Long-Term Visual Outcomes in Prematurely Born Children.

Purpose: Prematurely born children are at risk of numerous complications that affect the visual system. Retinopathy of prematurity (ROP) and cerebral visual impairment (CVI) are among two major causes of childhood blindness and visual impairment in industrialized nations, and large countries with emerging economies are seeing increasing childhood blindness from ROP alone, adding to the burden of disease worldwide. The purpose of this paper is to review the long-term impacts of prematurity, ROP and CVI on vision in children who were born preterm.

Recurrence of a BBS1 variant in Bardet-Biedl patients from Prince Edward Island.

This study reports variants in BBS1 and BBS7 in patients with Bardet-Biedl syndrome from the Canadian Maritime provinces. The BBS1 variant NM_024649.5:c.

Severe Familial Exudative Vitreoretinopathy, Congenital Hearing Loss, and Developmental Delay in a Child With Biallelic Variants in FZD4.

Importance: Familial exudative vitreoretinopathy (FEVR) is a nonsyndromic autosomal dominant retinal disorder commonly caused by variants in the FZD4 gene. This study investigates the potential role beyond ocular abnormalities for FZD4 gene variants in patients with FEVR.

Objective: To evaluate the role of FZD4 in symptoms beyond those associated with FEVR through a patient with biallelic variants in FZD4.

Psychosocial Distress in Parents with Children Awaiting Surgery during the COVID-19 Pandemic.

Due to resource restrictions related to the COVID-19 pandemic, many pediatric patients are facing substantial delays for surgery, potentially resulting in additional distress for caregivers. We aimed to assess the experiences and psychosocial distress of parents during COVID-19 as they relate to the pandemic, waiting for surgery, and the combined effects of both events. The was a cross-sectional qualitative study.

Binocularity outcomes following treatment for retinopathy of prematurity.

Objective: Retinopathy of prematurity (ROP) is a leading cause of childhood visual impairment. Treatment options for severe ROP include laser and/or anti-vascular endothelial growth factor (anti-VEGF) injections. Previous studies have compared the 2 treatments for functional outcomes including visual acuity, amblyopia, and strabismus.

Frizzled 4 regulates ventral blood vessel remodeling in the zebrafish retina.

Background: Familial exudative vitreoretinopathy (FEVR) is a rare congenital disorder characterized by a lack of blood vessel growth to the periphery of the retina with secondary fibrovascular proliferation at the vascular-avascular junction. These structurally abnormal vessels cause leakage and hemorrhage, while the fibroproliferative scarring results in retinal dragging, detachment and blindness. Mutations in the FZD4 gene represent one of the most common causes of FEVR.

Optimized knock-in of point mutations in zebrafish using CRISPR/Cas9.

We have optimized point mutation knock-ins into zebrafish genomic sites using clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 reagents and single-stranded oligodeoxynucleotides. The efficiency of knock-ins was assessed by a novel application of allele-specific polymerase chain reaction and confirmed by high-throughput sequencing. Anti-sense asymmetric oligo design was found to be the most successful optimization strategy.

Fzd4 Haploinsufficiency Delays Retinal Revascularization in the Mouse Model of Oxygen Induced Retinopathy.

Mutations in genes that code for components of the Norrin-FZD4 ligand-receptor complex cause the inherited childhood blinding disorder familial exudative vitreoretinopathy (FEVR). Statistical evidence from studies of patients at risk for the acquired disease retinopathy of prematurity (ROP) suggest that rare polymorphisms in these same genes increase the risk of developing severe ROP, implying that decreased Norrin-FZD4 activity predisposes patients to more severe ROP. To test this hypothesis, we measured the development and recovery of retinopathy in wild type and Fzd4 heterozygous mice in the absence or presence of ocular ischemic retinopathy (OIR) treatment.

Stability of Attitudes to the Ethical Issues Raised by the Return of Incidental Genomic Research Findings in Children: A Follow-Up Study.

Objective: We explore the stability of parental attitudes to the ethical issues raised by the return of genomic research results.

Methods: A 19-item questionnaire was mailed to participants in a large genome research consortium 18 months following a baseline survey. We describe the stability of parental attitudes to (a) sharing of genomic research results, (b) endorsement of children in genomic research, (c) responsibilities of researchers, and (d) responsibilities to extended family.

Congenital Bilateral Retinal Detachment in Two Siblings with Osteoporosis-Pseudoglioma Syndrome.

The birth of a bilaterally blind child is catastrophic for families and a challenging diagnostic and management problem for ophthalmologists. Early identification of the underlying cause and its genetic basis helps initiate possible treatment, delineate prognosis, and identify risks for future pregnancies. In some cases, an early diagnosis can also influence the treatment of other family members.

