapse
Affiliation(s)
- Shiwali Goyal
- Department of Ophthalmic Genetics and Visual Function Branch, National Eye Institute, Rockville, MD 20852, United States
| | - Shailja Tibrewal
- Department of Pediatric Ophthalmology, Dr. Shroff’s Charity Eye Hospital, New Delhi 110002, Delhi, India
- Department of Ocular Genetics (Center for Unknown and Rare Eye Diseases), Dr. Shroff’s Charity Eye Hospital, New Delhi 110002, Delhi, India
| | - Ria Ratna
- Department of Ocular Genetics (Center for Unknown and Rare Eye Diseases), Dr. Shroff’s Charity Eye Hospital, New Delhi 110002, Delhi, India
| | - Vanita Vanita
- Department of Human Genetics, Guru Nanak Dev University, Amritsar 143005, Punjab, India
| |
Collapse
|
|
2
|
Elsayed MEA, Lander B, Senthil S, Edward DP, Malik R. The secondary childhood glaucomas. Surv Ophthalmol 2025; 70:544-562. [PMID: 39486644 DOI: 10.1016/j.survophthal.2024.10.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 10/18/2024] [Accepted: 10/28/2024] [Indexed: 11/04/2024]
Abstract
The secondary childhood glaucomas are a heterogenous group, often associated with other ocular or systemic abnormalities. These childhood glaucomas are distinct from primary childhood glaucomas, both in terms of their clinical features and their response to conventional treatment. Surgical management can be challenging in children with secondary glaucoma. On average, this group undergo more surgical procedures and revisions than those with primary congenital glaucoma. We provide a synopsis of secondary childhood glaucomas in terms of classification, clinical features, and management strategies, with emphasis on recent developments.
Collapse
Affiliation(s)
| | | | | | - Deepak P Edward
- Glaucoma Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia; Dept of Ophthalmology and Visual Sciences, University of Illinois Eye and Ear Infirmary, Chicago, USA
| | - Rizwan Malik
- Glaucoma Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
| |
Collapse
|
|
3
|
Dubucs C, Caillet A, Frémont F, Delteil L, N'Go V, Neville AJ, Ballardini E, Dolk H, Loane M, Garne E, Khoshnood B, Lelong N, Rissmann A, O'Mahony M, Pierini A, Gatt M, Bergman J, Krawczynski MR, Latos Bielenska A, Echevarría González de Garibay LJ, Cavero‐Carbonell C, Addor M, Tucker D, Jordan S, Den Hond E, Nelen V, Barisic I, Rouget F, Randrianaivo H, Hoareau J, Perthus I, Hurault‐Delarue C, Courtade‐Saïdi M, Damase‐Michel C. Prevalence of Congenital Ocular Anomalies in 15 Countries of Europe: Results From the Medikeye Study. Birth Defects Res 2024; 116:e2414. [PMID: 39582415 PMCID: PMC11586828 DOI: 10.1002/bdr2.2414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Revised: 10/10/2024] [Accepted: 10/22/2024] [Indexed: 11/26/2024]
Abstract
BACKGROUND Congenital ocular anomalies (COA) are among the most common causes of visual impairment in children in high-income countries. The aim of the study is to describe the prevalence of the various COA recorded in European population-based registries of CA (EUROCAT) participating in the EUROmediCAT consortium. METHODS Data from 19 EUROmediCAT registries and one healthcare database (EFEMERIS) were included in this descriptive epidemiological study. Cases of COA included live births, FD from 20 weeks gestational age (GA), and termination of pregnancy for fetal anomaly. RESULTS The prevalence of total COA was 3.47/10,000 births (95% CI [3.61-3.82]), ranging from 1.41 to 13.46/10,000 depending on the registry. Among COA cases, congenital lens anomalies were the most frequent anomalies (31%), of which over half were single ocular anomalies (presenting with only one ocular anomaly). An/microphthalmia was the second most frequent COA (24%) of which three-quarters were multiply malformed (associated to extraocular major anomalies). Among single COA cases, 58 were prenatally diagnosed (4%), of which, 58% were diagnosed in the second trimester. Known genetic causes of COA explained 2.5%-25% of COA depending on their class. CONCLUSIONS This is the first European study describing COA. The detailed prevalence data offered in this study could improve screening and early diagnosis of different classes of COA. As COA are rare, epidemiological surveillance of large populations and accurate clinical descriptions are essential.
Collapse
Affiliation(s)
- Charlotte Dubucs
- Unité de PharmacoépidémiologieUMR CERPOP, INSERM, Université de ToulouseToulouseFrance
- Département d'Anatomie et Cytologie PathologiquesIUCT‐OncopoleToulouseFrance
- Faculté de SantéDépartement MMPToulouseFrance
| | - Anthony Caillet
- Unité de PharmacoépidémiologieUMR CERPOP, INSERM, Université de ToulouseToulouseFrance
| | - Félix Frémont
- Service d'ophtalmologieHôpital Pierre‐Paul Riquet, CHU Toulouse‐PurpanToulouseFrance
- Clinique Honoré CaveMontaubanFrance
| | - Laurane Delteil
- Unité de PharmacoépidémiologieUMR CERPOP, INSERM, Université de ToulouseToulouseFrance
| | - Van N'Go
- Unité de PharmacoépidémiologieUMR CERPOP, INSERM, Université de ToulouseToulouseFrance
| | - Amanda Julie Neville
- Centre for Clinical and Epidemiological ResearchUniversity of Ferrara and Azienda, Ospedaliero Universitario di FerraraFerraraItaly
| | - Elisa Ballardini
- Neonatal Intensive Care UnitUniversity Hospital of Ferrara, IMER Registry (Emilia Romagna Registry of Birth Defects)FerraraItaly
- Department of Medical SciencesUniversity of FerraraFerraraItaly
| | - Helen Dolk
- School of MedicineUlster UniversityBelfastNorthern IrelandUK
| | - Maria Loane
- Institute of Nursing and Health ResearchUlster UniversityBelfastNorthern IrelandUK
| | - Ester Garne
- Department of Paediatrics and Adolescent MedicineLillebaelt Hospital, University Hospital of Southern DenmarkKoldingDenmark
| | | | | | - Anke Rissmann
- Malformation Monitoring Centre Saxony‐Anhalt, Medical Faculty Otto‐von‐Guericke‐University MagdeburgMagdeburgGermany
| | - Mary O'Mahony
- Department of Public HealthSt. Finbarr's HospitalCorkIreland
| | - Anna Pierini
- Unit of Epidemiology of Rare Diseases and CAInstitute of Clinical Physiology‐National Research CouncilPisaItaly
| | - Miriam Gatt
- Malta CA Register, Directorate for Health Information and ResearchPietàMalta
| | - Jorieke Bergman
- Department of GeneticsUniversity of Groningen, University Medical Center GroningenGroningenThe Netherlands
| | | | | | | | - Clara Cavero‐Carbonell
- Rare Diseases Research UnitFoundation for the Promotion of Health and Biomedical Research in the Valencian RegionValenciaSpain
| | - Marie‐Claude Addor
- Department of Woman‐Mother‐ChildCentre Hospitalier Universitaire Vaudois (CHUV)LausanneSwitzerland
| | - David Tucker
- Public Health Wales, Public Health Knowledge and ResearchSingleton HospitalSwanseaWalesUK
| | - Sue Jordan
- Faculty of Medicine, Health and Life ScienceSwansea UniversitySwanseaWalesUK
| | | | - Vera Nelen
- Provincial Institute of HygieneAntwerpBelgium
| | - Ingeborg Barisic
- Centre of Excellence for Reproductive and Regenerative MedicineMedical School University of ZagrebZagrebCroatia
| | | | - Hanitra Randrianaivo
- Unit of Congenital MalformationsREMACOR‐Medical School University of La Réunion St. Pierre, Sainte‐Clotilde/Register of Reunion Island CHU LA REUNIONRéunionFrance
| | - Jonathan Hoareau
- Unit of Congenital MalformationsREMACOR‐Medical School University of La Réunion St. Pierre, Sainte‐Clotilde/Register of Reunion Island CHU LA REUNIONRéunionFrance
| | - Isabelle Perthus
- Génétique médicale, CHU EstaingCentre d'Etude Des Malformations Congénitales en AuvergneClermont‐FerrandFrance
| | | | - Monique Courtade‐Saïdi
- Département d'Anatomie et Cytologie PathologiquesIUCT‐OncopoleToulouseFrance
- Faculté de SantéDépartement MMPToulouseFrance
| | - Christine Damase‐Michel
- Unité de PharmacoépidémiologieUMR CERPOP, INSERM, Université de ToulouseToulouseFrance
- Service de Pharmacologie Clinique, Faculté de MédecineUniversité de Toulouse, CHU de ToulouseToulouseFrance
| |
Collapse
|
|
4
|
Mitchell DL, Chambers TM, Agopian AJ, Benjamin RH, Shumate CJ, Slavotinek A, Hufnagel RB, Brooks BP, Mitchell LE, Lupo PJ. Epidemiology of Coloboma: Prevalence and Patterns in Texas, 1999-2014. Birth Defects Res 2024; 116:e2413. [PMID: 39530497 DOI: 10.1002/bdr2.2413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Revised: 10/18/2024] [Accepted: 10/21/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Coloboma is a rare congenital malformation in which part of the tissue that makes up the eye is missing and may cause visual impairment or blindness. Little is known about the epidemiology of this condition. Therefore, we obtained data from the Texas Birth Defects Registry on children identified with coloboma for the period 1999-2014. METHODS Using information on all live births from the same period, prevalence ratios (PRs) for selected demographic and clinical factors were used to estimate associations using Poisson regression among cases with coloboma. Coloboma cases were divided into subgroups to explore patterns of co-occurring defects and syndromes. All variables significant in unadjusted models (p < 0.05) were included in multivariable models to evaluate adjusted PRs (aPRs). RESULTS We identified 1587 cases with coloboma, of whom 934 (58.8%) were nonsyndromic, and 474 (29.9%) were isolated. When considering all identified cases, factors associated with significant differences in prevalence included plurality (multiple vs. singleton aPR = 1.4, 95% CI: 1.1-1.8); maternal education (college or greater vs. less than high school aPR = 0.7, 95% CI: 0.6-0.9); maternal race/ethnicity (Hispanic vs. non-Hispanic White aPR = 0.9, 95% CI: 0.8-1.0); and maternal diabetes (yes vs. no aPR = 1.3, 95% CI: 1.0-1.6). There was a notable increase in the birth prevalence of coloboma during the study period (p-for-trend < 0.001). Effect estimates were similar across the different subgroups. CONCLUSION In our large population, we identified several factors associated with the prevalence of coloboma. These findings may help define subgroups of women more likely to have children affected by coloboma, which could inform improved screening efforts.
