Macular hypoplasia in congenital disorder of glycosylation type 1a

Congenital disorders of glycosylation are a rare group of metabolic disorders that can result in multiorgan disease. This article describes a novel finding of macular hypoplasia in congenital disorders of glycosylation type 1a

Mutations in the EPHA2 gene are a major contributor to inherited cataracts in South-Eastern Australia.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Congenital cataract is the most common cause of treatable visual impairment in children worldwide. Mutations in many different genes lead to congenital cataract. Recently, mutations in the receptor tyrosine kinase gene, EPHA2, have been found to cause congenital cataract in six different families. Although these findings have established EPHA2 as a causative gene, the total contribution of mutations in this gene to congenital cataract is unknown. In this study, for the first time, a population-based approach was used to investigate the frequency of disease causing mutations in the EPHA2 gene in inherited cataract cases in South-Eastern Australia. A cohort of 84 familial congenital or juvenile cataract index cases was screened for mutations in the EPHA2 gene by direct sequencing. Novel changes were assessed for segregation with the disease within the family and in unrelated controls. Microsatellite marker analysis was performed to establish any relationship between families carrying the same mutation. We report a novel congenital cataract causing mutation c.1751C.T in the EPHA2 gene and the previously reported splice mutation c.2826-9G.A in two new families. Additionally, we report a rare variant rs139787163 potentially associated with increased susceptibility to cataract. Thus mutations in EPHA2 account for 4.7% of inherited cataract cases in South-Eastern Australia. Interestingly, the identified rare variant provides a link between congenital and age-related cataract

Orbital Subperiosteal Hematoma in the Newborn Causing Unilateral Proptosis: Ultrasound as First-Line Imaging Modality

This journal is published under the Creative Commons license CC BY-NC-ND (Attribution-NonCommercial-NoDerivatives)Proptosis in the neonatal period is relatively infrequent and has diverse underlying etiologies. One of the more common causes appears to be orbital subperiosteal hematoma. Early detection, differentiation from other causes, and regular follow-up are essential as loss of vision can occur. We describe two cases of neonatal proptosis caused by orbital subperiosteal hematoma highlighting different diagnostic and management approaches, and provide a summary of previously reported cases. Spontaneous resolution occurs in most cases; however, emergent surgical evacuation is warranted in cases of optic nerve compression. This is the first report to provide orbital ultrasound images of uncomplicated neonatal orbital subperiosteal hematoma. Orbital ultrasound followed by magnetic resonance imaging (MRI) is a valid nonradiation approach for assessing neonatal proptosis due to subperiosteal orbital hematoma

Biallelic CPAMD8 variants are a frequent cause of childhood and juvenile open-angle glaucoma

Purpose: Developmental abnormalities of the ocular anterior segment in some cases can lead to ocular hypertension and glaucoma. CPAMD8 is a gene of unknown function recently associated with ocular anterior segment dysgenesis, myopia, and ectopia lentis. We sought to assess the contribution of biallelic CPAMD8 variants to childhood and juvenile open-angle glaucoma. Design: Retrospective, multicenter case series. Participants: A total of 268 probands and their relatives with a diagnosis of childhood or juvenile open-angle glaucoma. Methods: Patients underwent a comprehensive ophthalmic assessment, with DNA from patients and their relatives subjected to genome, exome, or capillary sequencing. CPAMD8 RNA expression analysis was performed on tissues dissected from cadaveric human eyes. Main outcome measures: Diagnostic yield within a cohort of childhood and juvenile open-angle glaucoma, prevalence and risk of ophthalmic phenotypes, and relative expression of CPAMD8 in the human eye. Results: We identified rare (allele frequency -5) biallelic CPAMD8 variants in 5.7% (5/88) of probands with childhood glaucoma and 2.1% (2/96) of probands with juvenile open-angle glaucoma. When including family members, we identified 11 individuals with biallelic variants in CPAMD8 from 7 unrelated families. Nine of these individuals were diagnosed with glaucoma (9/11, 81.8%), with a mean age at diagnosis of 9.22±14.89 years, and all individuals with glaucoma required 1 or more incisional procedures to control high intraocular pressure. Iris abnormalities were observed in 9 of 11 individuals, cataract was observed in 8 of 11 individuals (72.7%), and retinal detachment was observed in 3 of 11 individuals (27.3%). CPAMD8 expression was highest in neural crest-derived tissues of the adult anterior segment, suggesting that CPAMD8 variation may cause malformation or obstruction of key drainage structures. Conclusions: Biallelic CPAMD8 variation was associated with a highly heterogeneous phenotype and in our cohorts was the second most common inherited cause of childhood glaucoma after CYP1B1 and juvenile open-angle glaucoma after MYOC. CPAMD8 sequencing should be considered in the investigation of both childhood and juvenile open-angle glaucoma, particularly when associated with iris abnormalities, cataract, or retinal detachment

