Axenfeld-Rieger Syndrome: Rare Case Presentation and Overview.
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ABSTRACT:
SUBMITTER: Agarwal P
PROVIDER: S-EPMC7410934 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposeTo present the first report of a XEN45 gel stent implantation in a female with Axenfeld-Rieger syndrome (ARS), a rare congenital anomaly caused by abnormal neural crest migration during early embryogenesis. This shows promise as new minimally invasive therapeutic option in the treatment of secondary glaucoma in ARS.ObservationsA 31-year-old female with known sporadic ARS was evaluated and treated at the Edith Wolfson Medical Center in Holon, Israel. The vision in her right eye was hand motion and 20/25 in the left eye. In the left eye the intraocular pressure (IOP) was up to 31 mmHg under maximal tolerated treatment. She refused Trabeculectomy or Glaucoma Drainage Device (GDD) surgery, but agreed to Minimally Invasive Glaucoma Surgery (MIGS). A Xen device was implanted in uneventful surgery. 15 months post operatively her IOP is 8 mmHg.ConclusionsXEN implantation, when technically feasible, is a suitable procedure in ARS. This shows promise as new minimally invasive therapeutic option in the treatment of secondary glaucoma in ARS. This has particular significance as these patients often require surgery at a young age.
| S-EPMC8933667 | biostudies-literature
Project description:BackgroundAxenfeld-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.MethodsGenetic and phenotypic characterisation of the largest reported ARS cohort through comprehensive genetic and clinical data analyses.Results128 individuals with causative variants in PITX2 or FOXC1, including 81 new cases, were investigated. Ocular anomalies showed significant overlap but with broader variability and earlier onset of glaucoma for FOXC1-related ARS. Systemic anomalies were seen in all individuals with PITX2-related ARS and the majority of those with FOXC1-related ARS. PITX2-related ARS demonstrated typical umbilical anomalies and dental microdontia/hypodontia/oligodontia, along with a novel high rate of Meckel diverticulum. FOXC1-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 FOXC1-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.ConclusionSince clinical features of ARS vary significantly based on the affected gene, it is critical that families are provided with a gene-specific diagnosis, PITX2-related ARS or FOXC1-related ARS. De Hauwere syndrome is proposed to be a FOXC1opathy.
| S-EPMC9912354 | biostudies-literature
Project description: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 FOXC1 or PITX2, 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.
| S-EPMC10013571 | biostudies-literature
Project description:BACKGROUND:The surgical management of glaucoma associated with Axenfeld-Rieger Syndrome (ARS) is poorly described in the literature. The goal of this study is to compare the effectiveness of various glaucoma surgeries on intraocular pressure (IOP) management in ARS. METHODS:Retrospective cohort study at a university hospital-based practice of patients diagnosed with ARS between 1973 and 2018. Exclusion criterion was follow-up less than 1?year. The number of eyes with glaucoma (IOP???21?mmHg with corneal edema, Haabs striae, optic nerve cupping or buphthalmos) requiring surgery was determined. The success and survival rates of goniotomy, trabeculotomy±trabeculectomy (no antifibrotics), cycloablation, trabeculectomy with anti-fibrotics, and glaucoma drainage device placement were assessed. Success was defined as IOP of 5-20?mmHg and no additional IOP-lowering surgery or visually devastating complications. Kaplan-Meier survival curves and the Wilcoxon test were used for statistical analysis. RESULTS:In 32 patients identified with ARS (median age at presentation 6.9?years, 0-58.7?years; median follow-up 5.4?years, 1.1-43.7?years), 23 (71.9%) patients were diagnosed with glaucoma at median age 6.3?years (0-57.9?years). In glaucomatous eyes (46 eyes), mean IOP at presentation was 21.8?±?9.3?mmHg (median 20?mmHg, 4-45?mmHg) on 1.0?±?1.6 glaucoma medications. Thirty-one eyes of 18 patients required glaucoma surgery with 2.2?±?1.2 IOP-lowering surgeries per eye. Goniotomy (6 eyes) showed 43% success with 4.3?±?3.9?years of IOP control. Trabeculotomy±trabeculectomy (6 eyes) had 17% success rate with 14.8?±?12.7?years of IOP control. Trabeculectomy with anti-fibrotics (14 eyes) showed 57% success with 16.5?±?13.5?years of IOP control. Ahmed© (FP7 or FP8) valve placement (8 eyes) had 25% success rate with 1.7?±?1.9?years of IOP control. Baerveldt© (250 or 350) device placement (8 eyes) showed 70% success with 1.9?±?2.3?years of IOP control. Cycloablation (4 eyes) had 33% success rate with 2.7?±?3.5?years of IOP control. At final follow-up, mean IOP (12.6?±?3.8?mmHg, median 11.8?mmHg, 7-19?mmHg) in glaucomatous eyes was significantly decreased (p?<?0.0001), but there was no difference in number of glaucoma medications (1.6?±?1.5, p?=?0.1). CONCLUSIONS:In our series, greater than 70% of patients with ARS have secondary glaucoma that often requires multiple surgeries. Trabeculectomy with anti-fibrotics and Baerveldt glaucoma drainage devices showed the greatest success in obtaining IOP control.
