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Journal of Ayub Medical College,... 2019A foetus affected by a congenital rubella infection can develop congenital rubella syndrome (CRS). Aniridia is the absence of iris, rarely been described in literature...
A foetus affected by a congenital rubella infection can develop congenital rubella syndrome (CRS). Aniridia is the absence of iris, rarely been described in literature in association with CRS, can easily be overlooked, leading to complications e.g. glaucoma and blindness later in life. We report a case of a neonate with CRS and aniridia presenting at a tertiary care hospital.
Topics: Aniridia; Female; Humans; Infant, Newborn; Rubella Syndrome, Congenital
PubMed: 30868799
DOI: No ID Found -
Der Ophthalmologe : Zeitschrift Der... Apr 2022
Topics: Aniridia; Eye Injuries; Humans; Iris; Lenses, Intraocular
PubMed: 33779827
DOI: 10.1007/s00347-021-01367-8 -
Journal of Medical Genetics Apr 2021BackgroundAniridia is a severe autosomal dominant panocular disorder associated with pathogenic sequence variants of the gene or 11p13 chromosomal aberrations...
BackgroundAniridia is a severe autosomal dominant panocular disorder associated with pathogenic sequence variants of the gene or 11p13 chromosomal aberrations encompassing the coding and/or regulatory regions of the gene in a heterozygous state. Patients with aniridia display several ocular anomalies including foveal hypoplasia, cataract, keratopathy, and glaucoma, which can vary in severity and combination.MethodsA cohort of 155 patients from 125 unrelated families with identified point pathogenic variants (118 patients) or large chromosomal 11p13 deletions (37 patients) was analyzed. Genetic causes were divided into 6 types. The occurrence of 6 aniridic eye anomalies was analyzed. Fisher's exact test was applied for 2×2 contingency tables assigning numbers of patients with/without each sign and each type of the variants or 11p13 deletions with Benjamini-Hochberg correction. The age of patients with different types of mutation did not differ.ResultsPatients with 3'--regulatory region deletions had a milder aniridia phenotype without keratopathy, nystagmus, or foveal hypoplasia. The phenotypes of the patients with other rearrangements involving 11p13 do not significantly differ from those associated with point pathogenic variants in the gene. Missense mutations and genetic variants disrupting splicing are associated with a severe aniridia phenotype and resemble loss-of-function mutations. It is particularly important that in all examined patients, mutations were found to be associated with multiple eye malformations. The age of patients with keratopathy, cataract, and glaucoma was significantly higher than the age of patients without these signs.ConclusionWe got clear statistically significant genotype-phenotype correlations in congenital aniridia and evident that aniridia severity indeed had worsened with age.
Topics: Adolescent; Adult; Aniridia; Cataract; Child; Child, Preschool; Eye Abnormalities; Female; Genetic Association Studies; Genetic Predisposition to Disease; Glaucoma; Humans; Male; Mutation, Missense; PAX6 Transcription Factor; Pedigree; Young Adult
PubMed: 32467297
DOI: 10.1136/jmedgenet-2019-106172 -
Journal of AAPOS : the Official... Aug 2023To report on the incidence, characteristics, and treatment of glaucoma in association with aniridia in a population of Egyptian children.
PURPOSE
To report on the incidence, characteristics, and treatment of glaucoma in association with aniridia in a population of Egyptian children.
METHODS
A retrospective chart review was conducted of children (<18 years of age) presenting with aniridia between 2007 and 2022. Diagnosis of glaucoma was based on cup:disk ratio (>0.3) and IOP (>16 mm Hg). Success of glaucoma surgery was defined as IOP ≤16 mm Hg and stable or regressing cup:disk ratio.
RESULTS
A total of 93 eyes of 47 children were included. The mean patient age at presentation was 41.2 ± 44.7 months. The mean intraocular pressure (IOP), corneal diameter, cup:disk ratio, and axial length on presentation were 16.4 ± 10.3 mm Hg, 11.4 ± 1.3 mm, 0.4 ± 0.3, and 22.43 ± 2.6 mm Hg. Of eyes with IOP and cup:disk ratio data at presentation, 23 (30%) were diagnosed with glaucoma. Fourteen eyes underwent surgery after presentation; follow-up data were available for half the remaining eyes. At the final follow-up, glaucoma was present in 20 eyes (49%). Glaucoma surgery was performed in 17 eyes, with a complete or qualified success rate of 82.4% at final follow-up, with 15 eyes having at least 12 months' follow-up.
CONCLUSIONS
In this study cohort, children with aniridia presented at around 3 years of age, with glaucoma at presentation in almost one-third of the cases.
Topics: Humans; Child; Child, Preschool; Retrospective Studies; Egypt; Glaucoma; Intraocular Pressure; Aniridia; Treatment Outcome; Follow-Up Studies; Trabeculectomy
PubMed: 37499898
DOI: 10.1016/j.jaapos.2023.06.005 -
American Journal of Ophthalmology Sep 2023This study aims to characterize foveal vasculature assessed by optical coherence tomography angiography (OCT-A) in congenital aniridia which is hallmarked by foveal...