Biallelic CPAMD8 Variants Are a Frequent Cause of Childhood and Juvenile Open-Angle Glaucoma

© 2020 by the American Academy of Ophthalmology. This is an open access article under the CC BY-NC-ND licensePurpose Developmental abnormalities of the ocular anterior segment in some cases can lead to ocular hypertension and glaucoma. CPAMD8 is a gene of unknown function recently associated with ocular anterior segment dysgenesis, myopia, and ectopia lentis. We sought to assess the contribution of biallelic CPAMD8 variants to childhood and juvenile open-angle glaucoma. Design Retrospective, multicenter case series. Participants A total of 268 probands and their relatives with a diagnosis of childhood or juvenile open-angle glaucoma. Purpose Developmental abnormalities of the ocular anterior segment in some cases can lead to ocular hypertension and glaucoma. CPAMD8 is a gene of unknown function recently associated with ocular anterior segment dysgenesis, myopia, and ectopia lentis. We sought to assess the contribution of biallelic CPAMD8 variants to childhood and juvenile open-angle glaucoma. Methods Patients underwent a comprehensive ophthalmic assessment, with DNA from patients and their relatives subjected to genome, exome, or capillary sequencing. CPAMD8 RNA expression analysis was performed on tissues dissected from cadaveric human eyes. Main Outcome Measures Diagnostic yield within a cohort of childhood and juvenile open-angle glaucoma, prevalence and risk of ophthalmic phenotypes, and relative expression of CPAMD8 in the human eye. Results We identified rare (allele frequency < 4×10−5) biallelic CPAMD8 variants in 5.7% (5/88) of probands with childhood glaucoma and 2.1% (2/96) of probands with juvenile open-angle glaucoma. When including family members, we identified 11 individuals with biallelic variants in CPAMD8 from 7 unrelated families. Nine of these individuals were diagnosed with glaucoma (9/11, 81.8%), with a mean age at diagnosis of 9.22±14.89 years, and all individuals with glaucoma required 1 or more incisional procedures to control high intraocular pressure. Iris abnormalities were observed in 9 of 11 individuals, cataract was observed in 8 of 11 individuals (72.7%), and retinal detachment was observed in 3 of 11 individuals (27.3%). CPAMD8 expression was highest in neural crest–derived tissues of the adult anterior segment, suggesting that CPAMD8 variation may cause malformation or obstruction of key drainage structures. Conclusions Biallelic CPAMD8 variation was associated with a highly heterogeneous phenotype and in our cohorts was the second most common inherited cause of childhood glaucoma after CYP1B1 and juvenile open-angle glaucoma after MYOC. CPAMD8 sequencing should be considered in the investigation of both childhood and juvenile open-angle glaucoma, particularly when associated with iris abnormalities, cataract, or retinal detachment

Dandy-Walker Phenotype with Brainstem Involvement: 2 Distinct Subgroups with Different Prognosis.

