Spectrum of congenital and inherited ocular disorders seen in a genetic clinic: Experience of a developing ocular genetic service

Purpose: Hereditary causes are an important etiological category of childhood blindness. This study reports the real?world experience of a developing ocular genetic service. Methods: The study was carried out from Jan 2020 to Dec 2021 jointly by the Pediatric Genetic Clinic and the Department of Ophthalmology of a tertiary care hospital in North?West India. Children presenting to the genetic clinic with congenital or late?onset ocular disorder(s) and any individual (irrespective of age) suffering from an ophthalmic disorder and referred by an ophthalmologist for genetic counseling for himself/herself and/or his/her family member(s) were included. Genetic testing (exome sequencing/panel?based sequencing/chromosomal microarray) was outsourced to third?party laboratories with the cost of the test being borne by the patient. Results: Exactly 8.6% of the registered patients in the genetic clinic had ocular disorders. Maximum number of patients belonged to the category of anterior segment dysgenesis, followed by microphthalmia anophthalmia coloboma spectrum, lens disorders, and inherited retinal disorders in decreasing numbers. The ratio of syndromic ocular to isolated ocular disorders seen was 1.8:1. Genetic testing was accepted by 55.5% of families. The genetic testing was clinically useful for ~35% of the tested cohort, with the opportunity for prenatal diagnosis being the most useful application of genetic testing. Conclusion: Syndromic ocular disorders are seen at a higher frequency compared to isolated ocular disorders in a genetic clinic. Opportunity for prenatal diagnosis is the most useful application of genetic testing in ocular disorders.

Axenfeld-Rieger Syndrome: Case Report

Aims:To describe a Axenfeld-Rieger Syndrome.Presentation of Case: MCL, 7 years old, female, brown, was taken to the ophthalmology outpatient clinic of the Hospital Universit醨io Ant鬾io Pedro, Brazil by her parents, complaining of low visual acuity and malformation of the pupil perceived since birth.Discussion: Axenfeld-Rieger Syndrome is a rare and hereditary disease. Clinically, Axenfeld's anomaly is characterized by the presence of posterior embryotoxon, and there may be adherence of iridian tissue in its periphery. In addition to Rieger's anomaly, posterior embryotoxon is added to iris hypoplasia and iris thickness defects, uveal ectropion and pupillary alterations, such as corectopia. Rieger's syndrome is associated with extraocular changes, of which hypodontia, myicrodontia, maxillary hypoplasia, telecanthus, hypertelorism and hypospadias stand out.Conclusions: Therefore, the importance of early diagnosis, follow-up and adequate treatment becomes evident in order to preserve the visual function of patients and thus avoid an unfavorable evolution.

Anterior segment dysgenesis and secondary glaucoma in Goldenhar syndrome

A 3-year-old girl presented with a history of watering, haze and increase in the size of the right eye for two months. The child had bilateral preauricular skin tags, limbal dermoid and dermolipoma, consistant with the diagnosis of Goldenhad syndrome. In addition, her right eye manifested enlarged cornea, flat anterior chamber, atrophic iris and elevated intraocular pressure. This case report highlights a possible association of anterior segment dysgenesis and glaucoma with Goldenhar syndrome.

Disease genes detection of two anterior segment dysgenesis pedigree by whole exome sequence / 眼科新进展

Objective To identify the disease-causing gene mutation in families with anterior segment dysgenesis (ASD).Methods Two ASD families coming from Henan and Hebei provinces were enrolled in this study.Ocular examinations were performed,and periphery blood specimens were collected from each family member under the informed consent.The blood samples of 2 patients and 1 normal person in family 1 and 1 patient and 1 normal person in family 2 were analyzed by the whole exome sequences.The candidate genes were verified by Sanger sequence and predicted damages by PolyPhen-2 and SIFT Human Splicing Finder software.Results Family 1 including 9 patients were examined in serial 3 passages,which conformed to autosomal dominant inheritance pattern.Clinical examination revealed binocular anterior segment dysgenesis in the 9 patients.There were 13 SNV and 55 InDel candidate mutations.And missense mutation c.T2A(p.M1K)on PAX6 gene was found.Family 2 included 8 members,and 2 patients were examined.The splicing mutation c.357 + 1g ＞ c on the same gene was found.Conclusion T2A(p.M1 K) and c.357 + 1 g ＞ c mutations in PAX6 gene are responsible for ASD.Whole exome sequence provides a new approach to detect diseasecausing mutation of ASD with diversity clinical phenotypes.