| S-EPMC7193416 | biostudies-literature
Project description:We encountered a case with congenital iris coloboma, omphalocele, and developmental delay with a 2.5 Mb deletion on chromosome 4q25 encompassing PITX2, leading to Axenfeld-Rieger syndrome (ARS), NEUROG2, and ANK2. ARS is characterized by the aplasia of the anterior eye, odontogenesis, and abdominal wall aplasia. In our case, iris coloboma and omphalocele were thought to be caused by PITX2 haploinsufficiency. However, these symptoms are nonspecific, and clinical symptoms alone can make it difficult to make a correct diagnosis. In addition, the genes responsible for developmental delay, among others, are not well understood. Developmental delay, in this case, might be caused due to NEUROG2 haploinsufficiency. In spite of the partial deletion of ANK2, the causative gene of long QT syndrome type 4, the electrocardiogram was normal. Genetic testing can lead to a correct diagnosis, and it may be effective in detecting complications.
| S-EPMC9935865 | biostudies-literature
Project description:Axenfeld-Rieger syndrome (ARS) is a rare autosomal dominant disorder, which encompasses a range of congential malformations affecting the anterior segment of the eye. ARS shows genetic heterogeneity and mutations of the two genes, PITX2 and FOXC1, are known to be associated with the pathogenesis. There are several excellent reviews dealing with the complexity of the phenotype and genotype of ARS. In this study, we will attempt to give a brief review of the clinical features and the relevant diagnostic approaches, together with a detailed review of published PITX2 and FOXC1 mutations.
| S-EPMC2987033 | biostudies-literature
Project description:PurposeAxenfeld-Rieger syndrome (ARS) is characterized by ocular anomalies including posterior embryotoxon, iridocorneal adhesions, corectopia/iris hypoplasia, and developmental glaucoma. Although anterior segment defects and glaucoma contribute to decreased visual acuity, the role of potential posterior segment abnormalities has not been explored. We used high-resolution retinal imaging to test the hypothesis that individuals with ARS have posterior segment pathology.MethodsThree individuals with FOXC1-ARS and 10 with PITX2-ARS completed slit-lamp and fundus photography, optical coherence tomography (OCT), OCT angiography, and adaptive optics scanning light ophthalmoscopy (AOSLO). Quantitative metrics were compared to previously published values for individuals with normal vision.ResultsAll individuals demonstrated typical anterior segment phenotypes. Average ganglion cell and inner plexiform layer thickness was lower in PITX2-ARS, consistent with the glaucoma history in this group. A novel phenotype of foveal hypoplasia was noted in 40% of individuals with PITX2-ARS (but none with FOXC1-ARS). Moreover, the depth and volume of the foveal pit were significantly lower in PITX2-ARS compared to normal controls, even excluding individuals with foveal hypoplasia. Analysis of known foveal hypoplasia genes failed to identify an alternative explanation. Foveal cone density was decreased in one individual with foveal hypoplasia and normal in six without foveal hypoplasia. Two individuals (one from each group) demonstrated non-foveal retinal irregularities with regions of photoreceptor anomalies on OCT and AOSLO.ConclusionsThese findings implicate PITX2 in the development of the posterior segment, particularly the fovea, in humans. The identified posterior segment phenotypes may contribute to visual acuity deficits in individuals with PITX2-ARS.