Collapse
Affiliation(s)
- Danielle L Mitchell
- Section of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
| | - Tiffany M Chambers
- Section of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
| | - A J Agopian
- Department of Epidemiology, University of Texas Health Science Center at Houston (UTHealth) School of Public Health, Houston, Texas, USA
| | - Renata H Benjamin
- Department of Epidemiology, University of Texas Health Science Center at Houston (UTHealth) School of Public Health, Houston, Texas, USA
| | - Charles J Shumate
- Birth Defects Epidemiology and Surveillance Branch, Texas Department of State Health Services, Austin, Texas, USA
| | - Anne Slavotinek
- Division of Human Genetics, Cincinnati Children's Hospital, Cincinnati, Ohio, USA
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | | | - Brian P Brooks
- Ophthalmic Genetics & Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Laura E Mitchell
- Department of Epidemiology, University of Texas Health Science Center at Houston (UTHealth) School of Public Health, Houston, Texas, USA
| | - Philip J Lupo
- Section of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
| |
Collapse
|
|
5
|
Ma L, Hou Z, Zhang J, Li Y, Jiang X, Li D. Stepwise self-inflating hydrogel expansion for congenital anophthalmia and blind microphthalmia: Over 15 years' experience in China. J Plast Reconstr Aesthet Surg 2024; 90:40-46. [PMID: 38354490 DOI: 10.1016/j.bjps.2024.01.053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 01/11/2024] [Accepted: 01/29/2024] [Indexed: 02/16/2024]
Abstract
BACKGROUND Self-inflating hydrogel expanders have been used to treat anophthalmia and blind microphthalmia. This study aimed to investigate the long-term outcomes of treatment with self-inflating hydrogel expanders for congenital anophthalmia and blind microphthalmia. METHODS In this retrospective study, the medical records of 161 patients with anophthalmia and blind microphthalmia who underwent hydrogel expansion were reviewed. We measured the palpebral fissure height (PFH), palpebral fissure length (PFL), and distance between the inner canthal and mid-nasal line (ICMN) before and after surgery. Cox regression analysis was conducted to determine which variables were related to the implantation of spherical expanders following hemispherical expander implantation. RESULTS After treatment, the PFH and PFL increased significantly (p < 0.001). Complications including expander migration and extrusion occurred in 15 cases. Five patients needed enucleation or further dermis fat graft implantation because of insufficient expansion. The necessity for further spherical expansion was substantially related to a relative axial length (rAL) <0.5 (p = 0.007). CONCLUSION Self-inflating hydrogel expansion can significantly increase the lid fissure. The occurrence of complications is rare, and surgical intervention can effectively address them. Abnormal eyes with a rAL of less than 0.5 demonstrate a higher possibility of needing additional orbital expansion.
Collapse
Affiliation(s)
- Lan Ma
- Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Ophthalmology and Visual Science Key Lab, Capital Medical University, Beijing, China
| | - Zhijia Hou
- Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Ophthalmology and Visual Science Key Lab, Capital Medical University, Beijing, China
| | - Ju Zhang
- Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Ophthalmology and Visual Science Key Lab, Capital Medical University, Beijing, China
| | - Yang Li
- Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Ophthalmology and Visual Science Key Lab, Capital Medical University, Beijing, China
| | - Xue Jiang
- Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Ophthalmology and Visual Science Key Lab, Capital Medical University, Beijing, China
| | - Dongmei Li
- Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Ophthalmology and Visual Science Key Lab, Capital Medical University, Beijing, China.
| |
Collapse
|
|
6
|
Stoll C, Dott B, Alembik Y, Roth MP. Associated anomalies in anophthalmia and microphthalmia. Eur J Med Genet 2024; 67:104892. [PMID: 38110175 DOI: 10.1016/j.ejmg.2023.104892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 11/07/2023] [Accepted: 11/25/2023] [Indexed: 12/20/2023]
Abstract
Infants with anophthalmia and microphthalmia (an/microphthalmia) have often other associated congenital anomalies. The reported frequency and the types of these associated anomalies vary between different studies. The purpose of this investigation was to assess the frequency and the types of associated anomalies among cases with an/microphthalmia in a geographically well defined population of northeastern France of 387,067 consecutive pregnancies from 1979 to 2007. Of the 98 infants with an/microphthalmia born during this period (prevalence at birth of 2.53 per 10,000), 88.8 % had associated anomalies. Cases with associated anomalies were divided into recognizable conditions (25 (25.5%) cases with chromosomal and 17 (17.3%) cases with non chromosomal conditions), and non recognizable conditions (45-45.9%- cases with multiple congenital anomalies -MCA). Trisomy 13 and trisomy 18 were the most frequent chromosomal abnormalities. Amniotic bands sequence, oculo-auriculo-vertebral spectrum, CHARGE syndrome and VACTERL association were most often present in recognizable non chromosomal conditions. Anomalies in the musculoskeletal, cardiovascular and central nervous systems were the most common other anomalies in cases with MCA and non recognizable conditions. However, given the limitation of the limited numbers of cases there should be urging caution in interpreting these results. In conclusion the frequency of associated anomalies in infants with anophthalmia and microphthalmia emphasizes the need for a thorough investigation of these cases. Routine screening for other anomalies especially musculoskeletal, cardiac and central nervous systems anomalies may need to be considered in infants with anophthalmia and microphthalmia, and referral of these cases for genetic counselling seems warranty.
Collapse
Affiliation(s)
- Claude Stoll
- Laboratoire de Genetique Medicale, Faculte de Medecine, Strasbourg, France.
| | - Beatrice Dott
- Laboratoire de Genetique Medicale, Faculte de Medecine, Strasbourg, France
| | - Yves Alembik
- Laboratoire de Genetique Medicale, Faculte de Medecine, Strasbourg, France
| | - Marie-Paule Roth
- Laboratoire de Genetique Medicale, Faculte de Medecine, Strasbourg, France
| |
Collapse
|
|
7
|
Parizotto Paula I, Gonçalves Paula R, Kokitsu NM, Alonso N, Tonello C. Clinical Characterization of Congenital Anophthalmic and Microphthalmic Cavities in Inidviduals With Craniofacial Anomalies. J Craniofac Surg 2023; 34:e542-e546. [PMID: 37539939 DOI: 10.1097/scs.0000000000009557] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Accepted: 06/04/2023] [Indexed: 08/05/2023] Open
Abstract
OBJECTIVE Measure the frequency of anophthalmic and microphthalmic patients with craniofacial anomalies (FCAs). DESIGN Descriptive, cross-sectional, retrospective study. SETTING Hospital for Rehabilitation of Craniofacial Anomalies of the University of São Paulo (HRAC-USP). The medical records of patients treated at HRAC from 2000 to 2012 with a diagnosis of congenital anophthalmia or microphthalmia were examined. Patients were excluded for secondary anophthalmia, incomplete medical records, or information that could not be accessed. OUTCOME MEASURES Frequency of anophthalmia and microphthalmia; the proportions and diagnoses of associated FCAs; impairment of ocular appendages; extracranial or facial anomalies; genetic alterations; and surgical approach. RESULTS A total of 56 patients had anophthalmia (52.3%), 35 had microphthalmia (32.7%), and 16 patients had both (15%). Individuals with FCAs associated with microphthalmia, anophthalmia, or both totaled 74, corresponding to 69.2%. Anophthalmia was more likely than microphthalmia to be accompanied by FCAs, at 76.4% of patients ( P < 0.05). Cleft lip and palate were the main malformations associated with anophthalmia (23.64%), with microphthalmia (45%), and with both (44.44%). Reconstructive surgery was done in 63.6% of cases. The ocular attachments were compromised in 71% of cases. Extracraniofacial malformations were found in 9.3% of patients. Only 7 records contained karyotypes, and no changes directly related to anophthalmia or microphthalmia were found. CONCLUSION Anophthalmia is more frequent than microphthalmia and is more often accompanied by FCA. Cleft lip and cleft palate are the most frequent concomitant malformations.
