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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 -
Journal of Clinical Medicine Sep 2023Childhood glaucoma is one of the most common causes of corneal opacity in childhood and is associated with various pathological corneal changes, including corneal...
BACKGROUND
Childhood glaucoma is one of the most common causes of corneal opacity in childhood and is associated with various pathological corneal changes, including corneal enlargement, corneal clouding, and edema. Congenital glaucoma (CG) may cause a decrease in vision outcomes due to corneal opacity or clouding, which is often associated with stimulus deprivation amblyopia. Therefore, to create a balance between preventing amblyopia and sustaining corneal clearance, patients with CG can be managed with early penetrating corneal transplantation surgery along with advanced glaucoma management.
AIM
To investigate the graft survival rate and factors affecting graft survival in patients with congenital glaucoma who underwent penetrating keratoplasty (PKP).
STUDY DESIGN
Cross-sectional.
MATERIALS AND METHODS
Patients with congenital glaucoma who underwent PKP were retrospectively evaluated. The associations between age, corneal diameter, presence of ocular comorbidities, concurrent ocular surgeries with corneal graft, and visual outcomes were assessed.
RESULTS
Among the 30 eyes enrolled in the study, 6 (20%) had aniridia, 6 (20%) had Axenfeld-Rieger syndrome, and 18 (60%) were diagnosed with primary congenital glaucoma. Graft survival rates were 66.6% and 63.33% at 12 and 24 months, respectively. At the end of the follow-up, the overall graft survival rate was 60%. Statistical significance was observed between patient age at the time of surgery and graft failure ( = 0.02). Graft failure was associated with a younger patient age. Functional vision was achieved in 53.3% of patients.
CONCLUSIONS
The management of congenital glaucoma and its corneal complications is a delicate issue that requires great effort. PKP in congenital glaucoma was moderately successful in the present study. To provide functional vision, PKP could be the treatment of choice.
PubMed: 37834920
DOI: 10.3390/jcm12196276 -
European Journal of Ophthalmology Sep 2022To determine the long-term outcomes of a cohort of complex patients with primary congenital glaucoma, aniridia and anterior segment dysgenesis.
AIM
To determine the long-term outcomes of a cohort of complex patients with primary congenital glaucoma, aniridia and anterior segment dysgenesis.
METHODS
Retrospective consecutive series between 1990-2021 in two UK tertiary centres: Guy's and St Thomas' NHS Foundation Trust and King's College Hospital NHS Foundation Trust. We recorded the number and types of surgical and laser treatments along with preoperative and postoperative data, including intraocular pressures (IOP) and anti-glaucoma medications.
RESULTS
A total of 41 eyes of 21 patients were included. Primary diagnoses were primary congenital glaucoma in 16 eyes (39.0%), aniridia in 14 eyes (34.2%), and anterior segment dysgenesis in 8 eyes (19.5%). Sixteen eyes (39.0%) had one or more glaucoma surgery or laser procedures for advanced glaucoma, and the long-term follow-up was 12.8 ± 3.6 years. There was a significant decrease in postoperative IOP (mmHg) at 3 months (16.5 ± 1.6; = 0.0067), 6 months (18.7 ± 2.1; = 0.0386), 12 months (18.6 ± 1.7; = 0.0229), 3 years (14.7 ± 1.2; = 0.0126), 5 years (15.5 ± 1.8; = 0.0330) and 10 years (15.4 ± 2.3; = 0.7780), compared to preoperatively (24.1 ± 2.6). Surgical success (complete and qualified) was 62.5%, 50.0%, 43.8%, 46.2%, 45.5% and 28.6% at 3 months, 6 months, 12 months, 3 years, 5 years and 10 years, respectively. There was no significant change in the number of anti-glaucoma drugs postoperatively ( > 0.05). Four eyes (25.0%) had postoperative complications (hyphaema, hypotony) that resolved after conservative management.
CONCLUSIONS
Surgical management of these complex eyes with advanced glaucoma is challenging. Overall, the cohort had good surgical outcomes with a significant decrease in IOP by 36.1% after long-term follow-up.