| S-EPMC11005067 | biostudies-literature
Project description:Mutations in the Forkhead Box C1 (FOXC1) are known to cause autosomal dominant hereditary Axenfeld-Rieger syndrome, which is a genetic disorder characterized by ocular and systemic features including glaucoma, variable dental defects, craniofacial dysmorphism and hearing loss. Due to late-onset of ocular disorders and lack of typical presentation, clinical diagnosis presents a huge challenge. In this study, we described a pathogenic in-frame variant in FOXC1 in one 5-year-old boy who is presented with hypertelorism, pupil deformation in both eyes, conductive hearing loss, and dental defects. By whole exome sequencing, we identified a 3 bp deletion in FOXC1, c.516_518delGCG (p.Arg173del) as the disease-causing variant, which was de novo and not detected in the parents, and could be classified as a "pathogenic variant" according to the American College of Medical Genetics and Genomics guidelines. After confirmation of this FOXC1 variant, clinical data on Axenfeld-Rieger syndrome-associated clinical features were collected and analyzed. Furthermore, Although the affected individual present hearing loss, however, the hearing loss is conductive and is reversible during the follow-up, which might not linke to the FOXC1 variant and is coincidental. Routine examination of FOXC1 is necessary for the genetic diagnosis of hypertelorism-associated syndrome. These findings may assist clinicians in reaching correct clinical and molecular diagnoses, and providing appropriate genetic counseling.
| S-EPMC8609746 | biostudies-literature
Project description:Haploinsufficient microdeletions within chromosome 4q25 are often associated with Axenfeld-Rieger syndrome. A de novo 4q25 deletion, 675 kb proximal to PITX2, has previously been reported once in an adult patient. The patient did not have Axenfeld-Rieger anomaly, but instead had intellectual disability and a complex behavioral phenotype with withdrawn, stereotypic, and ritualistic behavior. Array comparative genome hybridization demonstrated a smaller, overlapping 4q25 deletion in a 2-year-old patient and his mother, both having significant phenotypic overlap with the initially reported patient. All 3 patients have distinct facial features (including mild hypotelorism and subtle mandibular asymmetry), developmental delay, and complex behavioral difficulties. A genotype-phenotype correlation narrows the shared phenotype to a common COL25A1 gene aberration and proposes that the concurrent EGF gene loss has a significant impact on the phenotypic severity. Overall, our patients provide data to support the existence of a novel 4q25 proximal deletion syndrome.
| S-EPMC4988255 | biostudies-literature
Project description:BackgroundAxenfeld-Rieger syndrome (ARS) is characterized by bilateral congenital abnormalities of the anterior segment of the eye associated with abnormalities of the teeth, midface, and umbilicus. Most cases of ARS are caused by mutations in the genes encoding PITX2 or FOXC1. Here we describe a family affected by a severe form of ARS.Case presentationTwo members of this family (father and daughter) presented with typical ARS and developed severe glaucoma. The ocular phenotype was much more severe in the daughter than in the father. Magnetic resonance imaging (MRI) detected an aggressive form of meningioma in the father. There was no mutation in the PITX2 gene, determined by exon screening. We identified an intragenic deletion by quantitative genomic PCR analysis and characterized this deletion in detail.ConclusionOur findings implicate the first intragenic deletion of the PITX2 gene in the pathogenesis of a severe form of ARS in an affected family. This study stresses the importance of a systematic search for intragenic deletions in families affected by ARS and in sporadic cases for which no mutations in the exons or introns of PITX2 have been found. The molecular genetics of some ARS pedigrees should be re-examined with enzymes that can amplify medium and large genomic fragments.
| S-EPMC1684248 | biostudies-literature