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At least 37 records · Page 2Linked to original sources
PubMed2004

Characteristic retinal atrophy with secondary "inverse" optic atrophy identifies vigabatrin toxicity in children.

OBJECTIVE: To describe the clinical pattern of retinal atrophy in children caused by the anticonvulsant vigabatrin. DESIGN: An interventional case series report. PARTICIPANTS: One hundred thirty-eight patients, mainly infants, were evaluated regularly for evidence of possible vigabatrin toxicity in the Eye and Neurology clinics at the Hospital for Sick Children, Toronto. METHOD: Sequential clinical and electroretinographic (International Society for Clinical Electrophysiology of Vision standards) evaluations every 6 months. MAIN OUTCOME MEASURES: Presence of recognizable retinal and optic atrophy in the presence of abnormal electroretinogram (ERG) and other clinical findings. RESULTS: Three children being treated for seizures with vigabatrin showed definite clinical findings of peripheral retinal nerve fiber layer atrophy, with relative sparing of the central or macular portion of the retina and relative nasal optic nerve atrophic changes. Some macular wrinkling was evident in 1 case. Progressive ERG changes showing decreased responses, especially the 30-Hz flicker response, supported the presence of decreased retinal function. CONCLUSIONS: A recognizable and characteristic form of peripheral retinal atrophy and nasal or "inverse" optic disc atrophy can occur in a small number of children being treated with vigabatrin. The changes in superficial light reflexes of the retina in children facilitate the clinical recognition of nerve fiber layer atrophy. The macula is relatively spared, although superficial retinal light reflexes indicating wrinkling of the innermost retina suggest early macular toxicity as well. Because these changes are accompanied by electrophysiologic evidence of retinal dysfunction, discontinuation of vigabatrin should be strongly considered.

Adolescent↗
PubMed1992

An aetiological profile of optic atrophy.

484 cases of optic atrophy were studied for the distribution pattern and significance of various etiological factors in different age groups of both sexes. Bilateral optic atrophy was found to be two and a half times as common as unilateral optic atrophy. Intracranial neoplasm (29.5%) was the most frequent known cause of bilateral optic atrophy in either sex and the most common tumor was chromophobe adenoma (48% of intracranial tumors) with highest incidence over 20 years of age. Craniopharyngioma was the most frequent tumor responsible for bilateral optic atrophy before 20 years of age. Intracranial glioma also emerged as an important cause of bilateral optic atrophy. Head injury due to road accidents and periocular trauma were the most common causes of unilateral optic atrophy in males, whereas no definite factor could be elucidated in unilateral optic atrophy in females. Vascular factors were the usual cause of optic atrophy after 40 years of age, highlighting the significance of thorough systemic evaluation.

Adolescent↗
PubMed2006

Novel mutations in the OPA1 gene and associated clinical features in Japanese patients with optic atrophy.

PURPOSE: Autosomal dominant optic atrophy (ADOA) is characterized by symmetrical bilateral optic atrophy associated with reduced corrected visual acuity (VA), central or centrocecal scotoma, and color vision disturbances. The disease is genetically heterogeneous, and the OPA1 gene has been identified as the only causative gene. The aims of this study were to identify and report mutations in the OPA1 gene in Japanese patients with ADOA and to describe the clinical features associated with the mutations. DESIGN: Molecular genetic study and observational case reports. PARTICIPANTS: Nine unrelated Japanese families with optic atrophy and 8 isolated cases of optic atrophy. METHODS: Genomic DNA was extracted from peripheral leukocytes, and all exons containing the open reading frame of the OPA1 gene and the flanking intron splice sites were sequenced directly. Complete ophthalmologic examinations were performed. MAIN OUTCOME MEASURES: Direct sequencing of the OPA1 gene and clinical evaluations including VA, visual field, color vision, and disc appearance. RESULTS: Ten different heterozygous mutations, including 6 novel mutations, were detected in the OPA1 gene. The identified mutations included 5 deletions/insertions (c.2061delA, c.2098_2103delCTTAAA, c.2538insT, c.2591insC, and c.2708_2711delTTAG), 4 nonsense mutations (c.112C>T [p.R38X], c.181C>T [p.Q61X], c.946A>T [p.R316X], and c.2713C>T [p.R905X]), and 1 missense mutation (c.1635C>A [p.S545R]). The most common mutation in Caucasians (c.2708_2711delTTAG) was found in 3 unrelated families, suggesting that it is a mutational hot spot. We detected an OPA1 mutation in 8 of 9 familial cases of optic atrophy and in 4 of 8 cases that were initially considered to be sporadic from the patients' family histories. Examinations of family members of 2 sporadic probands revealed the existence of other family members with the OPA1 mutations whose phenotype was very mild or within normal limits. This indicates that patients with ADOA sometimes seem to be sporadic because of the extensive variation in the phenotype or, alternatively, a low penetrance of ADOA. CONCLUSIONS: OPA1 gene mutations are causative in most familial cases of ADOA in Japanese. Sporadic cases of optic atrophy frequently may be caused by OPA1 mutations in the Japanese population. Molecular genetic examinations are useful in determining the hereditary patterns in some cases of optic atrophy.