Collapse
Affiliation(s)
| | | | - Nancy Mizue Kokitsu
- Hospital for Rehabilitation of Craniofacial Anomalies, University of São Paulo
| | - Nivaldo Alonso
- Craniofacial Surgeon of Hospital for Rehabilitation of Craniofacial Anomalies and Hospital of Clinics of Medicine Faculty. Professor of Medicine, University of São Paulo
| | - Cristiano Tonello
- Craniofacial Surgeon of the Hospital for Rehabilitation of Craniofacial Anomalies and Professor of Medicine. University of São Paulo, Bauru, SP, Brazil
| |
Collapse
|
|
8
|
Ma L, Li Y, Zhang H, Li L, Deng G, Xu J, Li D. Abnormalities of the contralateral eye in unilateral congenital anophthalmic or blind microphthalmic patients. J AAPOS 2023; 27:34.e1-34.e4. [PMID: 36563895 DOI: 10.1016/j.jaapos.2022.11.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 11/15/2022] [Accepted: 11/15/2022] [Indexed: 12/25/2022]
Abstract
PURPOSE To describe the prevalence, distribution, and features of anterior and posterior segment abnormalities in the contralateral eye in cases unilateral of anophthalmia and blind microphthalmia. METHODS The medical records of patients with unilateral congenital anophthalmia and blind microphthalmia referred to Beijing Tongren Hospital between January 2017 and December 2021 were reviewed retrospectively to investigate the prevalence of abnormalities of the fellow eye. RESULTS A total of 168 patients were included. Of these, 28 (16.7%) had fellow eye abnormalities, 4 (2.4%) with anterior segment involvement in the contralateral eye. All 28 had fundus abnormalities. The most common posterior segment finding was coloboma (7.7%), followed by optic nerve dysplasia (3.0%), familial exudative vitreoretinopathy (FEVR) or FEVR-like fundus (1.8%), morning glory disk anomaly (1.8%), and retinal nerve fiber layer defect (1.2%). High myopia fundus changes (0.6%), retinal folds (0.6%), maculopathy (0.6%), peripapillary staphyloma (0.6%), and Bergmeister optic disk (0.6%) were also noted. CONCLUSIONS Patients with unilateral congenital anophthalmia or blind microphthalmia have a high probability of contralateral eye disease. The most common abnormality is coloboma.
Collapse
Affiliation(s)
- Lan Ma
- Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Ophthalmology and Visual Science Key Lab, Capital Medical University, Beijing, China
| | - Yang Li
- Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Ophthalmology and Visual Science Key Lab, Capital Medical University, Beijing, China
| | - Hanqiao Zhang
- Department of Ophthalmology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Liang Li
- Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Ophthalmology and Visual Science Key Lab, Capital Medical University, Beijing, China
| | - Guangda Deng
- Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Ophthalmology and Visual Science Key Lab, Capital Medical University, Beijing, China
| | - Jie Xu
- Beijing Institute of Ophthalmology, Capital Medical University, Beijing Tongren Hospital, Beijing, China
| | - Dongmei Li
- Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Ophthalmology and Visual Science Key Lab, Capital Medical University, Beijing, China.
| |
Collapse
|
|
9
|
Clinical Congenital Anophthalmos and Microphthalmos-Experiences of Patients and Their Parents after More than 10 Years of Treatment. CHILDREN (BASEL, SWITZERLAND) 2022; 10:children10010034. [PMID: 36670585 PMCID: PMC9856451 DOI: 10.3390/children10010034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 12/14/2022] [Accepted: 12/20/2022] [Indexed: 12/28/2022]
Abstract
Congenital clinical anophthalmos and blind microphthalmos describe the absence of an eye or the presence of a small eye in the orbit. Between 1999 and 2013, 97 children with anophthalmos or microphthalmos were treated with self-inflating, hydrophilic gel expanders at the Rostock Eye Clinic. More than a decade later, this study investigated the perspective of patients and parents regarding the treatment, the surgical outcome, and the emotional and social well-being of the patients. A total of 22 families with 16 patients sighted in the other eye and six patients blind in both eyes participated. Questionnaires were developed, including items on physical, emotional, social, and medical aspects. The patients felt emotionally stable and integrated into their social environment, with no major limitations reported by the majority. These statements were confirmed by most of the parents. Parents (67%) indicated that the success of the operation was already apparent after the first intervention and that the current situation did not play a role in the patients' social environment. The study provided new insights into the therapy results, the postoperative care, and the social and emotional stability of the prosthesis-wearing patients, indicating the chosen expander methods as promising in terms of positive postoperative care.
Collapse
|
|
10
|
De Ruiter BJ, Lesko RP, Knudsen MG, Kamel G, Shah J, Kotha VS, Barmettler A, Prendes MA, Kumar AR, Davidson EH. An age-related algorithm for management of micro-orbitism from anophthalmia: a systematic review with supplemental case reports. Orbit 2022; 41:397-406. [PMID: 35298326 DOI: 10.1080/01676830.2022.2043391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Accepted: 02/12/2022] [Indexed: 06/14/2023]
Abstract
Management of pediatric anophthalmia and resultant micro-orbitism is challenging. The efficacy and safety of treatment methods vary with age as bony changes grow recalcitrant to implants in those at skeletal maturity and osteotomies become technically challenging following frontal sinus pneumatization. This study aims to review methods for managing micro-orbitism and develop an age-based treatment approach. A systematic literature review was conducted. Data were screened and extracted by two investigators and relevant English-language primary-literature was analyzed. Information on sample-size, number of orbits, intervention, age, complications, and prosthetic retention was obtained. Representative case reports are presented, in addition. Nineteen studies met inclusion: 294 orbits in 266 patients were treated. Two studies reported distraction-osteogenesis. Two studies utilized bone grafting. Osteotomies were performed in 41 patients from three studies. Use of solid implants was detailed in two studies. Three studies described osmotic implant. Four studies described inflatable implants. Other techniques were described by three of the included studies, two of which utilized dermis-fat grafting. All but one study were observational case reports or case series. Across all studies regardless of surgical technique, risk of bias and heterogeneity was high due to attrition bias and selective outcomes-reporting. Selection of therapy should be tailored to skeletal-age to optimize outcomes; those 0-4 yrs are managed with dermis-fat grafts, 5-7 yrs managed with implants, and 8+ yrs managed with osteotomies. For those 8+ yrs with aerated frontal sinuses or insufficient bone stock, we propose onlay camouflage prosthetics which improve projection, increase orbital volume, and avoid risk for frontal sinus injury.
Collapse
Affiliation(s)
- Brandon J De Ruiter
- Department of Plastic and Reconstructive Surgery, Case Western Reserve University, Cleveland, Ohio, USA
| | - Robert P Lesko
- Division of Plastic and Reconstructive Surgery, Montefiore Medical Center/Albert Einstein College of Medicine, New York, New York, USA
| | - M Grace Knudsen
- Department of Plastic and Reconstructive Surgery, Case Western Reserve University, Cleveland, Ohio, USA
| | - George Kamel
- Department of Surgery, Joe DiMaggio Children's Hospital, Fort Lauderdale, Florida, USA
| | - Jinesh Shah
- Division of Plastic and Reconstructive Surgery, Montefiore Medical Center/Albert Einstein College of Medicine, New York, New York, USA
| | - Vikas S Kotha
- Department of Plastic and Reconstructive Surgery, Case Western Reserve University, Cleveland, Ohio, USA
| | - Anne Barmettler
- Department of Ophthalmology and Visual Sciences, Montefiore Medical Center/Albert Einstein College of Medicine, New York, New York, USA
| | - Mark A Prendes
- Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio, USA
| | - Anand R Kumar
- Department of Plastic and Reconstructive Surgery, Case Western Reserve University, Cleveland, Ohio, USA
| | - Edward H Davidson
- Department of Plastic and Reconstructive Surgery, Case Western Reserve University, Cleveland, Ohio, USA
| |
Collapse
|
|
11
|
Kokhanov A. Congenital Abnormalities in the Infant of a Diabetic Mother. Neoreviews 2022; 23:e319-e327. [PMID: 35490182 DOI: 10.1542/neo.23-5-e319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Diabetes mellitus is among the most common chronic diseases worldwide. Infants of diabetic mothers are at increased risk of having congenital abnormalities. Tremendous progress has been achieved in the pregnancy care of diabetic women; however, the risk of birth defects associated with maternal diabetes still exists. These anomalies might arise in many organs and systems of the developing fetus. Many mechanisms have been implicated in the teratogenicity of maternal diabetes and it is critical to achieve good glycemic control before conception in women with diabetes. Neonatal clinicians must be able to identify patients at risk and recognize the signs of diabetic embryopathy. This article presents a review of congenital anomalies associated with maternal diabetes.
