Time filter

Source Type

London, United Kingdom

Glamuzina E.,Great Ormond Street Hospital for Children | Brown R.,University of Oxford | Hogarth K.,Great Ormond Street Hospital for Children | Saunders D.,Great Ormond Street Hospital for Children | And 8 more authors.
Journal of Inherited Metabolic Disease | Year: 2012

Pontocerebellar hypoplasia type 6 (PCH6) (MIM #611523) is a recently described disorder caused by mutations in RARS2 (MIM *611524), the gene encoding mitochondrial arginyl-transfer RNA (tRNA) synthetase, a protein essential for translation of all mitochondrially synthesised proteins. This case confirms that progressive cerebellar and cerebral atrophy with microcephaly and complex epilepsy are characteristic features of PCH6. Additional features of PCH subtypes 2 and 4, including severe dystonia, optic atrophy and thinning of the corpus callosum, are demonstrated. Congenital lactic acidosis can be present, but respiratory chain dysfunction may be mild or absent, suggesting that disordered mitochondrial messenger RNA (mRNA) translation may not be the only mechanism of impairment or that a secondary mechanism exists to allow some translation. We report two novel mutations and expand the phenotypic spectrum of this likely underdiagnosed PCH variant, where recognition of the characteristic neuroradiological phenotype could potentially expedite genetic diagnosis and limit invasive investigations. © SSIEM and Springer 2011. Source

Tadic V.,University College London | Hundt G.L.,University of Warwick | Keeley S.,University of Warwick | Rahi J.S.,University College London | Rahi J.S.,Ulverscroft Vision Research Group
Child: Care, Health and Development | Year: 2015

Background: Although the significant impact of visual disability in childhood has been widely recognized, children's own perspectives of living with a visual impairment have not been considered. We report the experiences of visually impaired (VI) children and young people aged 10-15 years about growing up with impaired sight. Methods: The participants were 32 VI children and young people, aged 10-15 years [visual acuity logarithm of minimum angle of resolution (LogMAR) worse than 0.51] recruited through National Health Service (NHS) paediatric ophthalmology and developmental vision clinics and 11 VI pupils aged 12-17 attending a specialist school for pupils with disabilities. Individual semi-structured interviews with participants captured their experiences of living with a visual impairment. A child-centred interview topic guide was developed from a literature review, observations at ophthalmology clinics, consultation with health and education professionals working with VI children and young people, and interviews and a focus group with VI pupils from the specialist school. Collaborative qualitative thematic analysis by three researchers identified emergent themes. NVivo software was used for coding the data. Results: Analysis identified six themes concerning living with a visual impairment: (i) social relationships, participation and acceptance; (ii) independence and autonomy; (iii) psychological and emotional well-being; (iv) aspirations and concerns about the future; (v) functioning - home, school and leisure; and (vi) treatment of eye condition. Key issues included: the importance of family and peer support; balancing independence, support and safety; the emotional burden and adjustment of living with a disability; concerns about education and job prospects in the future; functional restrictions and limitations; and ongoing management of the eye condition. Conclusions: The findings offer insights into the complex realities of living with visual impairment. They provide the basis for development of patient-reported outcome measures. They can also serve to help enrich the understanding of health professionals working with VI children and young people, potentially enabling them to better support them. © 2014 John Wiley & Sons Ltd. Source

Tadic V.,University College London | Cooper A.,Goldsmiths, University of London | Cumberland P.,University College London | Cumberland P.,Ulverscroft Vision Research Group | And 3 more authors.
PLoS ONE | Year: 2016

Purpose To report piloting and initial validation of the VQoL-CYP, a novel age-appropriate visionrelated quality of life (VQoL) instrument for self-reporting by children with visual impairment (VI). Methods Participants were a random patient sample of children with VI aged 10-15 years. 69 patients, drawn from patient databases at Great Ormond Street Hospital and Moorfields Eye Hospital, United Kingdom, participated in piloting of the draft 47-item VQoL instrument, which enabled preliminary item reduction. Subsequent administration of the instrument, alongside functional vision (FV) and generic health-related quality of life (HRQoL) selfreport measures, to 101 children with VI comprising a nationally representative sample enabled further item reduction and evaluation of psychometric properties using Rasch analysis. Construct validity was assessed through Pearson correlation coefficients. Results Item reduction through piloting (8 items removed for skewness and individual item response pattern) and validation (1 item removed for skewness and 3 for misfit in Rasch) produced a 35-item scale, with fit values within acceptable limits, no notable differential item functioning, good measurement precision, ordered response categories and acceptable targeting in Rasch. The VQoL-CYP showed good construct validity, correlating strongly with HRQoL scores, moderately with FV scores but not with acuity. Conclusions Robust child-appropriate self-report VQoL measures for children with VI are necessary for understanding the broader impacts of living with a visual disability, distinguishing these from limited functioning per se. Future planned use in larger patient samples will allow further psychometric development of the VQoL-CYP as an adjunct to objective outcomes assessment. © 2016 Tadić et al. 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. Source