Adult↗
PubMed1991

Optic atrophy in Leber hereditary optic neuroretinopathy is probably determined by an X-chromosomal gene closely linked to DXS7.

Leber hereditary optic neuroretinopathy (LHON) is a maternally inherited disease, probably transmitted by mutations in mtDNA. The variation in the clinical expression of the disease among family members has remained unexplained, but pedigree data suggest an involvement of an X-chromosomal factor. We have studied genetic linkage of the liability to develop optic atrophy to 15 polymorphic markers on the X chromosome in six pedigrees with LHON. The results show evidence of linkage to the locus DXS7 on the proximal Xp. Tight linkage to the other marker loci was excluded. Multipoint linkage analysis placed the liability locus at DXS7 with a maximum lod score (Zmax) of 2.48 at a recombination fraction (theta) of .0 and with a Zmax - 1 support interval theta = .09 distal to theta = .07 proximal of DXS7. No evidence of heterogeneity was found among different types of families, with or without a known mtDNA mutation associated with LHON.

Adult↗
PubMed2006

Structural model of the OPA1 GTPase domain may explain the molecular consequences of a novel mutation in a family with autosomal dominant optic atrophy.

Autosomal dominant optic atrophy (ADOA) is the most frequent hereditary optic neuropathy. Three loci have been reported for ADOA: a major locus, harboring all identified mutations to date, maps to 3q28 (OPA1), a second locus is linked to 18q12.2-q12.3 (OPA4) and a third locus on 22q12.1-q13.1 (OPA5) has been reported recently. We describe a six-generation Iranian family in which optic atrophy runs as an autosomal dominant trait with an age of onset at 14-15years. We performed linkage analysis with markers mapping to 3q28 and 18q12.2-q12.3 and found linkage to 3q28. Subsequent sequencing of OPA1 identified a novel heterozygous missense mutation (c.1313A>G) replacing aspartic acid by glycine (p.D438G) in the GTPase domain of OPA1. Interestingly, another missense mutation at the same position (c.1313A>T, D438V) has been reported before in two unrelated German families, indicating a possible mutation hot spot. Further evidence supporting the importance of D438 is its conservation from human to acoelomata. OPA1 is believed to be the human orthologue of yeast MGM1, a dynamin-related protein required for the integrity of mitochondrial DNA. Homology modeling of the OPA1 GTPase domain revealed extensive structural similarity to the Dictyostelium dynamin A GTPase domain and showed that D438 may interact with residues of the G1 and the G4 motifs, which are crucial in coordinating GTP. Based on this analysis, we propose a mechanism which explains the gradual decline of vision in ADOA patients with OPA1 mutations at position 438.

Adolescent↗
PubMed1995

No evidence of genetic heterogeneity in dominant optic atrophy.

Autosomal dominant optic atrophy (OPA, MIM 165500) is an eye disease causing a variable reduction of visual acuity with an insidious onset in the first six years of life. It is associated with a central scotoma and an acquired blue-yellow dyschromatopsia. A gene for dominant optic atrophy (OPA1) has recently been mapped to chromosome 3q in three large Danish pedigrees. Here, we confirm the mapping of OPA1 to chromosome 3q28-qter by showing close linkage of the disease locus to three recently reported microsatellite DNA markers in the interval defined by loci D3S1314 and D3S1265 in four French families (Zmax = 5.13 at theta = 0 for probe AFM 308yf1 at locus D3S1601). Multipoint analysis supports the mapping of the disease gene to the genetic interval defined by loci D3S1314 and D3S1265. The present study provides three new markers closely linked to the disease gene for future genetic studies in OPA.

Chromosome Mapping↗
PubMed1983

Histopathology of eye, optic nerve and brain in a case of dominant optic atrophy.

Histopathology of eye, optic nerve and brain was performed in a patient with typical signs and symptoms of dominant optic atrophy. He belonged to a previously-reported family of 152 members in which optic atrophy was demonstrable in 14 persons, and probably present in a further 8 cases. In the eyes, fibrosis of the retinal ganglion cell layer and disc was found. Ultrastructural examination showed a few remaining cells in this layer, heavy fibrosis and in particular a highly condensed inner limiting membrane. The optic nerves, the optic chiasm and optic tracts showed an increased content of collagen tissue and a decreased number of neurofibrils and myelin sheaths. In the lateral geniculate body there was massive loss of ganglion cells, fibrillary gliosis and a great quantity of fine granular lipid in the cytoplasm of the ganglion cells. No changes in the calcarine cortex were observed. Examination of the intracranial part of both vestibulocochlear nerves showed a decreased number of neurofibrils and myelin sheaths. It is concluded that the histopathological changes of the visual system are similar to those in Leber's disease, but less pronounced. The study confirms earlier theories that dominant optic atrophy is a primary degeneration of the ganglion cell layer in the retina, with ascending optic atrophy.