Collapse
Affiliation(s)
- Artemiy Kokhanov
- Department of Neonatology, Memorial Care Miller Children's and Women's Hospital Long Beach, Long Beach, CA
| |
Collapse
|
|
12
|
Demographics and histopathological characteristics of enucleated microphthalmic globes. Sci Rep 2022; 12:5283. [PMID: 35347187 PMCID: PMC8960817 DOI: 10.1038/s41598-022-09261-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Accepted: 03/21/2022] [Indexed: 01/25/2023] Open
Abstract
Microphthalmia is a rare ocular anomaly with a poorly understood etiology that is most likely related to heritable and/or environmental factors. Many papers have been published pertaining to the clinical manifestations and management of this condition; however, few reports have reported detailed histopathological findings, which are the focus of this study, in addition to highlighting the basic demographics in these cases. This was a retrospective, observational study of all consecutive enucleated microphthalmic globes (with or without cysts) at 2 tertiary eye hospitals in Riyadh, Saudi Arabia. Globes were classified into 2 groups: severe microphthalmos (axial length or mean diameter less than 10 mm in infancy or 12 mm after age 1 year) and mild microphthalmos based on larger measurements. Clinical and demographic data collected included sex, age at enucleation, eye involvement, nationality/region, consanguinity, family history of eye anomaly, pregnancy, systemic disease, or syndromes. For histopathological data, a descriptive analysis was mostly performed. For correlations of some of our qualitative data, Fisher's exact test was used. Eleven cases (6 mild and 5 severe microphthalmos) were initially identified with a female to male ratio of 4:7. Ten patients were Saudis, 7 of whom were from the central region. Consanguinity was found in 36% (4/11), and 3 of them had other ocular or systemic abnormalities (duodenal atresia, microcephaly, kidney agenesis, cryptophthalmos, and dysmorphic facial features). Histopathological data were available for 10 cases, half of which showed a coloboma and/or anterior segment anomaly. There was no significant correlation among gender, severity of microphthalmos or the presence of coloboma, although severe microphthalmic globes had a higher median of abnormal intraocular structures (9-interquartile range = 2 compared to 6-interquartile range = 1 in the mild group). Aphakia was found in half of the globes with associated anterior segment dysgenesis. We have concluded that microphthalmos is a visually disabling congenital anomaly that can be isolated or associated with other periocular or systemic anomalies, possibly in relation to consanguinity in our cases. Congenital aphakia was found in half of these cases and was mostly associated with absent Descemet's membrane and agenesis of anterior chamber angle structures, supporting previously suggested embryological concepts. These findings necessitate further wider genetic testing and proper premarital counseling in Saudi Arabia.
Collapse
|
|
13
|
Boerkoel PK, Dixon K, Fitzsimons C, Shen Y, Huynh S, Schlade-Bartusiak K, Culibrk L, Chan S, Boerkoel CF, Jones SJM, Chin HL. Long-read genome sequencing resolves a complex 13q structural variant associated with syndromic anophthalmia. Am J Med Genet A 2022; 188:1589-1594. [PMID: 35122461 DOI: 10.1002/ajmg.a.62676] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 12/31/2021] [Accepted: 01/08/2022] [Indexed: 11/05/2022]
Abstract
Microphthalmia, anophthalmia, and coloboma (MAC) are a heterogeneous spectrum of anomalous eye development and degeneration with genetic and environmental etiologies. Structural and copy number variants of chromosome 13 have been implicated in MAC; however, the specific loci involved in disease pathogenesis have not been well-defined. Herein we report a newborn with syndromic degenerative anophthalmia and a complex de novo rearrangement of chromosome 13q. Long-read genome sequencing improved the resolution and clinical interpretation of a duplication-triplication/inversion-duplication (DUP-TRP/INV-DUP) and terminal deletion. Sequence features at the breakpoint junctions suggested microhomology-mediated break-induced replication (MMBIR) of the maternal chromosome as the origin. Comparing this rearrangement to previously reported copy number alterations in 13q, we refine a putative dosage-sensitive critical region for MAC that might provide new insights into its molecular etiology.
Collapse
Affiliation(s)
- Pierre K Boerkoel
- MD Undergraduate Program, University of British Columbia, Vancouver, British Columbia, Canada
| | - Katherine Dixon
- Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.,Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada
| | | | - Yaoqing Shen
- Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada
| | - Stephanie Huynh
- Provincial Medical Genetics Program, Women's Hospital of British Columbia, Vancouver, British Columbia, Canada
| | - Kamilla Schlade-Bartusiak
- Department of Pathology, BC Children's Hospital, BC Women's Hospital & Health Centre, Vancouver, British Columbia, Canada
| | - Luka Culibrk
- Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada
| | - Simon Chan
- Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada
| | - Cornelius F Boerkoel
- Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.,Provincial Medical Genetics Program, Women's Hospital of British Columbia, Vancouver, British Columbia, Canada
| | - Steven J M Jones
- Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.,Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada
| | - Hui-Lin Chin
- Provincial Medical Genetics Program, Women's Hospital of British Columbia, Vancouver, British Columbia, Canada.,Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, Singapore, Singapore
| |
Collapse
|
|
14
|
Fahnehjelm C, Dafgård Kopp E, Wincent J, Güven E, Nilsson M, Olsson M, Teär Fahnehjelm K. Anophthalmia and microphthalmia in children: associated ocular, somatic and genetic morbidities and quality of life. Ophthalmic Genet 2022; 43:172-183. [PMID: 35105264 DOI: 10.1080/13816810.2021.1989600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
PURPOSE To report ocular outcome, somatic co-morbidities, genetics, and quality of life in children born with anophthalmia (A) or microphthalmia (M). METHODS Thirty-five children (19 boys) with A/M underwent ophthalmological examinations and a review of medical records. Parents of 12/22 cases completed the Pediatric Quality of Life Inventory (PedsQL). RESULTS Age at examination ranged from 7 months to 18 years (median 2.3 years). Ten cases were totally blind or had light perception. Isolated A/M occurred in 16/35 cases, while somatic, psychomotor, neuroradiological and/or genetic pathology occurred in 19/35 cases both in the bilateral (7/9) and in the unilateral group (12/26). Among 26 unilateral cases, 4/16 with one normal eye had associated problems compared to 9/10 if the contralateral eye was pathological (p < .01). There was an increased risk for heart defects in children with psychomotor delay (p = .04). Pathogenic genetic abnormalities were identified in 10/24 cases. Neuroimaging demonstrated pathology in 14/20 cases with corpus callosum dysgenesis (6/20) being the most common. The median total PedsQL score of parent reports for ages 2-12 was 52.4 (range 22.6-100). CONCLUSIONS Somatic, psychomotor and/or neuroradiological pathologies were more common in bila-teral than unilateral cases, but the difference was not significant. There was decreased risk in unilateral cases with one normal eye. Genetic defects occurred in both unilateral and bilateral cases. Health-related quality of life was reduced.
