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Archivos de La Sociedad Espanola de... Nov 2021Congenital aniridia is a multisystemic genetic disease due to a mutation in PAX6 gene which severely affects the development and functionality of the human eyes. In... (Review)
Review
Congenital aniridia is a multisystemic genetic disease due to a mutation in PAX6 gene which severely affects the development and functionality of the human eyes. In patients affected by the mutation, aside from the absence or defects of iris tissue formation, abnormalities in position or opacities of the crystalline lens, macular hypoplasia, ocular surface disease is the main cause of visual loss and the deterioration of the quality of life of most patients. Limbal stem cell deficiency combined with tear film instability and secondary dry eye cause aniridic keratopathy which, in advanced stages, ends up in corneal opacification. In this paper, the actual knowledge about congenital aniridia keratopathy physiopathology and medical and surgical treatment options and their efficacy are discussed. Indications and results of topical treatments with artificial tears and blood-derivatives in its initial stages, and different surgical techniques as limbal stem cell transplantation, keratoplasty and keratoprostheses are reviewed. Finally, recent advances and results in regenerative medicine techniques with ex vivo stem cell cultivation or other types of cultivated cells are presented.
Topics: Aniridia; Cornea; Corneal Diseases; Corneal Transplantation; Humans; Quality of Life
PubMed: 34836585
DOI: 10.1016/j.oftale.2021.04.003 -
Current Opinion in Ophthalmology Sep 2017Aniridia is a rare and panocular disorder affecting most of the ocular structures which may have significant impact on vision. The purpose of this review is to describe... (Review)
Review
PURPOSE OF REVIEW
Aniridia is a rare and panocular disorder affecting most of the ocular structures which may have significant impact on vision. The purpose of this review is to describe the clinical features, genetics, and therapeutic options for this disease and to provide an update of current knowledge and latest research findings.
RECENT FINDINGS
Aside from the ocular features, a variety of associated systemic abnormalities, including hormonal, metabolic, gastrointestinal, genitourinary, and neurologic pathologies have been reported in children with aniridia. Although mutations in PAX6 are a major cause of aniridia, genetic defects in nearby genes, such as TRIM44 or ELP4, have also been reported to cause aniridia. Recent improvement in genetic testing technique will help more rapid and precise diagnosis for aniridia. A promising therapeutic approach called nonsense suppression therapy has been introduced and successfully used in an animal model.
SUMMARY
Aniridia is a challenging disease. The progressive nature of this condition and its potential complications require continuous and life-long ophthalmologic care. Genetic diagnosis for aniridia is important for establishing definitive molecular characterization as well as identifying individuals at high risk for Wilms tumor. Recent advancement in understanding the genetic pathogenesis of this disease offers promise for the approaches to treatment.
Topics: Aniridia; Diagnostic Techniques, Ophthalmological; Disease Management; Genetic Testing; Humans; Mutation; PAX6 Transcription Factor; Syndrome
PubMed: 28598868
DOI: 10.1097/ICU.0000000000000405 -
Experimental Eye Research Dec 2019Aniridia and Axenfeld-Rieger Syndrome are related, human ocular disorders that are typically inherited in an autosomal dominant manner. Both result from incorrect... (Review)
Review
Aniridia and Axenfeld-Rieger Syndrome are related, human ocular disorders that are typically inherited in an autosomal dominant manner. Both result from incorrect development of the eye and have, as their most serious consequences, elevated risk to develop the blinding condition glaucoma. This review will focus on describing the clinical presentations of Aniridia and Axenfeld-Rieger Syndrome as well as the molecular genetics and current and emerging therapies used to treat patients.
Topics: Abnormalities, Multiple; Aniridia; Anterior Eye Segment; Eye Abnormalities; Eye Diseases, Hereditary; Genotype; Homeodomain Proteins; Humans; Mutation
PubMed: 31560925
DOI: 10.1016/j.exer.2019.107815 -
The Ocular Surface Apr 2016Aniridia is a congenital pan-ocular disorder caused by haplo-insufficiency of Pax6, a crucial gene for proper development of the eye. Aniridia affects a range of eye... (Review)
Review
Aniridia is a congenital pan-ocular disorder caused by haplo-insufficiency of Pax6, a crucial gene for proper development of the eye. Aniridia affects a range of eye structures, including the cornea, iris, anterior chamber angle, lens, and fovea. The ocular surface, in particular, can be severely affected by a progressive pathology termed aniridia-associated keratopathy (AAK), markedly contributing to impaired vision. The purpose of this review is to provide an update of the current knowledge of the genetic, clinical, micro-morphological, and molecular aspects of AAK. We draw upon material presented in the literature and from our own observations in large aniridia cohorts. We summarize signs and symptoms of AAK, describe current options for management, and discuss the latest research findings that may lead to better diagnosis and new treatment or prevention strategies for this debilitating ocular surface condition.
