LHON needs to be genetically diagnosed and the idebenone effect quantified (original) (raw)
Related papers
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...
Influence of Mutation Type on Clinical Expression of Leber Hereditary Optic Neuropathy
American Journal of Ophthalmology, 2006
PURPOSE: The aim of this research was to determine the molecular factors of influence on the clinical expression of Leber hereditary optic neuropathy (LHON), which might aid in counseling LHON patients and families. The prevalence of LHON in the Dutch population was determined. • DESIGN: Observational, retrospective population cohort study. • METHODS: The clinical characteristics of LHON patients of 25 families, previously described in 1963, were reevaluated. The mutation and haplotype were determined in the DNA of one affected LHON patient per family. The genotype of their relatives could be deducted, enabling us to evaluate retrospectively the genotypephenotype correlation. The prevalence of LHON was determined on the basis of anamnestic evaluation of patients in 1963 and by using population registers of that period. • RESULTS: The LHON mutation does not influence disease penetrance (50% in male subjects; 10% to 20% in female subjects). More than half of the patients with the 14484 mutation exhibit a partial recovery of vision, regardless of the acuteness of disease onset (P ؍ .001), whereas only 22% of the 11778 carriers and 15.4% of the 3460 carriers recovered. The recovery did not take place within the first year after onset and was uncommon after four years. The onset of LHON is in general very acute but might be more gradual in 11778 carriers and in children. The calculated prevalence of LHON in the Dutch population (1/39,000) is very likely an underestimation caused by a selection bias of familial cases in the original study. • CONCLUSIONS: The LHON genotype influences the recovery of vision and disease onset but is unrelated to age, acuteness of onset, or gender. The genotype does not influence disease penetrance. Children might exhibit a slower onset of disease. (Am J Ophthalmol 2006;141: 676 -682.
Documenta Ophthalmologica, 2000
Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease, associated with mitochondrial DNA (mtDNA) point mutations and characterized by bilateral, usually sequential, rapid loss of central vision. The purpose of this study was to investigate electrophysiologically a small cohort of members from an extensive Brazilian family affected by LHON. Pattern-reversal visual evoked potentials (PVEP), and full-field electroretinograms (ERG) were performed on the four index members, all carrying the 11778 homoplasmic mtDNA mutation. They were a 14-year-old recently affected male, his unaffected mother, and her two affected brothers. The three affected members all had bilateral profound visual loss with visual acuities that ranged from 20/250 to CF, cecocentral defects, and severe dyschromatopsia (by FM-100). The unaffected (carrier) female had normal visual acuities, visual fields and color discrimination. Severely prolonged P100 latencies and decreased N75-P100 peak amplitudes were found in pattern-reversal VEPs for three affected members. Normal PVEP responses were found in the carrier female. Rod and cone ERG responses were normal in two affected members, but both the carrier mother and her affected son showed reduced peak-to-peak amplitude for single-flash cone response and 30 Hz flicker, with normal b-wave implicit times. Thus, optic nerve function, evaluated by PVEP, was severely reduced in LHON affected members and normal in the carrier female. However, reduced ERG cone responses suggest that LHON can also affect retinal elements, even in the absence of fundus and other clinical changes that constitute the full and classical expression of 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