Tadic V.,University College London | Tadic V.,Ulverscroft Vision Research Group | Cooper A.,Goldsmiths, University of London | Cumberland P.,University College London | And 3 more authors.
Ophthalmology | Year: 2013

Objective To develop a novel age-appropriate measure of functional vision (FV) for self-reporting by visually impaired (VI) children and young people. Design Questionnaire development. Participants A representative patient sample of VI children and young people aged 10 to 15 years, visual acuity of the logarithm of the minimum angle of resolution (logMAR) worse than 0.48, and a school-based (nonrandom) expert group sample of VI students aged 12 to 17 years. Methods A total of 32 qualitative semistructured interviews supplemented by narrative feedback from 15 eligible VI children and young people were used to generate draft instrument items. Seventeen VI students were consulted individually on item relevance and comprehensibility, instrument instructions, format, and administration methods. The resulting draft instrument was piloted with 101 VI children and young people comprising a nationally representative sample, drawn from 21 hospitals in the United Kingdom. Initial item reduction was informed by presence of missing data and individual item response pattern. Exploratory factor analysis (FA) and parallel analysis (PA), and Rasch analysis (RA) were applied to test the instrument's psychometric properties. Main Outcome Measures Psychometric indices and validity assessment of the Functional Vision Questionnaire for Children and Young People (FVQ-CYP). Results A total of 712 qualitative statements became a 56-item draft scale, capturing the level of difficulty in performing vision-dependent activities. After piloting, items were removed iteratively as follows: 11 for high percentage of missing data, 4 for skewness, and 1 for inadequate item infit and outfit values in RA, 3 having shown differential item functioning across age groups and 1 across gender in RA. The remaining 36 items showed item fit values within acceptable limits, good measurement precision and targeting, and ordered response categories. The reduced scale has a clear unidimensional structure, with all items having a high factor loading on the single factor in FA and PA. The summary scores correlated significantly with visual acuity. Conclusions We have developed a novel, psychometrically robust self-report questionnaire for children and young people - the FVQ-CYP - that captures the functional impact of visual disability from their perspective. The 36-item, 4-point unidimensional scale has potential as a complementary adjunct to objective clinical assessments in routine pediatric ophthalmology practice and in research. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article. © 2013 by the American Academy of Ophthalmology Published by Elsevier Inc. Source

Henderson R.H.,Professorial Unit | Henderson R.H.,University College London | Mackay D.S.,University College London | Li Z.,University College London | And 14 more authors.
British Journal of Ophthalmology | Year: 2011

Objectives: To identify CRB1 mutations in a large cohort of patients with recessive retinal dystrophies and to document the retinal phenotype and visual prognosis. Design: A hospital-based cross-sectional study of children and adults with recessive retinal dystrophies. Participants: Three hundred and six patients with Leber congenital amaurosis (LCA), early-onset childhood retinal dystrophy or juvenile onset retinitis pigmentosa were recruited to the study and gave blood samples for molecular genetic analysis. Methods: A detailed clinical examination was performed, including: logMAR visual acuity, refraction, Goldmann visual fields, slit-lamp biomicroscopy, fundus photography, autofluorescence imaging and optical coherence tomography. The results of electrophysiology testing were available in all patients. DNA was obtained for molecular genetic analysis. Initial screening for mutations was performed using the LCA chip. Patients who had one or more CRB1 mutations identified on the chip, and other patients whose phenotype suggested a CRB1 genotype, underwent direct sequencing. In addition, consanguineous families segregating recessive RP underwent a whole genome scan using Affymetrix gene chips, and affected family members showing linkage to the RP12 locus underwent sequencing of the CRB1 gene. Main outcome measures: Identification of patients with mutations in CRB1 and detailed documentation of the clinical phenotype. Results: Mutations in CRB1, including 17 novel mutations, were identified in 41 patients from 32 families. The authors identified both disease mutations in 34 patients from 26 families, and these patients underwent detailed phenotyping. Common phenotypic features included hypermetropic refractive error, nummular pigmentation at the level of the RPE and increased retinal thickness on optical coherence tomography. Most patients had a clinical and electrophysiological phenotype consistent with a diagnosis of LCA or rod - cone dystrophy, but three patients had electroretinogram evidence of cone - rod degeneration. A minority of patients developed peripheral retinal telangiectasia, which in some cases led to seclusio pupillae and angle-closure glaucoma. Conclusion: Mutations in CRB1 are associated with a range of recessively inherited retinal dystrophies, including LCA, childhood- and juvenile-onset rod - cone and cone - rod dystrophies. Although the phenotype is usually severe, in milder cases there is a window of opportunity for therapeutic intervention in early childhood. Source

Discover hidden collaborations