Topics: Aniridia; Anterior Eye Segment; Cornea; Humans; Visual Acuity
PubMed: 26738798
DOI: 10.1016/j.jtos.2015.10.003 -
Arquivos de Neuro-psiquiatria Jun 2020
Topics: Aniridia; Cerebellar Ataxia; Humans; Intellectual Disability
PubMed: 32609195
DOI: 10.1590/0004-282X20200013 -
Archivos de La Sociedad Espanola de... Nov 2021
Topics: Aniridia; Humans; Ophthalmology; Visual Acuity
PubMed: 34836586
DOI: 10.1016/j.oftale.2021.08.001 -
Journal of Applied Genetics May 2018Aniridia is a rare, panocular disorder characterized by a variable degree of hypoplasia or the absence of iris tissue associated with additional ocular abnormalities. It... (Review)
Review
Aniridia is a rare, panocular disorder characterized by a variable degree of hypoplasia or the absence of iris tissue associated with additional ocular abnormalities. It is inherited in an autosomal dominant manner, with high penetrance and variable expression even within the same family. In most cases the disease is caused by haploinsufficiency truncating mutations in the PAX6 gene; however, in up to 30% of aniridia patients, disease results from chromosomal rearrangements at the 11p13 region. The aim of this review is to present the clinical and genetic aspects of the disease. Furthermore, we present a molecular diagnostic strategy in the aniridia patients. Recent improvement in the genetic diagnostic approach will precisely diagnosis aniridia patients, which is essential especially for children with aniridia in order to determine the risk of developing a Wilms tumor or neurodevelopmental disorder. Finally, based on the previous studies we describe the current knowledge and latest research findings in the topic of pathogenesis of aniridia and possible future treatment.
Topics: Aniridia; Genetic Testing; Humans; Mutation; PAX6 Transcription Factor
PubMed: 29460221
DOI: 10.1007/s13353-017-0426-1 -
Ophthalmology. Glaucoma 2021
Topics: Aniridia; Eye Abnormalities; Humans; Pupil Disorders
PubMed: 33771336
DOI: 10.1016/j.ogla.2020.12.004 -
Archivos de La Sociedad Espanola de... Nov 2021Aniridia is a panocular disease characterized by iris hypoplasia, accompanied by other ocular manifestations, with a high clinical variability and overlapping with... (Review)
Review
Aniridia is a panocular disease characterized by iris hypoplasia, accompanied by other ocular manifestations, with a high clinical variability and overlapping with different abnormalities of the anterior and posterior segment. This review focuses on the genetic features of this autosomal dominant pathology, which is caused by the haploinsufficiency of the PAX6 gene. Mutations causing premature stop codons are the most frequent among the wider mutational spectrum of PAX6, with more than 600 different mutations identified so far. Recent advances in next-generation sequencing (NGS) have increased the diagnostic yield in aniridia and contributed to elucidate new etiopathogenic mechanisms leading to PAX6 haploinsufficiency. Here, we also update good practices and recommendations to improve genetic testing and clinical management of aniridia using more cost-effective NGS analysis. Those new approaches also allow studying simultaneously both structural variants and point-mutations in PAX6 as well as other genes for differential diagnosis, simultaneously. Some patients with atypical phenotypes might present mutations in FOXC1 and PITX2, both genes causing a wide spectrum of anterior segment dysgenesis, or in ITPR1, which is responsible for a distinctive form of circumpupillary iris aplasia present in Gillespie syndrome, or other mutations in minor genes. Since aniridia can also associate extraocular anomalies, as it occurs in carriers of PAX6 and WT1 microdeletions leading to WAGR syndrome, genetic studies are crucial to assure a correct diagnosis and clinical management, besides allowing prenatal and preimplantational genetic testing in families.
Topics: Aniridia; Cerebellar Ataxia; Humans; Mutation; PAX6 Transcription Factor; WAGR Syndrome
PubMed: 34836588
DOI: 10.1016/j.oftale.2021.02.002 -
Indian Journal of Ophthalmology Jul 2022Congenital aniridia is a pan ocular disorder characterized by partial or total loss of iris tissue as the defining feature. Classic aniridia, however, has a spectrum of... (Review)
Review
Congenital aniridia is a pan ocular disorder characterized by partial or total loss of iris tissue as the defining feature. Classic aniridia, however, has a spectrum of ocular findings, including foveal hypoplasia, optic nerve hypoplasia, nystagmus, late-onset cataract, glaucoma, and keratopathy. The latter three are reasons for further visual compromise in such patients. This entity is often due to mutations in the PAX6 (Paired box protein Pax-6) gene. Recently, aniridia-like phenotypes have been reported due to non-PAX6 mutations as in PITX2, FOXC1, FOXD3, TRIM44, and CYP1B1 as well wherein there is an overlap of aniridia, such as iris defects with congenital glaucoma or anterior segment dysgenesis. In this review, we describe the various clinical features of classic aniridia, the comorbidities and their management, the mutation spectrum of the genes involved, genotype-phenotype correlation of PAX6 and non-PAX6 mutations, and the genetic testing plan. The various systemic associations and their implications in screening and genetic testing have been discussed. Finally, the future course of aniridia treatment in the form of drugs (such as ataluren) and targeted gene therapy has been discussed.
Topics: Aniridia; Eye Abnormalities; Glaucoma; Humans; Intracellular Signaling Peptides and Proteins; PAX6 Transcription Factor; Phenotype; Tripartite Motif Proteins
PubMed: 35791108
DOI: 10.4103/ijo.IJO_2255_21