Collapse
Affiliation(s)
- Cecilia Fahnehjelm
- Department of Paediatrics, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden
| | - Eva Dafgård Kopp
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.,Department of Oculoplastic and Orbital Services, St. Erik Eye Hospital, Stockholm, Sweden
| | - Josephine Wincent
- Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.,Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden
| | - Evin Güven
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.,Department of Paediatric Ophthalmology, Strabismus and Electrophysiology, St. Erik Eye Hospital, Stockholm, Sweden
| | - Mattias Nilsson
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - Monica Olsson
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.,Department of Paediatric Ophthalmology, Strabismus and Electrophysiology, St. Erik Eye Hospital, Stockholm, Sweden
| | - Kristina Teär Fahnehjelm
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.,Department of Paediatric Ophthalmology, Strabismus and Electrophysiology, St. Erik Eye Hospital, Stockholm, Sweden
| |
Collapse
|
|
15
|
Normal Retinotopy in Primary Visual Cortex in a Congenital Complete Unilateral Lesion of Lateral Geniculate Nucleus in Human: A Case Study. Int J Mol Sci 2022; 23:ijms23031055. [PMID: 35162977 PMCID: PMC8835673 DOI: 10.3390/ijms23031055] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 01/14/2022] [Accepted: 01/15/2022] [Indexed: 11/17/2022] Open
Abstract
Impairment of the geniculostriate pathway results in scotomas in the corresponding part of the visual field. Here, we present a case of patient IB with left eye microphthalmia and with lesions in most of the left geniculostriate pathway, including the Lateral Geniculate Nucleus (LGN). Despite the severe lesions, the patient has a very narrow scotoma in the peripheral part of the lower-right-hemifield only (beyond 15° of eccentricity) and complete visual field representation in the primary visual cortex. Population receptive field mapping (pRF) of the patient’s visual field reveals orderly eccentricity maps together with contralateral activation in both hemispheres. With diffusion tractography, we revealed connections between superior colliculus (SC) and cortical structures in the hemisphere affected by the lesions, which could mediate the retinotopic reorganization at the cortical level. Our results indicate an astonishing case for the flexibility of the developing retinotopic maps where the contralateral thalamus receives fibers from both the nasal and temporal retinae.
Collapse
|
|
16
|
A Fetus with Congenital Microcephaly, Microphthalmia and Cataract Was Detected with Biallelic Variants in the OCLN Gene: A Case Report. Diagnostics (Basel) 2021; 11:diagnostics11091576. [PMID: 34573918 PMCID: PMC8472215 DOI: 10.3390/diagnostics11091576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 08/18/2021] [Accepted: 08/25/2021] [Indexed: 11/17/2022] Open
Abstract
Microcephaly and microphthalmia are both rare congenital abnormalities, while concurrently, these two are even rarer. The underlying etiology would be complex interplaying between heterogeneous genetic background and the environmental pathogens, particularly during critical periods of early tissue development. Here, we reported a prenatal case with microcephaly, microphthalmia, and bilateral cataracts detected by ultrasonography and confirmed by autopsy. Various routine infection-related tests and invasive genetic testing were negative. Whole genome sequencing of fetus and parents revealed OCLN gene defects may be associated with these multiple congenital abnormalities.
Collapse
|
|
17
|
Harding P, Toms M, Schiff E, Owen N, Bell S, Lloyd IC, Moosajee M. EPHA2 Segregates with Microphthalmia and Congenital Cataracts in Two Unrelated Families. Int J Mol Sci 2021; 22:2190. [PMID: 33671840 PMCID: PMC7926380 DOI: 10.3390/ijms22042190] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 02/12/2021] [Accepted: 02/18/2021] [Indexed: 02/07/2023] Open
Abstract
EPHA2 is a transmembrane tyrosine kinase receptor that, when disrupted, causes congenital and age-related cataracts. Cat-Map reports 22 pathogenic EPHA2 variants associated with congenital cataracts, variable microcornea, and lenticonus, but no previous association with microphthalmia (small, underdeveloped eye, ≥2 standard deviations below normal axial length). Microphthalmia arises from ocular maldevelopment with >90 monogenic causes, and can include a complex ocular phenotype. In this paper, we report two pathogenic EPHA2 variants in unrelated families presenting with bilateral microphthalmia and congenital cataracts. Whole genome sequencing through the 100,000 Genomes Project and cataract-related targeted gene panel testing identified autosomal dominant heterozygous mutations segregating with the disease: (i) missense c.1751C>T, p.(Pro584Leu) and (ii) splice site c.2826-9G>A. To functionally validate pathogenicity, morpholino knockdown of epha2a/epha2b in zebrafish resulted in significantly reduced eye size ± cataract formation. Misexpression of N-cadherin and retained fibre cell nuclei were observed in the developing lens of the epha2b knockdown morphant fish by 3 days post-fertilisation, which indicated a putative mechanism for microphthalmia pathogenesis through disruption of cadherin-mediated adherens junctions, preventing lens maturation and the critical signals stimulating eye growth. This study demonstrates a novel association of EPHA2 with microphthalmia, suggesting further analysis of pathogenic variants in unsolved microphthalmia cohorts may increase molecular diagnostic rates.
Collapse
Affiliation(s)
- Philippa Harding
- Institute of Ophthalmology, University College London, London EC1V 9EL, UK; (P.H.); (M.T.); (N.O.)
| | - Maria Toms
- Institute of Ophthalmology, University College London, London EC1V 9EL, UK; (P.H.); (M.T.); (N.O.)
- The Francis Crick Institute, London NW1 1AT, UK
| | - Elena Schiff
- Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK; (E.S.); (S.B.)
| | - Nicholas Owen
- Institute of Ophthalmology, University College London, London EC1V 9EL, UK; (P.H.); (M.T.); (N.O.)
| | - Suzannah Bell
- Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK; (E.S.); (S.B.)
| | - Ian Christopher Lloyd
- Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK;
- Manchester Academic Health Sciences Centre, University of Manchester, Manchester, M13 9PT, UK
- Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK
| | - Mariya Moosajee
- Institute of Ophthalmology, University College London, London EC1V 9EL, UK; (P.H.); (M.T.); (N.O.)
- The Francis Crick Institute, London NW1 1AT, UK
- Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK; (E.S.); (S.B.)
- Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK
| |
Collapse
|
|
18
|
Changal N, Khandekar RB. Eye Conformers as Socket Expanders in Children: Experience at a Tertiary Eye Hospital in Central Saudi Arabia. Cureus 2021; 13:e13465. [PMID: 33777554 PMCID: PMC7986163 DOI: 10.7759/cureus.13465] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Purpose To share our experience with pediatric orbital expansion using eye conformers for anophthalmia and microphthalmia and parental feedback on outcomes. Methods Cases of congenital anophthalmia and severe microphthalmia were managed with eye conformers for orbital expansion and formation of lid fornices at the anaplastology clinic of King Khaled Eye Specialist Hospital, Saudi Arabia. Data were collected on the globe adaptation process and the perceived achievements by the parents at different follow-up visits. Parental feedback was collected on their acceptance of eye conformer use to address anophthalmia and microphthalmia. Results The anophthalmia/microphthalmia annual prevalence was 1.7 per 10,000 live births in Saudi Arabia. Of the 45 sockets treated for orbital expansion since 2014, 15 children were managed by using eye conformers. Six children had a bilateral birth defect. Severe microphthalmia was in seven children while eight children had anophthalmos. At the first visit, small eye conformers (nine), stem eye conformer (four), symblepharon ring (one), and hydrogel eye conformer (one) were fitted. After multiple visits and follow-ups, at the two-year follow-up, seven (46.7%) children were fitted while three (20%) were under the process of prosthesis fitting, as volume expansion was satisfactory. Parents of these children replied that they prefer this method over others and would recommend others to follow the same. Conclusions Orbital expansion and lid fornices formation by using an eye conformer is effective, easy, and acceptable to parents. It can be initiated in the early months of a child's life.
Collapse
Affiliation(s)
- Nusrat Changal
- Oculoplasty/Anaplastology Clinic, King Khaled Eye Specialist Hospital, Riyadh, SAU
| | - Rajiv B Khandekar
- Epidemiology and Public Health, King Khalid Eye Specialist Hospital, Riyadh, SAU.,Ophthalmology, Faculty of Medicine, University of British Columbia, Vancouver, CAN
| |
Collapse
|
|
19
|
Harding P, Cunha DL, Moosajee M. Animal and cellular models of microphthalmia. THERAPEUTIC ADVANCES IN RARE DISEASE 2021; 2:2633004021997447. [PMID: 37181112 PMCID: PMC10032472 DOI: 10.1177/2633004021997447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Accepted: 02/02/2021] [Indexed: 05/16/2023]
Abstract
Microphthalmia is a rare developmental eye disorder affecting 1 in 7000 births. It is defined as a small (axial length ⩾2 standard deviations below the age-adjusted mean) underdeveloped eye, caused by disruption of ocular development through genetic or environmental factors in the first trimester of pregnancy. Clinical phenotypic heterogeneity exists amongst patients with varying levels of severity, and associated ocular and systemic features. Up to 11% of blind children are reported to have microphthalmia, yet currently no treatments are available. By identifying the aetiology of microphthalmia and understanding how the mechanisms of eye development are disrupted, we can gain a better understanding of the pathogenesis. Animal models, mainly mouse, zebrafish and Xenopus, have provided extensive information on the genetic regulation of oculogenesis, and how perturbation of these pathways leads to microphthalmia. However, differences exist between species, hence cellular models, such as patient-derived induced pluripotent stem cell (iPSC) optic vesicles, are now being used to provide greater insights into the human disease process. Progress in 3D cellular modelling techniques has enhanced the ability of researchers to study interactions of different cell types during eye development. Through improved molecular knowledge of microphthalmia, preventative or postnatal therapies may be developed, together with establishing genotype-phenotype correlations in order to provide patients with the appropriate prognosis, multidisciplinary care and informed genetic counselling. This review summarises some key discoveries from animal and cellular models of microphthalmia and discusses how innovative new models can be used to further our understanding in the future. Plain language summary Animal and Cellular Models of the Eye Disorder, Microphthalmia (Small Eye) Microphthalmia, meaning a small, underdeveloped eye, is a rare disorder that children are born with. Genetic changes or variations in the environment during the first 3 months of pregnancy can disrupt early development of the eye, resulting in microphthalmia. Up to 11% of blind children have microphthalmia, yet currently no treatments are available. By understanding the genes necessary for eye development, we can determine how disruption by genetic changes or environmental factors can cause this condition. This helps us understand why microphthalmia occurs, and ensure patients are provided with the appropriate clinical care and genetic counselling advice. Additionally, by understanding the causes of microphthalmia, researchers can develop treatments to prevent or reduce the severity of this condition. Animal models, particularly mice, zebrafish and frogs, which can also develop small eyes due to the same genetic/environmental changes, have helped us understand the genes which are important for eye development and can cause birth eye defects when disrupted. Studying a patient's own cells grown in the laboratory can further help researchers understand how changes in genes affect their function. Both animal and cellular models can be used to develop and test new drugs, which could provide treatment options for patients living with microphthalmia. This review summarises the key discoveries from animal and cellular models of microphthalmia and discusses how innovative new models can be used to further our understanding in the future.