Topics: Aniridia; Eye Abnormalities; Follow-Up Studies; Glaucoma; Humans; Intraocular Pressure; Retrospective Studies; Trabeculectomy; Treatment Outcome; Visual Acuity
PubMed: 35001688
DOI: 10.1177/11206721211073208 -
Genes Dec 2019The transcription factor PAX6 is essential in ocular development in vertebrates, being considered the master regulator of the eye. During eye development, it is... (Review)
Review
The transcription factor PAX6 is essential in ocular development in vertebrates, being considered the master regulator of the eye. During eye development, it is essential for the correct patterning and formation of the multi-layered optic cup and it is involved in the developing lens and corneal epithelium. In adulthood, it is mostly expressed in cornea, iris, and lens. is a dosage-sensitive gene and it is highly regulated by several elements located upstream, downstream, and within the gene. There are more than 500 different mutations described to affect and its regulatory regions, the majority of which lead to haploinsufficiency, causing several ocular and systemic abnormalities. Aniridia is an autosomal dominant disorder that is marked by the complete or partial absence of the iris, foveal hypoplasia, and nystagmus, and is caused by heterozygous mutations. Other ocular abnormalities have also been associated with changes, and genotype-phenotype correlations are emerging. This review will cover recent advancements in regulation, particularly the role of several enhancers that are known to regulate during eye development and disease. We will also present an updated overview of the mutation spectrum, where an increasing number of mutations in the non-coding regions have been reported. Novel genotype-phenotype correlations will also be discussed.
Topics: Aniridia; Databases, Genetic; Eye Proteins; Gene Deletion; Genetic Association Studies; Haploinsufficiency; Humans; Mutation, Missense; PAX6 Transcription Factor; Wilms Tumor
PubMed: 31861090
DOI: 10.3390/genes10121050 -
BMC Ophthalmology May 2022Evaluate outcomes and identify prognostic factors in congenital aniridia.
BACKGROUND
Evaluate outcomes and identify prognostic factors in congenital aniridia.
METHODS
Retrospective interventional case series of patients with congenital aniridia treated between 2012-2020. Ocular examination and surgical details were collected. Surgical failure was defined as disease progression or need for additional surgery for same/related indication. Kaplan-Meier survival curves, Wilcoxon test, and univariate and multivariate linear regression analyses were performed.
RESULTS
Ninety-four patients with congenital aniridia presented at median 19.0 years. Two-thirds of patients underwent ≥ 1intraocular surgery, with average of 1.7 ± 2.3 surgeries/eye. At final follow-up (median 4.0 years), 45% of eyes had undergone lensectomy. Aphakic eyes showed worse visual acuity (VA) than phakic or pseudophakic eyes. Glaucoma affected 52% of eyes, of which half required IOP-lowering surgery. Glaucoma drainage devices showed the highest success rate (71%) at 14.2 ± 15.4 years of follow-up. Keratopathy affected 65% of eyes and one-third underwent corneal surgery. Keratoprosthesis had the longest survival rates at 10-years (64% with 95% CI [32,84]). LogMAR VA at presentation and final follow-up were not statistically different. Half of patients were legally blind at final follow-up. Final VA was associated with presenting VA, glaucoma diagnosis, and cataract or keratopathy at presentation. Penetrating keratoplasty and keratoprosthesis implantation correlated with worse BCVA.
CONCLUSIONS
Most aniridic patients in this large US-based cohort underwent at least 1 intraocular surgery. Cataract, glaucoma, and keratopathy were associated with worse VA and are important prognostic factors to consider when managing congenital aniridia.
Topics: Aniridia; Cataract; Cornea; Corneal Diseases; Follow-Up Studies; Glaucoma; Glaucoma Drainage Implants; Humans; Intraocular Pressure; Prognosis; Retrospective Studies; Treatment Outcome; Vision Disorders
PubMed: 35614435
DOI: 10.1186/s12886-022-02460-5 -
Pediatric Nephrology (Berlin, Germany) Dec 2016The oculocerebrorenal syndrome of Lowe is a rare X-linked multisystemic disorder characterized by the triad of congenital cataracts, intellectual disability, and... (Review)
Review
The oculocerebrorenal syndrome of Lowe is a rare X-linked multisystemic disorder characterized by the triad of congenital cataracts, intellectual disability, and proximal renal tubular dysfunction. Whereas the ocular manifestations and severe muscular hypotonia are the typical first diagnostic clues apparent at birth, the manifestations of incomplete renal Fanconi syndrome are often recognized only later in life. Other characteristic features are progressive severe growth retardation and behavioral problems, with tantrums. Many patients develop a debilitating arthropathy. Treatment is symptomatic, and the life span rarely exceeds 40 years. The causative oculocerebrorenal syndrome of Lowe gene (OCRL) encodes the inositol polyphosphate 5-phosphatase OCRL-1. OCRL variants have not only been found in classic Lowe syndrome, but also in patients with a predominantly renal phenotype classified as Dent disease type 2 (Dent-2). Recent data indicate that there is a phenotypic continuum between Dent-2 disease and Lowe syndrome, suggesting that there are individual differences in the ability to compensate for the loss of enzyme function. Extensive research has demonstrated that OCRL-1 is involved in multiple intracellular processes involving endocytic trafficking and actin skeleton dynamics. This explains the multi-organ manifestations of the disease. Still, the mechanisms underlying the wide phenotypic spectrum are poorly understood, and we are far from a causative therapy. In this review, we provide an update on clinical and molecular genetic findings in Lowe syndrome and the cellular and physiological functions of OCRL-1.