PURPOSE
This study aims to characterize foveal vasculature assessed by optical coherence tomography angiography (OCT-A) in congenital aniridia which is hallmarked by foveal hypoplasia (FH).
DESIGN
Cross-sectional case-control analysis.
METHODS
At the National Referral Center for congenital aniridia, patients with confirmed PAX6-related aniridia and FH diagnosed on spectral-domain OCT (SD-OCT) with available OCT-A and matched control subjects were included. OCT-A was performed in patients with aniridia and control subjects. Foveal avascular zone (FAZ) and vessel density (VD) were collected. VD in the foveal and parafoveal areas at the level of the superficial and deep capillary plexi (SCP and DCP, respectively) were compared between the 2 groups. In patients with congenital aniridia, correlation between VD and the grading of FH was assessed.
RESULTS
Among 230 patients with confirmed PAX6-related aniridia, high-quality macular B-scans and OCT-A were available in 10 patients. On the foveal area, mean VD was higher in aniridia patients (41.10%, n = 10) than in control subjects (22.65%, n = 10) at the level of the SCP and the DCP (P = .0020 and P = .0273, respectively). On the parafoveal area, mean VD was lower in patients with aniridia (42.34%, n = 10) than in healthy subjects (49.24%, n = 10) at the level of both plexi (P = .0098 and P = .0371, respectively). In patients with congenital aniridia, a positive correlation was found between the grading of FH and the foveal VD at the SCP (r = 0.77, P = .0106).
CONCLUSIONS
Vasculature is altered in PAX6-related congenital aniridia, higher in foveal and lower in parafoveal areas, especially when FH is severe, which is consistent with the concept that the absence of retinal blood vessels is essential for foveal pit development.
Topics: Humans; Tomography, Optical Coherence; Fluorescein Angiography; Cross-Sectional Studies; Macula Lutea; Retinal Vessels; Aniridia; Vision Disorders
PubMed: 37059316
DOI: 10.1016/j.ajo.2023.04.004 -
Internal Medicine (Tokyo, Japan) 2014We herein report the case of a woman with aniridia and with a heterozygous PAX6 mutation. Pax6 is a transcription factor involved in the development of several organs,... (Review)
Review
We herein report the case of a woman with aniridia and with a heterozygous PAX6 mutation. Pax6 is a transcription factor involved in the development of several organs, including the eye, pancreas and pituitary. The patient had been diagnosed with aniridia in childhood and was found to have impaired glucose tolerance with a heterozygous PAX6 mutation 12 years prior to the current admission. Hormone stimulating tests revealed a slightly impaired pituitary function, including subtle hypogonadotropic hypogonadism and borderline growth hormone (GH) deficiency. The present case is the first report of a slightly impaired pituitary function in an aniridia patient with a heterozygous PAX6 mutation.
Topics: Adult; Aniridia; Eye Proteins; Female; Heterozygote; Homeodomain Proteins; Humans; Hypopituitarism; Mutation; PAX6 Transcription Factor; Paired Box Transcription Factors; Pilot Projects; Pituitary Gland; Repressor Proteins
PubMed: 24390526
DOI: 10.2169/internalmedicine.53.1184 -
Archivos de La Sociedad Espanola de... Apr 2013Aniridia is a panocular disorder which occurs in 1/50,000 to 1/100,000 live births and can appear either in isolated form or in the context of a syndrome. Isolated... (Review)
Review
INTRODUCTION
Aniridia is a panocular disorder which occurs in 1/50,000 to 1/100,000 live births and can appear either in isolated form or in the context of a syndrome. Isolated aniridia is inherited as an autosomal dominant condition and is caused by mutations of the PAX6 gene. A variety of techniques and methodologies within molecular genetics and cytogenetics are used to study these mutations.
OBJECTIVE
To identify the different aspects of this disease and to provide a guide for proper genetic diagnosis leading to improved clinical management of the disease.
DEVELOPMENT
Aniridia is an autosomal dominant disease that primarily affects the iris, though it can impact most of the ocular structures. The disease is mainly caused by mutations in the PAX6 gene located on chromosome 11p13 which encodes a transcription factor that is involved in the development of the eye. Genetic analysis of aniridia is complex and requires the use of both molecular genetics and cytogenetics techniques. These procedures are indicated in all cases of aniridia. It is important bear certain clinical and technical aspects in mind prior to starting analysis or providing genetic counseling for patients and their families.
CONCLUSIONS
The use of molecular genetic techniques in the genetic diagnosis of aniridia enables patients and their families to receive better clinical management.
Topics: Aniridia; Decision Trees; Humans; Practice Guidelines as Topic
PubMed: 23597644
DOI: 10.1016/j.oftal.2012.07.006 -
Human Genomics Jun 2023Haploinsufficiency of the transcription factor PAX6 is the main cause of congenital aniridia, a genetic disorder characterized by iris and foveal hypoplasia. 11p13...