Collapse
Affiliation(s)
| | | | - Mariya Moosajee
- UCL Institute of Ophthalmology, 11-43 Bath
Street, London, EC1V 9EL, UK
- Moorfields Eye Hospital NHS Foundation Trust,
London, UK
- Great Ormond Street Hospital for Children NHS
Foundation Trust, London, UK
- The Francis Crick Institute, London, UK
| |
Collapse
|
|
20
|
Schraw JM, Benjamin RH, Scott DA, Brooks BP, Hufnagel RB, McLean SD, Northrup H, Langlois PH, Canfield MA, Scheuerle AE, Schaaf CP, Ray JW, Chen H, Swartz MD, Mitchell LE, Agopian AJ, Lupo PJ. A Comprehensive Assessment of Co-occurring Birth Defects among Infants with Non-Syndromic Anophthalmia or Microphthalmia. Ophthalmic Epidemiol 2020; 28:428-435. [PMID: 33345678 DOI: 10.1080/09286586.2020.1862244] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
PURPOSE Infants with anophthalmia or microphthalmia frequently have co-occurring birth defects. Nonetheless, there have been few investigations of birth defect patterns among these children. Such studies may identify novel multiple malformation syndromes, which could inform future research into the developmental processes that lead to anophthalmia/microphthalmia and assist physicians in determining whether further testing is appropriate. METHODS This study includes cases with anophthalmia/microphthalmia identified by the Texas Birth Defects Registry from 1999 to 2014 without clinical or chromosomal diagnoses of recognized syndromes. We calculated adjusted observed-to-expected ratios for two - through five-way birth defect combinations involving anophthalmia/microphthalmia to estimate whether these combinations co-occur more often than would be expected if they were independent. We report combinations observed in ≥5 cases. RESULTS We identified 653 eligible cases with anophthalmia/microphthalmia (514 [79%] with co-occurring birth defects), and 111 birth defect combinations, of which 44 were two-way combinations, 61 were three-way combinations, six were four-way combinations and none were five-way combinations. Combinations with the largest observed-to-expected ratios were those involving central nervous system (CNS) defects, head/neck defects, and orofacial clefts. We also observed multiple combinations involving cardiovascular and musculoskeletal defects. CONCLUSION Consistent with previous reports, we observed that a large proportion of children diagnosed with anophthalmia/microphthalmia have co-occurring birth defects. While some of these defects may be part of a sequence involving anophthalmia/microphthalmia (e.g., CNS defects), other combinations could point to as yet undescribed susceptibility patterns (e.g., musculoskeletal defects). Data from population-based birth defect registries may be useful for accelerating the discovery of previously uncharacterized malformation syndromes.
Collapse
Affiliation(s)
- Jeremy M Schraw
- Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, Texas.,Department of Pediatrics, Center for Epidemiology and Population Health, Baylor College of Medicine, Houston, Texas
| | - Renata H Benjamin
- Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, Texas
| | - Daryl A Scott
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.,Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas
| | - Brian P Brooks
- Ophthalmic Genetics & Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, Maryland
| | - Robert B Hufnagel
- Ophthalmic Genetics & Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, Maryland
| | - Scott D McLean
- Clinical Genetics Section, The Children's Hospital of San Antonio, San Antonio, Texas
| | - Hope Northrup
- Department of Pediatrics, Division of Medical Genetics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas
| | - Peter H Langlois
- Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Austin, TX.,Texas Department of State Health Services, Birth Defects Epidemiology and Surveillance Branch, Austin, Texas
| | - Mark A Canfield
- Texas Department of State Health Services, Birth Defects Epidemiology and Surveillance Branch, Austin, Texas
| | - Angela E Scheuerle
- Department of Pediatrics, Division of Genetics and Metabolism, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Christian P Schaaf
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.,Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, Texas.,Institute of Human Genetics, Heidelberg University, Heidelberg, Germany
| | - Joseph W Ray
- Department of Pediatrics, Division of Medical Genetics and Metabolism, University of Texas Medical Branch, Galveston, Texas
| | - Han Chen
- Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, Texas.,Center for Precision Health, UTHealth School of Biomedical Informatics, Houston, Texas
| | - Michael D Swartz
- Department of Biostatistics and Data Science, UTHealth School of Public Health, Houston, Texas
| | - Laura E Mitchell
- Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, Texas
| | - A J Agopian
- Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, Texas
| | - Philip J Lupo
- Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, Texas.,Department of Pediatrics, Center for Epidemiology and Population Health, Baylor College of Medicine, Houston, Texas
| |
Collapse
|
|
21
|
Kougou Ntoutoume AR, Mekyna S, Assila S, Amazouzi A, Cherkaoui O. [Isolated congenital anophthalmia and microphthalmia: Report of 3 cases]. J Fr Ophtalmol 2020; 44:e75-e77. [PMID: 33341290 DOI: 10.1016/j.jfo.2020.04.053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Accepted: 04/17/2020] [Indexed: 11/17/2022]
Affiliation(s)
- A R Kougou Ntoutoume
- Faculté de médecine et de pharmacie, université Mohammed V, service ophtalmologie A, CHU Ibn Sina, hôpital des spécialités de Rabat, quartier Souissi, Rabat, Maroc.
| | - S Mekyna
- Faculté de médecine et de pharmacie, université Mohammed V, service ophtalmologie A, CHU Ibn Sina, hôpital des spécialités de Rabat, quartier Souissi, Rabat, Maroc
| | - S Assila
- Faculté de médecine et de pharmacie, université Mohammed V, service ophtalmologie A, CHU Ibn Sina, hôpital des spécialités de Rabat, quartier Souissi, Rabat, Maroc
| | - A Amazouzi
- Faculté de médecine et de pharmacie, université Mohammed V, service ophtalmologie A, CHU Ibn Sina, hôpital des spécialités de Rabat, quartier Souissi, Rabat, Maroc
| | - O Cherkaoui
- Faculté de médecine et de pharmacie, université Mohammed V, service ophtalmologie A, CHU Ibn Sina, hôpital des spécialités de Rabat, quartier Souissi, Rabat, Maroc
| |
Collapse
|
|
22
|
Taha Najim R, Topa A, Jugård Y, Casslén B, Odersjö M, Andersson Grönlund M. Children and young adults with anophthalmia and microphthalmia: Diagnosis and Management. Acta Ophthalmol 2020; 98:848-858. [PMID: 32436650 DOI: 10.1111/aos.14427] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2019] [Accepted: 03/11/2020] [Indexed: 12/14/2022]
Abstract
PURPOSE Congenital anophthalmia (A) and microphthalmia (M) are rare developmental defects, which could be isolated or syndromic. Our objective was to describe a cohort of children and young adults with A/M treated with ocular prosthesis, emphasizing clinical features, diagnosis, treatment, and follow-up. METHODS Eighteen individuals (10 female) with unilateral A (n = 3) and M (n = 15) with a mean age of 9.5 years (range 0.8-31.8) and treated with ocular prosthesis were included. Data on medical history, clinical examinations and management of ocular prosthesis were collected. Genetic screening with microarray and whole-exome sequencing targeting 121 A/M-related genes was performed. RESULTS A/M appeared isolated (seven cases) or as part of a syndromic condition (11 cases). In 4/16 patients, mutations were detected in TFAP2A, CHD7, FOXE3 and BCOR-genes. In one patient, a possibly causal microdeletion 10q11 was shown. Associated ocular anomalies such as cataract and cysts were found in 16 (89%) of the A/M eyes, and in nine (50%) ophthalmological findings were found in the fellow eyes. The median ages at which the conformer and ocular prosthesis first were initiated were 7.8 months and 1.5 years. 16/17 patients fulfilled satisfactory orbital growth and cosmetic results when treated with ocular prosthesis from an early age. CONCLUSION Based upon our findings, a multidisciplinary approach, including genetic assessment, is necessary to cover all aspects of A/M. Imaging, ultrasound and visual evoked potentials should be included. Early management is crucial for the outcome, in terms of non-ocular findings, vision in the fellow eye, and for facial cosmetic development.
