Childhood-onset Leber hereditary optic neuropathy.
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.



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.



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.



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.
UCL Institute of Ophthalmology, London, UK.|Moorfields Eye Hospital, London, UK.|Department of Ophthalmology, Helsinki University Hospital, and University of Helsinki, Helsinki, Finland.
Anna
A
Majander
Great Ormond Street Hospital, London, UK.
Richard
R
Bowman
Nuffield Department of Obstetrics & Gynaecology, University of Oxford, Oxford, UK.
Joanna
J
Poulton
Department of Ophthalmology, Royal United Hospital, Bath, UK.
Richard J
RJ
Antcliff
Moorfields Eye Hospital, London, UK.
M Ashwin
MA
Reddy
UCL Institute of Ophthalmology, London, UK.|Moorfields Eye Hospital, London, UK.
Michel
M
Michaelides
UCL Institute of Ophthalmology, London, UK.|Moorfields Eye Hospital, London, UK.
Andrew R
AR
Webster
Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.|Medical Research Council Mitochondrial Biology Unit, Cambridge, UK.|Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge, UK.
Patrick F
PF
Chinnery
School of Optometry and Vision Sciences, Cardiff University and Cardiff Eye Unit, University Hospital Wales, Cardiff, UK.
Marcela
M
Votruba
UCL Institute of Ophthalmology, London, UK.|Moorfields Eye Hospital, London, UK.|Ophthalmology Department, UCSF School of Medicine, San Francisco, California, USA.
Anthony T
AT
Moore
UCL Institute of Ophthalmology, London, UK.|Moorfields Eye Hospital, London, UK.|Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.|Newcastle Eye Centre, Royal Victoria Infirmary, Newcastle upon Tyne, UK.
Patrick
P
Yu-Wai-Man
D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D029242:Optic Atrophy, Hereditary, Leber / Q000453:epidemiology* / Q000235:genetics; D011379:Prognosis; D012189:Retrospective Studies; D006113:United Kingdom / Q000453:epidemiology; D014792:Visual Acuity
Child health (paediatrics); Diagnostic tests/Investigation; Genetics; Optic Nerve; Vision