Childhood-Onset Leber Hereditary Optic Neuropathy: Particular Features (original) (raw)
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Childhood-onset Leber hereditary optic neuropathy
The British journal of ophthalmology, 2017
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-...
Leber Hereditary Optic Neuropathy: Case Report and Literature Review
Cureus, 2020
Leber hereditary optic neuropathy (LHON) is a genetic condition that typically presents with unilateral, painless, sub-acute central vision loss followed by contralateral vision loss after a few weeks to months. It is a rare disease that typically affects young adults-men more than women-and is a relatively common cause of blindness. It is due to a mutation in mitochondrial DNA (mtDNA). The majority (more than 95%) of patients have one of three mtDNA point mutations: m.14484T→C, m.3460G→A, or m.11778G→A. These mutations lead to disruption of the mitochondrial respiratory chain activating pro-apoptotic pathways. For reasons unknown, this insult tends to affect the retinal ganglion cells more than any other cell in the body, leading to the disease state. Due to its low prevalence in the United States (1:50,000), this diagnosis is often overlooked, misdiagnosed, and mismanaged, which may exacerbate symptoms. It is essential then for physicians to recognize the presentation of and understand the diagnostic work-up for LHON. In this case report, we present the diagnostic challenges of a patient who presented with progressive vision loss, discuss the various differential diagnoses, review the literature on LHON, and propose an explanatory model for vision loss in patients with LHON.
Leber hereditary optic neuropathy — Historical report in comparison with the current knowledge
Gene, 2015
Leber hereditary optic neuropathy (LHON) is a genetic, maternally inherited disease caused by point mutations in 21 the mitochondrial genome. LHON patients present with sudden, painless and usually bilateral loss of vision 22 caused by optic nerve atrophy. The first clinical description of the disease was made by Theodor Leber, a German 23 ophthalmologist, in 1871. Here we present his thorough notes about members of four families and their pedi-24 grees. We also provide insights into the current knowledge about LHON pathology, genetics and treatment in 25 comparison with Leber's findings. 26
Leber's hereditary optic neuropathy: correlations between mitochondrial genotype and visual outcome
Journal of Medical Genetics, 1994
Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease associated with mitochondrial DNA (mtDNA) mutations. We describe the distribution of seven different mtDNA mutations and the clinical findings in 334 LHON patients belonging to 29 families. Mutations described only in LHON at nucleotide positions 11778, 3460, and 14484 were found in 15, two, and nine families respectively. In three families none of these mutations was found. Mutations described in LHON but also in controls at nucleotide positions 15257, 13708, 4917, and 4216 were found in one, 10, three and 12 families respectively. Combinations of mtDNA mutations were found in most families. The patient population mainly consisted of 79-2% to 89'5% males except for one family with only 10 of 17 patients being males (58-9%, p-0 036). In 11 families only the 11778 mutation was found; in this group (WX) the affected males had a mean age of onset of 29-2 years and a mean visual outcome of 0-113. In seven families the 14484, 13708, and 4216 mutations were found; in this group (MA) the affected males had a mean age of onset of 22-0 years and a mean visual outcome of 0-442. In two families no mutation was found at all; in this group (YX) the affected males had a mean age of onset of 18-9 years and a mean visual outcome of 0 167. The mean age of onset in the WX group is significantly higher than in the MA group (p< 0-01) and in the YX group (p001).