Collapse
Affiliation(s)
- Rezhna Taha Najim
- Department of Clinical Neuroscience Institute of Neuroscience and Physiology Sahlgrenska Academy University of Gothenburg Gothenburg Sweden
| | - Alexandra Topa
- Region Västra Götaland Department of Clinical Genetics and Genomics Sahlgrenska University Hospital Gothenburg Sweden
- Department of Laboratory Medicine Institute of Biomedicine Sahlgrenska Academy University of Gothenburg Gothenburg Sweden
| | - Ylva Jugård
- Region Västra Götaland Department of Ophthalmology Hospital of Södra Älvsborg Borås Sweden
| | - Beatrice Casslén
- Department of Clinical Neuroscience Institute of Neuroscience and Physiology Sahlgrenska Academy University of Gothenburg Gothenburg Sweden
| | - Marie Odersjö
- Region Västra Götaland Department of Otolaryngology Sahlgrenska University Hospital Gothenburg Sweden
| | - Marita Andersson Grönlund
- Department of Clinical Neuroscience Institute of Neuroscience and Physiology Sahlgrenska Academy University of Gothenburg Gothenburg Sweden
- Region Västra Götaland Department of Ophthalmology Sahlgrenska University Hospital Mölndal Sweden
| |
Collapse
|
|
23
|
Casslén B, Jugård Y, Taha Najim R, Odersjö M, Topa A, Andersson Grönlund M. Visual function and quality of life in children and adolescents with anophthalmia and microphthalmia treated with ocular prosthesis. Acta Ophthalmol 2020; 98:662-670. [PMID: 32356375 DOI: 10.1111/aos.14424] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Accepted: 03/09/2020] [Indexed: 12/12/2022]
Abstract
PURPOSE To evaluate health-related quality of life (HR-QoL), vision-related (VR-)QoL and perceptual visual dysfunction (PVD) among individuals with anophthalmia (A) and microphthalmia (M) treated with ocular prosthesis. METHODS The study comprised 15 individuals (mean age 6.6 years; range 1.7-14.1) with unilateral A or M. Three validated instruments measuring HR-QoL and VR-QoL were used: The Pediatric QoL Inventory (PedsQL), consisting of physical and psychosocial self-report and parent-proxy report (2-18 years); Children's Visual Function Questionnaire (CVFQ); and Effects of Youngsters' Eyesight on Quality of Life (EYE-Q). Perceptual visual dysfunctions (PVDs) were assessed by history taking according to a specific protocol. RESULTS A/M children and their parents showed low HR-QoL scores (PedsQL total score: 66.3; 69.6) compared with controls (83.0; 87.61) (p = 0.0035 and <0.0001, respectively, unpaired t-test). No differences were found between A/M children and parents, but parents tended to underestimate their children's emotional state. A/M children with subnormal visual acuity (VA) for age scored lower in physical health compared with A/M children with normal VA (p = 0.03, Mann-Whitney U-test). No significant VR-QoL differences between A/M children and references or between A/M children with subnormal or normal VA for age were found. More A/M children than controls exhibited PVDs in ≥1 area (7/11 versus 4/118; p < 0.0001, Fisher's exact test). CONCLUSION A/M individuals show poor HR-QoL and increased PVDs. No difference in QoL was found between children and parents, though the children tended to score lower in emotional well-being. A/M children with subnormal VA showed lower physical health score. These problems indicate the necessity of a thorough multidisciplinary assessment and follow-up of children with A/M.
Collapse
Affiliation(s)
- Beatrice Casslén
- Department of Clinical Neuroscience Institute of Neuroscience and Physiology Sahlgrenska Academy University of Gothenburg Gothenburg Sweden
| | - Ylva Jugård
- Department of Ophthalmology Södra Älvsborg Hospital Region Västra Götaland Borås Sweden
| | - Rezhna Taha Najim
- Department of Clinical Neuroscience Institute of Neuroscience and Physiology Sahlgrenska Academy University of Gothenburg Gothenburg Sweden
| | - Marie Odersjö
- Department of Otolaryngology Sahlgrenska University Hospital Region Västra Götaland Gothenburg Sweden
| | - Alexandra Topa
- Department of Clinical Genetics and Genomics Sahlgrenska University Hospital Region Västra Götaland Gothenburg Sweden
- Department of Laboratory Medicine Institute of Biomedicine Sahlgrenska Academy University of Gothenburg Gothenburg Sweden
| | - Marita Andersson Grönlund
- Department of Clinical Neuroscience Institute of Neuroscience and Physiology Sahlgrenska Academy University of Gothenburg Gothenburg Sweden
- Department of Ophthalmology Sahlgrenska University Hospital Region Västra Götaland Mölndal Sweden
| |
Collapse
|
|
24
|
Harding P, Brooks BP, FitzPatrick D, Moosajee M. Anophthalmia including next-generation sequencing-based approaches. Eur J Hum Genet 2020; 28:388-398. [PMID: 31358957 PMCID: PMC7029013 DOI: 10.1038/s41431-019-0479-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Revised: 06/06/2019] [Accepted: 07/16/2019] [Indexed: 11/09/2022] Open
Abstract
Name of the disease (synonyms) See Table 1, Column 1-"Name of disease" and Column 2-"Alternative names". OMIM# of the disease See Table 1, Column 3-"OMIM# of the disease". Name of the analysed genes or DNA/chromosome segments and OMIM# of the gene(s) Core genes (irrespective of being tested by Sanger sequencing or next-generation sequencing): See Table 1, Column 4-"Cytogenetic location", Column 5-"Associated gene(s)" and Column 6-"OMIM# of associated gene(s)". Additional genes (if tested by next-generation sequencing, including Whole exome/genome sequencing and panel sequencing): See Table 2, Column 1-"Gene", Column 2-"Alternative names", Column 3-"OMIM# of gene" and Column 4-"Cytogenetic location". Review of the analytical and clinical validity as well as of the clinical utility of DNA-based testing for mutations in the gene(s) in diagnostic, predictive and prenatal settings, and for risk assessment in relatives.
Collapse
Affiliation(s)
| | - Brian P Brooks
- Ophthalmic Genetics & Visual Function Branch, National Eye Institute, Bethesda, MD, USA
| | | | - Mariya Moosajee
- UCL Institute of Ophthalmology, London, UK. .,Moorfields Eye Hospital NHS Foundation Trust, London, UK. .,Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
| |
Collapse
|
|
25
|
Calvas P, Traboulsi EI, Ragge N. Through the looking glass: eye anomalies in the age of molecular science. Hum Genet 2019; 138:795-798. [PMID: 31392423 DOI: 10.1007/s00439-019-02056-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Accepted: 08/01/2019] [Indexed: 11/29/2022]
Affiliation(s)
- Patrick Calvas
- INSERM U1056, Centre de Référence des Anomalies Rares en Génétique Ophtalmologique, Service de Génétique Médicale, Centre Hospitalier Universitaire de Toulouse, Université de Toulouse, Toulouse, France
| | - Elias I Traboulsi
- Center for Genetic Eye Diseases/i32, Cole Eye Institute, The Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, 44195, USA
| | - Nicola Ragge
- Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, OX3 0BP, UK. .,West Midlands Regional Clinical Genetics Service and Birmingham Health Partners, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, B15 2TG, UK.
| |
Collapse
|
|
26
|
Genetics of anophthalmia and microphthalmia. Part 1: Non-syndromic anophthalmia/microphthalmia. Hum Genet 2019; 138:799-830. [PMID: 30762128 DOI: 10.1007/s00439-019-01977-y] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Accepted: 01/30/2019] [Indexed: 12/22/2022]
Abstract
Eye formation is the result of coordinated induction and differentiation processes during embryogenesis. Disruption of any one of these events has the potential to cause ocular growth and structural defects, such as anophthalmia and microphthalmia (A/M). A/M can be isolated or occur with systemic anomalies, when they may form part of a recognizable syndrome. Their etiology includes genetic and environmental factors; several hundred genes involved in ocular development have been identified in humans or animal models. In humans, around 30 genes have been repeatedly implicated in A/M families, although many other genes have been described in single cases or families, and some genetic syndromes include eye anomalies occasionally as part of a wider phenotype. As a result of this broad genetic heterogeneity, with one or two notable exceptions, each gene explains only a small percentage of cases. Given the overlapping phenotypes, these genes can be most efficiently tested on panels or by whole exome/genome sequencing for the purposes of molecular diagnosis. However, despite whole exome/genome testing more than half of patients currently remain without a molecular diagnosis. The proportion of undiagnosed cases is even higher in those individuals with unilateral or milder phenotypes. Furthermore, even when a strong gene candidate is available for a patient, issues of incomplete penetrance and germinal mosaicism make diagnosis and genetic counseling challenging. In this review, we present the main genes implicated in non-syndromic human A/M phenotypes and, for practical purposes, classify them according to the most frequent or predominant phenotype each is associated with. Our intention is that this will allow clinicians to rank and prioritize their molecular analyses and interpretations according to the phenotypes of their patients.