Phenotypic overlap between familial exudative vitreoretinopathy and microcephaly, lymphedema, and chorioretinal dysplasia caused by KIF11 mutations.

Importance: Retinal detachment with avascularity of the peripheral retina, typically associated with familial exudative vitreoretinopathy (FEVR), can result from mutations in KIF11, a gene recently identified to cause microcephaly, lymphedema, and chorioretinal dysplasia (MLCRD) as well as chorioretinal dysplasia, microcephaly, and mental retardation (CDMMR). Ophthalmologists should be aware of the range of presentations for mutations in KIF11 because the phenotypic distinction between FEVR and MLCRD/CDMMR portends management implications in patients with these conditions.

Objective: To identify gene mutations in patients who present with a FEVR phenotype and explore the spectrum of ocular and systemic abnormalities caused by KIF11 mutations in a cohort of patients with FEVR or microcephaly in conjunction with chorioretinopathy or FEVR.

Has rising pediatric obesity increased the incidence of idiopathic intracranial hypertension in children?

Objective: Idiopathic intracranial hypertension (IIH) in children is an uncommon but significant cause of morbidity, including permanent visual loss. It is important to understand if, like obesity, IIH in children is on the rise and is related to that increase. The aim of this study is to compare the recent incidence rate of pediatric IIH in a tertiary care hospital with earlier data published from that same hospital.

Attitudes of parents toward the return of targeted and incidental genomic research findings in children.

Purpose: We describe parental attitudes toward the return of targeted and incidental genomic research results in the setting of high-risk pediatric cancer and inherited childhood diseases.

Methods: A validated 36-item questionnaire was mailed to participants in three large-scale genome research consortia examining attitudes toward receipt of genomic research results and the influence of certainty, severity, and onset of the condition, in addition to responsibilities to extended family and provision of results even after death of the proband.

Results: Of the 563 participants who were sent questionnaires, 362 (64%) responded.

The role of Frizzled-4 mutations in familial exudative vitreoretinopathy and Coats disease.

Aim: The aim of this study is to assess the role of Frizzled-4 (FZD4) in familial exudative vitreoretinopathy (FEVR) and Coats disease.

Methods: Tissue samples were collected for DNA extraction and automated DNA sequencing of the two coding exons of FZD4 in both directions. Cases carrying a FZD4 mutation and demonstrating extreme disease severity were selected for direct automated sequencing of all coding exons of LRP5, NDP and TSPAN12.

Severe retinopathy of prematurity associated with FZD4 mutations.

Purpose: To determine whether mutations in the FZD4 gene are a risk factor for developing severe ROP.

Methods: Three Canadian tertiary care centers recruited premature infants prospectively and retrospectively, and assigned affectation status based on the maximum degree of severity of ROP recorded in both eyes. Mutation screening of the FZD4 gene was performed using direct sequencing.

Application of homozygosity haplotype analysis to genetic mapping with high-density SNP genotype data.

Background: In families segregating a monogenic genetic disorder with a single disease gene introduction, patients share a mutation-carrying chromosomal interval with identity-by-descent (IBD). Such a shared chromosomal interval or haplotype, surrounding the actual pathogenic mutation, is typically detected and defined by multipoint linkage and phased haplotype analysis using microsatellite or SNP genotype data. High-density SNP genotype data presents a computational challenge for conventional genetic analyses.

Phenotypic overlap of familial exudative vitreoretinopathy (FEVR) with persistent fetal vasculature (PFV) caused by FZD4 mutations in two distinct pedigrees.

Purpose: To describe a severe familial exudative vitreoretinopathy (FEVR) phenotype seen in infancy that resembles persistent fetal vasculature (PFV) caused by mutations in the FZD4 gene in two pedigrees with high intrafamilial variability.

Methods: Three infants presented with features compatible with bilateral PFV. Eye examinations from the affected children and their relatives were reviewed retrospectively (follow-up:18 months-9 years).

Ocular features of CHARGE syndrome.

Purpose: To detail the presence and severity of ocular and cranial nerve abnormalities found in individuals with CHARGE syndrome in a distinct geographic area.

Methods: Nine individuals with CHARGE syndrome from Maritime Canada identified from a Canadian database were prospectively examined. Structural and sensorial defects associated with functional visual deficits were defined with ophthalmic and neurological evaluation.

Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy.

Familial exudative vitreoretinopathy (FEVR) is a hereditary ocular disorder characterized by a failure of peripheral retinal vascularization. Loci associated with FEVR map to 11q13-q23 (EVR1; OMIM 133780, ref. 1), Xp11.