-
Clinical Genetics Jun 2018Axenfeld-Rieger syndrome (ARS) is a clinically and genetically heterogeneous group of developmental disorders affecting primarily the anterior segment of the eye, often... (Review)
Review
Axenfeld-Rieger syndrome (ARS) is a clinically and genetically heterogeneous group of developmental disorders affecting primarily the anterior segment of the eye, often leading to secondary glaucoma. Patients with ARS may also present with systemic changes, including dental defects, mild craniofacial dysmorphism, and umbilical anomalies. ARS is inherited in an autosomal-dominant fashion; the underlying defect in 40% of patients is mutations in PITX2 or FOXC1. Here, an overview of the clinical spectrum of ARS is provided. As well, the known underlying genetic defects, clinical diagnostic possibilities, genetic counseling and treatments of ARS are discussed in detail.
Topics: Anterior Eye Segment; Eye Abnormalities; Eye Diseases, Hereditary; Genetic Association Studies; Genetic Counseling; Genetic Predisposition to Disease; Humans
PubMed: 28972279
DOI: 10.1111/cge.13148 -
Journal of Medical Genetics Apr 2023Axenfeld-Rieger syndrome (ARS) is characterised by typical anterior segment anomalies, with or without systemic features. The discovery of causative genes identified ARS...
BACKGROUND
Axenfeld-Rieger syndrome (ARS) is characterised by typical anterior segment anomalies, with or without systemic features. The discovery of causative genes identified ARS subtypes with distinct phenotypes, but our understanding is incomplete, complicated by the rarity of the condition.
METHODS
Genetic and phenotypic characterisation of the largest reported ARS cohort through comprehensive genetic and clinical data analyses.
RESULTS
128 individuals with causative variants in or , including 81 new cases, were investigated. Ocular anomalies showed significant overlap but with broader variability and earlier onset of glaucoma for -related ARS. Systemic anomalies were seen in all individuals with -related ARS and the majority of those with -related ARS. -related ARS demonstrated typical umbilical anomalies and dental microdontia/hypodontia/oligodontia, along with a novel high rate of Meckel diverticulum. -related ARS exhibited characteristic hearing loss and congenital heart defects as well as previously unrecognised phenotypes of dental enamel hypoplasia and/or crowding, a range of skeletal and joint anomalies, hypotonia/early delay and feeding disorders with structural oesophageal anomalies in some. Brain imaging revealed highly penetrant white matter hyperintensities, colpocephaly/ventriculomegaly and frequent arachnoid cysts. The expanded phenotype of -related ARS identified here was found to fully overlap features of De Hauwere syndrome. The results were used to generate gene-specific management plans for the two types of ARS.
CONCLUSION
Since clinical features of ARS vary significantly based on the affected gene, it is critical that families are provided with a gene-specific diagnosis, -related ARS or -related ARS. De Hauwere syndrome is proposed to be a FOXC1opathy.
Topics: Humans; Homeodomain Proteins; Transcription Factors; Anterior Eye Segment; Eye Abnormalities; Forkhead Transcription Factors; Mutation
PubMed: 35882526
DOI: 10.1136/jmg-2022-108646 -
Taiwan Journal of Ophthalmology 2023Axenfeld-Rieger syndrome (ARS) is a rare autosomal-dominant neurocristopathy that presents with a variety of classical ocular and systemic findings. The pathophysiology... (Review)
Review
Axenfeld-Rieger syndrome (ARS) is a rare autosomal-dominant neurocristopathy that presents with a variety of classical ocular and systemic findings. The pathophysiology of the disease involves anterior segment dysgenesis, and patients may present with ophthalmic complications early in life, including secondary glaucoma, high refractive errors, amblyopia, and permanent visual damage. There are a limited number of studies in the literature that focus primarily on pediatric patients with ARS. The purpose of this article was to review the current literature on clinical presentation, genetic associations, diagnosis, secondary complications, and treatment of ARS in pediatric patients. Evaluating the essential clinical aspects of the disease in children may allow for earlier diagnosis and treatment and prevent visual morbidity from amblyopia and secondary glaucoma that may result in permanent visual damage.
PubMed: 38249500
DOI: 10.4103/tjo.TJO-D-23-00089 -
BMC Ophthalmology Dec 2022Axenfeld-Rieger syndrome (ARS) is a rare kind of anterior segment dysgenesis (ASD). The most common ocular features of ARS are posterior embryotoxon and iris hypoplasia,... (Review)
Review
BACKGROUND
Axenfeld-Rieger syndrome (ARS) is a rare kind of anterior segment dysgenesis (ASD). The most common ocular features of ARS are posterior embryotoxon and iris hypoplasia, while some patients may manifest as corneal opacity and edema. However, the current understanding of how ARS affects the cornea is still incomplete. This study reports a novel histopathological finding of ARS, complicating corneal abnormalities, including congenital corneal opacity and irreversible endothelial decompensation.
METHODS
This retrospective study included 6 eyes of 3 ARS patients, 5 of which underwent keratoplasty for irreversible endothelial decompensation from May 2016 to January 2019. No eye had a history of surgery. We reviewed the data of epidemiology, clinical manifestations and histopathologic examinations.
RESULTS
Five eyes developed irreversible endothelial decompensation, among which 4 were born with corneal opacity. One eye exhibited transparent cornea but showed a continuous loss of endothelial cells in the absence of surgery and elevated intraocular pressure thereafter. Anterior segment optical coherence tomography photographs showed that anterior synechia existed in the area with corneal opacities, where we found the interlayer splitting of the Descemet membrane inserted by hypoplastic iris and a basement membrane-like structure under a light microscope.