Topics: Adolescent; Child; Child, Preschool; Chromosome Deletion; Chromosomes, Human, Pair 11; Humans; Infant; Infant, Newborn; Molecular Biology; Mutation; Oculocerebrorenal Syndrome; WAGR Syndrome
PubMed: 27011217
DOI: 10.1007/s00467-016-3343-3 -
Annals of Translational Medicine Nov 2020Congenital cataract is a rare eye disease, one of the leading treatable causes of low vision in children worldwide. Hereditary cataracts can be divided in syndromic and... (Review)
Review
Congenital cataract is a rare eye disease, one of the leading treatable causes of low vision in children worldwide. Hereditary cataracts can be divided in syndromic and non-syndromic cataracts. Early diagnosis in congenital cataracts is key to reach good visual function. Current surgical techniques, that combine microincision cataract extraction and primary intraocular lens (IOL) implantation, have improved childhood cataract outcome. Complications include posterior capsule opacification (PCO), aphakic or pseudophakic glaucoma, uveitis, pupil displacement and IOL decentration. A recent study using a modified Delphi approach identified areas of consensus and disagreement in the management of pediatric cataract. A consensus or near consensus was achieved for 79% of the questions, however 21% of the questions remained controversial, as for IOL implantation strategy. Congenital cataracts show a highly variable phenotype and genotype, and can be related to different mutations, genetic variance, and other risk factors. Congenital cataracts can be associated with other ocular developmental abnormalities, including microphthalmia, microcornea, or aniridia and with systemic findings. Next-generation sequencing (NGS) and forthcoming new ultra-high-throughput sequencing represent excellent tools to investigate the genetic causes of congenital cataracts. A better recognition of different clinical presentations and underlying etiologies of congenital cataracts may lead to the development of new approaches to improve visual outcome after cataract surgery and promote early detection of systemic associated syndromes.
PubMed: 33313290
DOI: 10.21037/atm-20-3033 -
American Journal of Medical Genetics.... Nov 2013Approximately 1% of all live births exhibit a minor or major congenital anomaly. Of these approximately one-third display craniofacial abnormalities which are a... (Review)
Review
Approximately 1% of all live births exhibit a minor or major congenital anomaly. Of these approximately one-third display craniofacial abnormalities which are a significant cause of infant mortality and dramatically affect national health care budgets. To date, more than 700 distinct craniofacial syndromes have been described and in this review, we discuss the etiology, pathogenesis and management of facial dysostoses with a particular emphasis on Treacher Collins, Nager and Miller syndromes. As we continue to develop and improve medical and surgical care for the management of individual conditions, it is essential at the same time to better characterize their etiology and pathogenesis. Here we describe recent advances in our understanding of the development of facial dysostosis with a view towards early in utero identification and intervention which could minimize the manifestation of anomalies prior to birth. The ultimate management for any craniofacial anomaly however, would be prevention and we discuss this possibility in relation to facial dysostosis.
Topics: Abnormalities, Multiple; Chromosome Deletion; Chromosomes, Human, Pair 11; Humans; Limb Deformities, Congenital; Mandibulofacial Dysostosis; Micrognathism; WAGR Syndrome
PubMed: 24123981
DOI: 10.1002/ajmg.c.31375 -
Taiwan Journal of Ophthalmology 2018Foveal hypoplasia is a retinal disorder in which there is a lack of full development of the morphology of the fovea. The optical coherence tomography (OCT) and... (Review)
Review
Foveal hypoplasia is a retinal disorder in which there is a lack of full development of the morphology of the fovea. The optical coherence tomography (OCT) and functional findings are presented in relation to the underlying genetic and developmental conditions. Recent advancements of high-resolution OCT imaging have unveiled characteristics of foveal hypoplasia that were not detected by conventional imaging methods. An absence of a foveal pit does not necessarily imply poor visual acuity, and the maturation of the cone photoreceptors is important for the visual acuity. Regardless of the degree of the development of the inner retinal layers, the visual acuity can be preserved as in diseases such as Stickler syndrome that is a newly identified retinal disorder associated with foveal hypoplasia.
PubMed: 30637189
DOI: 10.4103/tjo.tjo_101_18