BACKGROUND
Haploinsufficiency of the transcription factor PAX6 is the main cause of congenital aniridia, a genetic disorder characterized by iris and foveal hypoplasia. 11p13 microdeletions altering PAX6 or its downstream regulatory region (DRR) are present in about 25% of patients; however, only a few complex rearrangements have been described to date. Here, we performed nanopore-based whole-genome sequencing to assess the presence of cryptic structural variants (SVs) on the only two unsolved "PAX6-negative" cases from a cohort of 110 patients with congenital aniridia after unsuccessfully short-read sequencing approaches.
RESULTS
Long-read sequencing (LRS) unveiled balanced chromosomal rearrangements affecting the PAX6 locus at 11p13 in these two patients and allowed nucleotide-level breakpoint analysis. First, we identified a cryptic 4.9 Mb de novo inversion disrupting intron 7 of PAX6, further verified by targeted polymerase chain reaction amplification and sequencing and FISH-based cytogenetic analysis. Furthermore, LRS was decisive in correctly mapping a t(6;11) balanced translocation cytogenetically detected in a second proband with congenital aniridia and considered non-causal 15 years ago. LRS resolved that the breakpoint on chromosome 11 was indeed located at 11p13, disrupting the DNase I hypersensitive site 2 enhancer within the DRR of PAX6, 161 Kb from the causal gene. Patient-derived RNA expression analysis demonstrated PAX6 haploinsufficiency, thus supporting that the 11p13 breakpoint led to a positional effect by cleaving crucial enhancers for PAX6 transactivation. LRS analysis was also critical for mapping the exact breakpoint on chromosome 6 to the highly repetitive centromeric region at 6p11.1.
CONCLUSIONS
In both cases, the LRS-based identified SVs have been deemed the hidden pathogenic cause of congenital aniridia. Our study underscores the limitations of traditional short-read sequencing in uncovering pathogenic SVs affecting low-complexity regions of the genome and the value of LRS in providing insight into hidden sources of variation in rare genetic diseases.
Topics: Humans; Paired Box Transcription Factors; Homeodomain Proteins; Repressor Proteins; Aniridia; Chromosome Inversion; Mutation
PubMed: 37269011
DOI: 10.1186/s40246-023-00490-8 -
Der Ophthalmologe : Zeitschrift Der... Dec 2014
Topics: Aniridia; Eye Proteins; Genetic Predisposition to Disease; Homeodomain Proteins; Humans; PAX6 Transcription Factor; Paired Box Transcription Factors; Polymorphism, Single Nucleotide; Repressor Proteins
PubMed: 25475186
DOI: 10.1007/s00347-014-3058-4 -
Der Ophthalmologe : Zeitschrift Der... Feb 2022Three groups of iris prostheses can be distinguished for the surgical treatment of iris defects: (1) segmental iris implants, (2) combined iris diaphragm intraocular...
BACKGROUND
Three groups of iris prostheses can be distinguished for the surgical treatment of iris defects: (1) segmental iris implants, (2) combined iris diaphragm intraocular lenses (IOL) and (3) pure iris implants. Most iris reconstructions are accompanied by aphakia correction with secondary IOL implantation. Although the primary goal is to create a pupil and to improve glare perception, contrast sensitivity and visual acuity, the esthetic result is also a relevant component.
OBJECTIVE
Functional and esthetic results after replacement of an aniridia IOL implant with a custom-made artificial iris with IOL.
MATERIAL AND METHODS
In this retrospective study with seven eyes from seven patients, an iris diaphragm IOL (Morcher GmbH, Stuttgart, Germany) was exchanged for medical reasons (subluxation) against a custom-made artificial iris made of silicone (ArtificialIris, HumanOptics, Erlangen, Germany) in combination with a sutured IOL. The follow-up period was at least 3 months. Best corrected distance visual acuity (BCVA), endothelial cell count (ECC), complications, glare perception as well as esthetic outcome and patient satisfaction were evaluated.
RESULTS
The BCVA and ECC showed no statistically significant change between the preoperative and postoperative values (p > 0.05). There was a decentration of the iris IOL implant of 0.27 ± 0.19 mm three months postoperatively. On a visual analogue scale (VAS) from 1 to 10 (1 = not satisfied at all, 10 = extremely satisfied), satisfaction with the overall result was rated 8.6 ± 2.5. Subjective glare perception improved to 5.6 ± 3.5 and subjective esthetic impairment improved to 2.4 ± 2.0 on the VAS (1 = none, 10 = extremely strong). Postoperative complications included transient intraocular hypotonia in two eyes, intraocular pressure increase in two eyes, retinal detachment and transient vitreous hemorrhage in one eye each. Of the seven patients six would repeat the procedure.
CONCLUSION
Compared to a rigid aniridia IOL implant, replacement with a custom-made artificial iris in combination with an IOL provides not only a good functional result but simultaneously also an esthetically pleasing result.
Topics: Aniridia; Humans; Iris; Lens Implantation, Intraocular; Lenses, Intraocular; Retrospective Studies
PubMed: 34236489
DOI: 10.1007/s00347-021-01447-9