Aged↗
PubMed2005

Optic atrophies in metabolic disorders.

Optic nerve involvement in metabolic disorders often results from apoptosis of cells that form or support the optic nerve, the retinal ganglion cell (RGC) axons, the myelin-forming oligodendrocytes, or the supporting vascular system. Given their high energy demands and the long course of their axons, RGCs are particularly sensitive to intracellular metabolic defects. Defects in energy metabolism, formation of reactive oxygen species, and storage of metabolites can all cause apoptosis of RGCs, decreased myelin formation of oligodendrocytes and increased pressure on the optic nerve. Clinically, the loss of RGC axons manifests as pale optic nerves. In general, the ophthalmologist can identify the underlying cause of an optic atrophy by careful examination, neuro-imaging, and family history. In some cases, however, the diagnosis proves elusive. In these instances, and especially when optic atrophy is accompanied by other systemic involvement, a metabolic disorder should be considered. Here, we review the underlying mechanisms of optic atrophy and its significance in metabolic disorders. Early identification of optic atrophy aids the diagnosis and subsequent management of the underlying condition, including anticipation of symptoms, genetic counseling, and possible therapeutic interventions. For many metabolic disorders, molecular testing is available.

Humans↗
PubMedDate not supplied

Is all nondefinable optic atrophy Leber's hereditary optic neuropathy?

Leber's hereditary optic neuropathy has been considered a bilateral, sequential hereditary optic neuropathy occurring overwhelmingly in young men. Until recently the diagnosis has been based on clinical criteria: severe loss of vision associated with central scotomas and classic ophthalmoscopic findings (circumpapillary telangiectatic microangiopathy, pseudoedema of the disk with absence of staining on fluorescein angiography, tortuous vessels in the early stages and eventually optic disk pallor). In 1988 a genetic mutation associated with Leber's hereditary optic neuropathy affecting mitochondrial DNA was recognized. Subsequently other mutations have been discovered as well. The ability to identify these patients technically has allowed us to recognize cases that do not fit our previous clinical criteria. One such case is presented and the question asked is whether the findings are related to the clinical course.

Child↗
PubMed2004

Complete mitochondrial DNA sequence analysis in a family with early-onset dystonia and optic atrophy.

The combination of optic atrophy and dystonia has been etiologically associated with mitochondrial DNA (mtDNA) mutations. We report here on the complete mtDNA sequence from the proband of a consanguineous family exhibiting "mitochondrial-like" optic atrophy and dystonia. A candidate tRNA(Gly) mutation was identified that was unique to the family. However, the mutation was homoplasmic in both affected and unaffected family members and we were unable to demonstrate a biochemical defect in patient mitochondria. Hence, it is unlikely that a mtDNA mutation accounts for the phenotype in this family.

Adult↗
PubMed1976

[Hereditary optic atrophies].

Congenital or infantile autosomal recessive optic atrophy is rare. The autosomal recessive syndrome of optic atrophy associated with diabetes is less rare. Dominant juvenile optic atrophy occurs frequently. Behr's heredo-familial optic atrophy, with its neurological mainfestations and its recessive autosomal inheritance, is rare. Sex-linked optic atrophy is exceptional. Leber's optic neuritis occurs frequently. Its heredity is apparently sex-linked, but no classical mode of transmission can be applied. Cytoplasmic heredity is the most probable.

Diabetes Complications↗
PubMed2000

MRI of the intraorbital optic nerve in patients with autosomal dominant optic atrophy.

Measurements of the intraorbital optic nerve were made using high-resolution coronal MRI in 10 adults with autosomal dominant optic atrophy. Comparisons were made with previous studies of 10 normal adult subjects. The cross-sectional diameters of the optic nerve and the perineural subarachnoid space were measured and a ratio of there diameters at anterior, mid and posterior positions along the optic nerve was determined. We found a statistically significant difference in the mean optic nerve: sheath ratio between the control group and patients with autosomal dominant optic atrophy. At anterior, mid and posterior locations along the optic nerve it is significantly smaller in patients with optic atrophy. We have demonstrated that the loss of ganglion cells, previously documented in dominant optic atrophy, is associated with a significant loss of optic nerve tissue and thinning of the nerve along its length.

Case-Control Studies↗
PubMed1990

[Ophthalmological anomalies of the GAPO syndrome (growth retardation, alopecia, pseudo-anodontia, optic atrophy). Apropos of a case].

G.A.P.O. syndrome is a rare autosomal recessive disorder whose main manifestations are growth retardation, alopecia, pseudo-anodontia, and optic atrophy. Optic atrophy has been reported in 30% of affected patients, along with other optic disc and ophthalmological abnormalities, but their causes remain unclear. We report here the ophthalmological findings in a three-year-old girl suffering from typical G.A.P.O. syndrome with ocular abnormalities and bilateral optic atrophy. Physiopathogenic hypotheses are discussed, especially concerning optic disc alterations which are probably due to intraocular hypertension.

Abnormalities, Multiple↗