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Childhood-onset Leber hereditary optic neuropathy
  1. Anna Majander1,2,3,
  2. Richard Bowman4,
  3. Joanna Poulton5,
  4. Richard J Antcliff6,
  5. M Ashwin Reddy2,
  6. Michel Michaelides1,2,
  7. Andrew R Webster1,2,
  8. Patrick F Chinnery7,8,9,
  9. Marcela Votruba10,
  10. Anthony T Moore1,2,11,
  11. Patrick Yu-Wai-Man1,2,7,12
  1. 1UCL Institute of Ophthalmology, London, UK
  2. 2Moorfields Eye Hospital, London, UK
  3. 3Department of Ophthalmology, Helsinki University Hospital, and University of Helsinki, Helsinki, Finland
  4. 4Great Ormond Street Hospital, London, UK
  5. 5Nuffield Department of Obstetrics & Gynaecology, University of Oxford, Oxford, UK
  6. 6Department of Ophthalmology, Royal United Hospital, Bath, UK
  7. 7Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK
  8. 8Medical Research Council Mitochondrial Biology Unit, Cambridge, UK
  9. 9Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge, UK
  10. 10School of Optometry and Vision Sciences, Cardiff University and Cardiff Eye Unit, University Hospital Wales, Cardiff, UK
  11. 11Ophthalmology Department, UCSF School of Medicine, San Francisco, California, USA
  12. 12Newcastle Eye Centre, Royal Victoria Infirmary, Newcastle upon Tyne, UK
  1. Correspondence to Dr Anna Majander, UCL Institute of Ophthalmology and Moorfields Eye Hospital, 162 City Road, London, EC1V 2PD London, UK; and Department of Ophthalmology, Helsinki University Hospital, and University of Helsinki, P.O. Box 220, Helsinki FI-00029, Finland; anna.majander{at}hus.fi

Abstract

Background The onset of Leber hereditary optic neuropathy (LHON) is relatively rare in childhood. This study describes the clinical and molecular genetic features observed in this specific LHON subgroup.

Methods Our retrospective study consisted of a UK paediatric LHON cohort of 27 patients and 69 additional cases identified from a systematic review of the literature. Patients were included if visual loss occurred at the age of 12 years or younger with a confirmed pathogenic mitochondrial DNA mutation: m.3460G>A, m.11778G>A or m.14484T>C.

Results In the UK paediatric LHON cohort, three patterns of visual loss and progression were observed: (1) classical acute (17/27, 63%); (2) slowly progressive (4/27, 15%); and (3) insidious or subclinical (6/27, 22%). Diagnostic delays of 3–15 years occurred in children with an insidious mode of onset. Spontaneous visual recovery was more common in patients carrying the m.3460G>A and m.14484T>C mutations compared with the m.11778G>A mutation. Based a meta-analysis of 67 patients with available visual acuity data, 26 (39%) patients achieved a final best-corrected visual acuity (BCVA) ≥0.5 Snellen decimal in at least one eye, whereas 13 (19%) patients had a final BCVA <0.05 in their better seeing eye.

Conclusions Although childhood-onset LHON carries a relatively better visual prognosis, approximately 1 in 5 patients will remain within the visual acuity criteria for legal blindness in the UK. The clinical presentation can be insidious and LHON should be considered in the differential diagnosis when faced with a child with unexplained subnormal vision and optic disc pallor.

  • Child health (paediatrics)
  • Optic Nerve
  • Vision
  • Genetics
  • Diagnostic tests/Investigation

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Footnotes

  • Contributors Research design: AM, MV, ATM, PY-W-M. Data acquisition and/or research execution: AM, RB, JP, RJA, MAR, MM, ARW, MV, ATM, PY-W-M. Data analysis and/or interpretation: AM, PFC, MV, ATM, PY-W-M. Manuscript preparation: AM, PY-W-M.

  • Funding This research was supported by the National Institute for Health Research Rare Diseases Translational Research Collaboration (NIHR RD-TRC) and the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital National Health Service Foundation Trust and UCL Institute of Ophthalmology, the NIHR Moorfields Clinical Research Facility. AM receives funding from Suomen Silmätutkimusseura ry:n Apurahasäätiö (Finland). MV and PY-W-M receive funding from Fight for Sight (UK). ATM, MV, PFC and PY-W-M receive funding from the UK National Institute of Health Research (NIHR) as part of the Rare Diseases Translational Research Collaboration. PY-W-M is supported by a Clinician Scientist Fellowship Award (G1002570) from the Medical Research Council (UK). PFC is a Wellcome Trust Senior Fellow in Clinical Science (101876/Z/13/Z), and a UK NIHR Senior Investigator, who receives support from the Medical Research Council Mitochondrial Biology Unit (MC_UP_1501/2), the Wellcome Trust Centre for Mitochondrial Research (096919Z/11/Z), the Medical Research Council (UK) Centre for Translational Muscle Disease (G0601943). JP was funded by the MRC (MR/J010448/1) and the Wellcome Trust (0948685/Z/10/Z) and has salary support from the NHS specialised Services Rare Mitochondrial Disorders Service.

  • Competing interests PY-W-M holds a consultancy agreement with GenSight Biologics (Paris, France).

  • Ethics approval The ethics committee at Moorfields Eye Hospital, London, UK.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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