BACKGROUND AND PURPOSE: Although cardinal imaging features for the diagnostic criteria of the Dandy-Walker phenotype have been recently defined, there is a large range of unreported malformations among these patients. The brainstem, in particular, deserves careful attention because malformations in this region have potentially important implications for clinical outcomes. In this article, we offer detailed information on the association of brainstem dysgenesis in a large, multicentric cohort of patients with the Dandy-Walker phenotype, defining different subtypes of involvement and their potential clinical impact. MATERIALS AND METHODS: In this established multicenter cohort of 329 patients with the Dandy-Walker phenotype, we include and retrospectively review the MR imaging studies and clinical records of 73 subjects with additional brainstem malformations. Detailed evaluation of the different patterns of brainstem involvement and their potential clinical implications, along with comparisons between posterior fossa measurements for the diagnosis of the Dandy-Walker phenotype, was performed among the different subgroups of patients with brainstem involvement. RESULTS: There were 2 major forms of brainstem involvement in patients with Dandy-Walker phenotype including the following: 1) the mild form with anteroposterior disproportions of the brainstem structures only (57/73; 78%), most frequently with pontine hypoplasia (44/57; 77%), and 2) the severe form with patients with tegmental dysplasia with folding, bumps, and/or clefts (16/73; 22%). Patients with severe forms of brainstem malformation had significantly increased rates of massive ventriculomegaly, additional malformations involving the corpus callosum and gray matter, and interhemispheric cysts. Clinically, patients with the severe form had significantly increased rates of bulbar dysfunction, seizures, and mortality. CONCLUSIONS: Additional brainstem malformations in patients with the Dandy-Walker phenotype can be divided into 2 major subgroups: mild and severe. The severe form, though less prevalent, has characteristic imaging features, including tegmental folding, bumps, and clefts, and is directly associated with a more severe clinical presentation and increased mortality

The Grizzly, October 22, 1991

Alumni Return for Homecoming Celebration • Phi Beta Kappa Charter Approved for Ursinus • Thomas Confirmed to Supreme Court • Gibson to Speak at Ursinus • GALA Seeks Recognition • U.S.G.A. Minutes • GALA Comes Out • Modern Medical Imaging • The Vision of Science Through Art • Beware of Bad Moods • Woman Fixing Her Hair? • Critics\u27 Corner: The Fisher King; Sleeping With the Enemy • Giggles Night Club Comedians • Letters: In Defense of Harley; Harassment Response; An Appeal for the Trees • Apples and Oranges • Dining Turf • Bears Blank the Bullets in Homecoming Game • Cross Country Runs to Victory • Field Hockey Strikes Back, Raises Record to 5-5-2 • Volleyball Spikes Cabrini • Lady Bears Cruise to 1st Place • Winds Fill Ursinus\u27 Sails • Soccer Bounces Back with Three Straight Winshttps://digitalcommons.ursinus.edu/grizzlynews/1280/thumbnail.jp

Current state of perinatal postmortem magnetic resonance imaging: European Society of Paediatric Radiology questionnaire-based survey and recommendations.

BACKGROUND: Postmortem magnetic resonance imaging (MRI) in perinatal and childhood deaths is increasingly used as a noninvasive adjunct or alternative to autopsy. Imaging protocols vary between centres and consensus guidelines do not exist. OBJECTIVE: Our aim was to develop practical, standardised recommendations for perinatal postmortem MRI. MATERIALS AND METHODS: Recommendations were based on the results of two surveys regarding local postmortem MRI practices sent electronically to all 14 members of the European Society of Paediatric Radiology (ESPR) Postmortem Imaging Task Force and 17 members of the International Society of Forensic Radiology and Imaging Task Force (25 different centres). RESULTS: Overall, 11/14 (78.6%) respondents from different institutions perform postmortem MRI. All of these centres perform postmortem MRI for perinatal and neonatal deaths, but only 6/11 (54.5%) perform imaging in older children. CONCLUSION: We propose a clinical standard for postmortem MRI sequences plus optional sequences for neuroimaging and cardiac anatomy depending on available scanning time and referral indications

Partial duplication of the CRYBB1-CRYBA4 locus is associated with autosomal dominant congenital cataract

This author accepted manuscript is made available following 6 month embargo from date of publication (March 2017) in accordance with the publisher’s copyright policyCongenital cataract is a rare but severe paediatric visual impediment, often caused by variants in one of several crystallin genes that produce the bulk of structural proteins in the lens. Here we describe a pedigree with autosomal dominant isolated congenital cataract and linkage to the crystallin gene cluster on chromosome 22. No rare single nucleotide variants or short indels were identified by exome sequencing, yet copy number variant analysis revealed a duplication spanning both CRYBB1 and CRYBA4. While the CRYBA4 duplication was complete, the CRYBB1 duplication was not, with the duplicated CRYBB1 product predicted to create a gain of function allele. This association suggests a new genetic mechanism for the development of isolated congenital cataract