Brain, 1995
One hundred and seven patients from 79 families were defined as having Leber's hereditary optic neuropathy (LHON) by the presence of one of the mitochondrial DNA (mtDNA) mutations at positions 11778 (60 families), 3460 (seven families) or 14484 (12 families). Only half of the 11778 index patients had a history of similarly affected relatives; this proportion was higher with the 3460 (71%) and 14484 (100%) mutations. The ratios of affected male to female patients were 2.5:1 (11778), 2:1 (3460), and 5.7:1 (14484). Detailed clinical data were available for 79 patients from 55 families. Visual loss developed between the ages of 11 and 30 years in 69%, with a range of 6-62 years, and no significant differences between mutation groups or males and females. It was bilateral in all but two patients, to a median of counting fingers with a central scotoma, developing simultaneously in 22% and sequentially in 78%, with a median inter-eye delay of 8 weeks, and progressing in each eye over a period of 4-6 weeks. Nineteen patients had pain in an affected eye or on eye movements, and four experienced Uhthoff's phenomenon. Retinal microangiopathy was uncommon after 6 months from onset and was not detected in 36% of patients examined within 3 months of visual loss; the microangiopathy was particularly uncommon in the 14484 group. There was no difference in the overall visual outcome between the 11778 and 3460 groups with median final visual acuities of 1/60 and 3/60, respectively. Particularly severe visual loss occurred in one-third of women with the 11778 mutation, to vague perception of light or no perception of light in at least one eye. A multiple sclerosis-like illness was observed in 45% of females with the 11778 mutation. Prognosis was substantially better in the 14484 patients, with recovery to a final visual acuity of at least 6/24, in 71% of patients. Good visual outcome was strongly correlated with age at onset, all those with onset before 20 years having a final visual acuity better than 6/24 as opposed to only 2 out of 6 with later onset. Improvement in vision occurred as long as 4 years after onset. High alcohol and tobacco consumption, cranial or ocular trauma, young or old age at presentation, co-existing neurological disease, and recent childbirth with post-partum haemorrhage, all contributed to diagnostic difficulties in this series, usually in the absence of a family history. These problems were resolved by mtDNA analysis.
Leber's Hereditary Optic Neuropathy: A Case Report
The Kaohsiung Journal of Medical Sciences, 2003
LHON is characterised by bilateral asynchronous visual loss in young adults. This type of neuropathy is related to mitochondrial DNA mutation and therefore is maternally inherited. Males are predominantly affected but they do not transmit the disease to their offspring. Clinical picture-although characteristic-is not impressive. At the beginning of the disease, there is a large discrepancy between the symptoms and signs. In contrast to marked central visual loss, the only visible sign is retinal teleangiectatic microangiopathy in the peripapillary region. Fluorescein angiography shows intact capillary network without leakage disproving its inflammatory nature.
BMC Neurology
Background: Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by visual loss consequent to optic nerve atrophy. In some cases, LHON is associated with heterogeneous neurological extraocular manifestations and is referred to as "Leber plus disease"; rarely it is associated with a multiple sclerosis (MS)-like syndrome known as Harding disease, but no pediatric extraocular acute spinal onset is reported. Case presentation: We describe the case of a 5-year-old girl carrying the G3460A mtDNA mutation who was referred to clinical examination for bilateral upper and lower limb weakness with no sign of optic neuropathy. Spinal cord MRI showed hyperintense signal alterations in T2-weighted and restricted diffusion in DWI sequences in the anterior portion of the cervical and dorsal spinal cord resembling a spinal cord vascular injury. No association between this mutation and pediatric spinal cord lesions has previously been reported. Alternative diagnostic hypotheses, including infective, ischemic and inflammatory disorders, were not substantiated by clinical and instrumental investigations. Conclusions: Our case reports a novel pediatric clinical manifestation associated with the m.3460G > A mtDNA mutation, broadening the clinical spectrum of this disease. Early identification of new cases and monitoring of carriers beginning in childhood is important to prevent neurological deterioration and preserve long-term function.
Genetics and treatment of Leber' s hereditary optic neuropathy (LHON)
2014
The current concepts about Leber's hereditary optic neuropathy (LHON) and mitochondrial connection are very difficult to understand completely. Even after twenty years of clinical studies, it is still difficult to completely explain how LHON mutations cause damage to the optic nerve or why particularly the optic nerve is at risk, and the information about mitochondria, the mitochondrial genome, the metabolism of the optic nerve and the phenotypic variability of LHON are still being discussed. We cannot fully explain the incomplete penetrance or the male predominance of LHON, the typical onset in young adults or the bilaterality of visual loss. Evidence points to abnormalities of the mitochondria as the direct or indirect cause of LHON. Primary LHON mutations definitely are not present in every family with the LHON phenotype and multigenerational maternal inheritance. They may be present in only a minority of patients with LHON phenotype without a clear family history. Therefore...