CONCLUSION
Anterior synechia might be associated with corneal abnormalities in ARS patients. The novel histopathologic finding revealed the internal relation between anterior segment dysgenesis and would help explore the inner mechanism of corneal abnormalities in ARS.
Topics: Humans; Endothelial Cells; Retrospective Studies; Anterior Eye Segment; Eye Abnormalities; Corneal Diseases; Corneal Opacity; Iris Diseases
PubMed: 36577962
DOI: 10.1186/s12886-022-02754-8 -
Heliyon Jul 2023Axenfeld-Rieger Syndrome (ARS) is comprised of a group of autosomal dominant disorders that are each characterized by anterior segment abnormalities of the eye.... (Review)
Review
Axenfeld-Rieger Syndrome (ARS) is comprised of a group of autosomal dominant disorders that are each characterized by anterior segment abnormalities of the eye. Mutations in the transcription factors or are the most well-studied genetic manifestations of this syndrome. Due to the rarity this syndrome, ARS-associated neurological manifestations have not been well characterized. The purpose of this systematic review is to characterize and describe ARS neurologic manifestations that affect the cerebral vasculature and their early and late sequelae. PRISMA guidelines were followed; studies meeting inclusion criteria were analyzed for study design, evidence level, number of patients, patient age, whether the patients were related, genotype, ocular findings, and nervous system findings, specifically neurostructural and neurovascular manifestations. 63 studies met inclusion criteria, 60 (95%) were case studies or case series. The gene was most commonly found, followed by , then . The most commonly described structural neurological findings were white matter abnormalities in 26 (41.3%) of studies, followed by Dandy-Walker Complex 12 (19%), and agenesis of the corpus callosum 11 (17%). Neurovascular findings were examined in 6 (9%) of studies, identifying stroke, cerebral small vessel disease (CSVD), tortuosity/dolichoectasia of arteries, among others, with no mention of moyamoya. This is the first systematic review investigating the genetic, neurological, and neurovascular associations with ARS. Structural neurological manifestations were common, yet often benign, perhaps limiting the utility of MRI screening. Neurovascular abnormalities, specifically stroke and CSVD, were identified in this population. Stroke risk was present in the presence and absence of cardiac comorbidities. These findings suggest a relationship between ARS and neurovascular findings; however, larger scale studies are necessary inform therapeutic decisions.
PubMed: 37539177
DOI: 10.1016/j.heliyon.2023.e18225 -
Clinical Ophthalmology (Auckland, N.Z.) 2023Axenfeld-Rieger syndrome (ARS) is a rare congenital disease that is primarily characterized by ocular anterior segment anomalies but is also associated with... (Review)
Review
Axenfeld-Rieger syndrome (ARS) is a rare congenital disease that is primarily characterized by ocular anterior segment anomalies but is also associated with craniofacial, dental, cardiac, and neurologic abnormalities. Over half of cases are linked with autosomal dominant mutations in either or , which reflects the molecular role of these genes in regulating neural crest cell contributions to the eye, face, and heart. Within the eye, ARS is classically defined as the combination of posterior embryotoxon with iris bridging strands (Axenfeld anomaly) and iris hypoplasia causing corectopia and pseudopolycoria (Rieger anomaly). Glaucoma due to iridogoniodysgenesis is the main source of morbidity and is typically diagnosed during infancy or childhood in over half of affected individuals. Angle bypass surgery, such as glaucoma drainage devices and trabeculectomies, is often needed to obtain intraocular pressure control. A multi-disciplinary approach including glaucoma specialists and pediatric ophthalmologists produces optimal outcomes as vision is dependent on many factors including glaucoma, refractive error, amblyopia and strabismus. Further, since ophthalmologists often make the diagnosis, it is important to refer patients with ARS to other specialists including dentistry, cardiology, and neurology.
PubMed: 36926528
DOI: 10.2147/OPTH.S379853 -
The British Journal of Ophthalmology Mar 2012Axenfeld-Rieger syndrome is a genetic disease affecting multiple organ systems. In the eye, this condition manifests with varying degrees of anterior segment dysgenesis... (Review)
Review
Axenfeld-Rieger syndrome is a genetic disease affecting multiple organ systems. In the eye, this condition manifests with varying degrees of anterior segment dysgenesis and carries a high risk of glaucoma. Other associated systemic issues include cardiovascular outflow tract malformations, craniofacial abnormalities and pituitary abnormalities, which can result in severe endocrinological sequelae. Recent advances in molecular genetics have identified two major genes, PITX2 and FOXC1, demonstrating a wide spectrum of mutations, which aids in the molecular diagnosis of the disease, although evidence exists to implicate other loci in this condition. The management of individuals affected by Axenfeld-Rieger syndrome requires a multidisciplinary approach and would include dedicated surveillance and management of glaucoma, sensorineural hearing loss, and cardiac, endocrinological, craniofacial and orthopaedic abnormalities.
Topics: Anterior Eye Segment; Eye Abnormalities; Eye Diseases, Hereditary; Forkhead Transcription Factors; Homeodomain Proteins; Humans; Transcription Factors; Homeobox Protein PITX2
PubMed: 22199394
DOI: 10.1136/bjophthalmol-2011-300801 -
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 -
Journal Francais D'ophtalmologie May 2018
Topics: Abnormalities, Multiple; Anterior Eye Segment; Cataract; Child; Ectropion; Eye Abnormalities; Eye Diseases, Hereditary; Female; Glaucoma; Humans; Iris; Morocco; Trabeculectomy
PubMed: 29793789
DOI: 10.1016/j.jfo.2017.10.010