A Family with Axenfeld-Rieger Syndrome: Report of the Clinical and Genetic Findings

PURPOSE: To describe clinical findings in a Korean family with Axenfeld-Rieger syndrome. METHODS: A retrospective review of clinical data about patients with diagnosed Axenfeld-Rieger syndrome. Five affected members of the family underwent a complete ophthalmologic examination. We screened the forkhead box C1 gene and the pituitary homeobox 2 gene in patients. Peripheral blood leukocytes and buccal mucosal epithelial cells were obtained from seven members of a family with Axenfeld-Rieger syndrome. DNA was extracted and amplified by polymerase chain reaction, followed by direct sequencing. RESULTS: The affected members showed iris hypoplasia, iridocorneal adhesions, posterior embryotoxon, and advanced glaucoma in three generation. None had systemic anomalies. Two mutations including c.1362_1364insCGG and c.1142_1144insGGC were identified in forkhead box C1 in four affected family members. CONCLUSIONS: This study may help to understand clinical findings and prognosis for patients with Axenfeld-Rieger syndrome.

Novel occurrence of Axenfeld: Rieger syndrome in a patient with blepharophimosis ptosis epicanthus inversus syndrome.

is a complex eyelid malformation characterized by the classical tetrad of blepharophimosis, telecanthus, ptosis, and epicanthus inversus. It has been reported to be associated with other ocular anomalies such as euryblepharon, strabismus, nystagmus, amblyopia, microphthalmos, lacrimal drainage apparatus abnormality, extra ocular muscle abnormalities, microcornea, trabecular dysgenesis, optic nerve hypoplasias, and colobomas of the optic disk. We describe a case of BPES with Axenfeld–Rieger syndrome, a neurocristopathy characterized by maldevelopment of the anterior segment with predisposition to development of glaucoma. Interestingly, both syndromes are caused by mutations in the same class of genes, namely the winged‑helix/ forked transcription factors (FOX) involved in a variety of developmental processes.

Glaucoma en anomalía de Rieger / Glaucoma in Rieger's anomaly

Se describe un caso clínico con diagnóstico de anomalía de Rieger con embriotoxon posterior, adherencias iridocorneales, corectopia, atrofia sectorial del iris, goniodisgenesia y glaucoma bilateral no asociado a alteraciones sistémicas. Se decide realizar trabeculo-trabeculectomía con Mitomicina C. en ambos ojos manteniéndose compensado hasta el año de la cirugía con posterior adelgazamiento de la bula de filtración y salida de humor acuoso de ojo izquierdo con notable disminución de la presión intraocular, decidiéndose realizar reconstrucción de bula de filtración. Al mes de la cirugía las presiones intraoculares comenzaron a elevarse, encontrándose en estos momentos compensadas con dorzolamida colirio

A clinical case, who was diagnosed with Rieger's anomaly with later embriotoxon, iridocorneal adhesions, corectopia, sectoral atrophy of the iris, goniodysgenesis and bilateral glaucoma unrelated to systemic alterations, was described. The performance of trabeculo-trabeculectomy with Mitomycin C was decided for both eyes. The case remained compensated till one year after surgery, when there occurs thinning of the filtration bulla and aqueous humor discharge from the left eye in addition to remarkable decrease of intraocular pressure. It was then decided to reconstruct the filtering bulla. One month after surgery, the intraocular pressure began rising and they are presently compensated with the use of dorzolamide drops