Collapse
|
|
27
|
Sheth KR, Kovar E, White JT, Chambers TM, Peckham-Gregory EC, O'Neill M, Langlois PH, Seth A, Scheurer ME, Lupo PJ, Jorgez CJ. Hypospadias risk is increased with maternal residential exposure to hormonally active hazardous air pollutants. Birth Defects Res 2019; 111:345-352. [PMID: 30694020 DOI: 10.1002/bdr2.1461] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2018] [Revised: 11/19/2018] [Accepted: 12/28/2018] [Indexed: 11/12/2022]
Abstract
BACKGROUND With the increasing birth prevalence of hypospadias, there is growing concern for pollutant exposure interfering with normal penile development. We assess the association between hypospadias and hormonally active hazardous air pollutants (HAHAPs) through a nationwide database of hazardous air pollutants and the Texas Birth Defects Registry (TBDR). METHODS Using the TBDR, we identified 8,981 nonsyndromic isolated hypospadias cases from 1999 to 2008. Birth certificate controls were matched for birth year at a 10:1 ratio to cases. Estimated HAHAP concentrations from the 2005 U.S. EPA National-Scale Air Toxics Assessment were used to assign exposure based on maternal residence at birth. Exposure levels were categorized as quintiles based on the distribution in controls. Logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI) for each increasing exposure category of selected HAHAPs. RESULTS Of the 10 HAHAPs studied, seven were significantly associated with hypospadias risk. The HAHAP that was most strongly associated with hypospadias was phenol, which was associated with risk in all groups except the high exposure group. Cumulative HAHAP exposure demonstrated a modest increase in hypospadias risk (OR 1.15, 95% CI: 1.07-1.24, p < 0.001) in the medium and medium-high quintiles. CONCLUSIONS While maternal exposure to some HAHAPs was significantly associated with the risk of hypospadias in male offspring, the effects were modest, and no dose-response effects were observed. Future work should employ biomarkers of exposure to better delineate the relationship.
Collapse
Affiliation(s)
- Kunj R Sheth
- Scott Department of Urology, Baylor College of Medicine, Houston, Texas.,Division of Pediatric Urology, Department of Surgery, Texas Children's Hospital, Houston, Texas.,Center for Reproductive Medicine, Baylor College of Medicine, Houston, Texas
| | - Erin Kovar
- Section of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas
| | - Jeffrey T White
- Scott Department of Urology, Baylor College of Medicine, Houston, Texas.,Division of Pediatric Urology, Department of Surgery, Texas Children's Hospital, Houston, Texas.,Center for Reproductive Medicine, Baylor College of Medicine, Houston, Texas
| | - Tiffany M Chambers
- Section of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas
| | - Erin C Peckham-Gregory
- Section of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.,Department of Pediatrics, Texas Children's Hospital, Houston, Texas
| | - Marisol O'Neill
- Center for Reproductive Medicine, Baylor College of Medicine, Houston, Texas.,Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas
| | - Peter H Langlois
- Birth Defects Epidemiology and Surveillance Branch, Texas Department of State Health Services, Austin, Texas
| | - Abhishek Seth
- Scott Department of Urology, Baylor College of Medicine, Houston, Texas.,Division of Pediatric Urology, Department of Surgery, Texas Children's Hospital, Houston, Texas.,Center for Reproductive Medicine, Baylor College of Medicine, Houston, Texas
| | - Michael E Scheurer
- Section of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.,Department of Pediatrics, Texas Children's Hospital, Houston, Texas
| | - Philip J Lupo
- Section of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.,Department of Pediatrics, Texas Children's Hospital, Houston, Texas
| | - Carolina J Jorgez
- Scott Department of Urology, Baylor College of Medicine, Houston, Texas.,Division of Pediatric Urology, Department of Surgery, Texas Children's Hospital, Houston, Texas.,Center for Reproductive Medicine, Baylor College of Medicine, Houston, Texas
| |
Collapse
|
|
28
|
Stallings EB, Isenburg JL, Mai CT, Liberman RF, Moore CA, Canfield MA, Salemi JL, Kirby RS, Short TD, Nembhard WN, Forestieri NE, Heinke D, Alverson CJ, Romitti PA, Huynh MP, Denson LE, Judson EM, Lupo PJ. Population-based birth defects data in the United States, 2011-2015: A focus on eye and ear defects. Birth Defects Res 2018; 110:1478-1486. [PMID: 30444307 DOI: 10.1002/bdr2.1413] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2018] [Revised: 09/25/2018] [Accepted: 09/26/2018] [Indexed: 11/07/2022]
Abstract
BACKGROUND/OBJECTIVES In this data brief, we examine major eye and ear anomalies (anophthalmia/microphthalmia, anotia/microtia, and congenital cataract) for a recent 5-year birth cohort using data from 30 population-based birth defects surveillance programs in the United States. METHODS As a special call for data for the 2018 NBDPN Annual Report, state programs reported expanded data on eye/ear anomalies for birth years 2011-2015. We calculated the combined overall prevalence (per 10,000 live births) and 95% confidence intervals (CI), for the three anomalies as well as by maternal age, maternal race/ethnicity, infant sex, laterality, presence/absence of other major birth defects, and case ascertainment methodology utilized by the program (active vs. passive). RESULTS The overall prevalence estimate (per 10,000 live births) was 1.5 (95% CI: 1.4-1.5) for anophthalmia/microphthalmia, 1.5 (95% CI: 1.4-1.6) for congenital cataract, and 1.8 (95% CI: 1.7-1.8) for anotia/microtia. Congenital cataract prevalence varied little by maternal race/ethnicity, infant sex, or case ascertainment methodology; prevalence differences were more apparent across strata for anophthalmia/microphthalmia and anotia/microtia. Prevalence among active vs. passive ascertainment programs was 50% higher for anophthalmia/microphthalmia (1.9 vs. 1.2) and two-fold higher for anotia/microtia (2.6 vs. 1.2). Anophthalmia/microphthalmia was more likely than other conditions to co-occur with other birth defects. All conditions were more frequent among older mothers (40+ years). CONCLUSIONS This data brief provides recent prevalence estimates for anophthalmia/microphthalmia, congenital cataract, and anotia/microtia that address a data gap by examining pooled data from 30 population-based surveillance systems, covering a five-year birth cohort of about 12.4 million births.
Collapse
Affiliation(s)
- Erin B Stallings
- National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia.,Carter Consulting, Incorporated, Atlanta, Georgia
| | - Jennifer L Isenburg
- National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Cara T Mai
- National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Rebecca F Liberman
- Massachusetts Department of Public Health, Center for Birth Defects Research and Prevention, Boston, Massachusetts
| | - Cynthia A Moore
- National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Mark A Canfield
- Texas Department of State Health Services, Birth Defects Epidemiology and Surveillance Branch, Austin, Texas
| | - Jason L Salemi
- Department of Family and Community Medicine, Baylor College of Medicine, Houston, Texas
| | - Russell S Kirby
- Department of Community and Family Health, College of Public Health, University of South Florida, Tampa, Florida
| | - Tyiesha D Short
- National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia.,Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee
| | - Wendy N Nembhard
- Arkansas Center for Birth Defects Research and Prevention, the Arkansas Children's Research Institute and the University of Arkansas for Medical Sciences, Department of Epidemiology, Little Rock, Arkansas
| | - Nina E Forestieri
- Division of Public Health, North Carolina Department of Health and Human Services, Raleigh, North Carolina
| | - Dominique Heinke
- Massachusetts Department of Public Health, Center for Birth Defects Research and Prevention, Boston, Massachusetts
| | - C J Alverson
- National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Paul A Romitti
- College of Public Health, University of Iowa, Iowa City, Iowa
| | - My-Phuong Huynh
- Utah Birth Defect Network, Utah Department of Health, Salt Lake City, Utah
| | - Lindsay E Denson
- Oklahoma Birth Defects Registry, Oklahoma State Department of Health, Oklahoma City, Oklahoma
| | - Emily M Judson
- National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia.,Carter Consulting, Incorporated, Atlanta, Georgia
| | - Philip J Lupo
- Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, Texas
| | | |
Collapse
|