A gene for X-linked idiopathic congenital nystagmus (NYS1) maps to chromosome Xp11.4-p11.3.
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Congenital nystagmus (CN) is a common oculomotor disorder (frequency of 1/1,500 live births) characterized by bilateral uncontrollable ocular oscillations, with onset typically at birth or within the first few months of life. This condition is regarded as idiopathic, after exclusion of nervous and ocular diseases. X-linked, autosomal dominant, and autosomal recessive modes of inheritance have been reported, but X-linked inheritance is probably the most common. In this article, we report the mapping of a gene for X-linked dominant CN (NYS1) to the short arm of chromosome X, by showing close linkage of NYS1 to polymorphic markers on chromosome Xp11.4-p11.3 (maximum LOD score of 3.20, over locus DXS993). Because no candidate gene, by virtue of its function, has been found in this region of chromosome Xp, further studies are required, to reduce the genetic interval encompassing the NYS1 gene. It is hoped that the complete gene characterization will address the complex pathophysiology of CN. (+info)
Vertical or asymmetric nystagmus need not imply neurological disease.
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AIM: To indicate that congenital idiopathic nystagmus (CIN) and sensory defect nystagmus (SDN) can be vertical or asymmetric in some children. METHODS: Of 276 children presenting with nystagmus for electrophysiological testing, 14 were identified as having CIN or SDN, yet had a nystagmus which was either vertical (n=11) or horizontal asymmetric (n=3). Flash electroretinograms and flash and pattern visual evoked potentials (VEPs) were recorded in all patients. Eye movement assessment, including horizontal optokinetic nystagmus (OKN) testing, was carried out in 11/14 patients. RESULTS: Eight patients (seven with vertical, one with asymmetric horizontal nystagmus) had congenital cone dysfunction. One patient with vertical and another with asymmetric nystagmus had cone-rod dystrophy. One patient with vertical upbeat had congenital stationary night blindness. Two patients (one downbeat, one upbeat nystagmus) had normal electrophysiological, clinical, and brain magnetic resonance imaging findings and were classified as having CIN. One patient with asymmetric nystagmus showed electrophysiological and clinical findings associated with albinism. Horizontal OKN was present in 80% of patients tested, including the three cases with horizontal asymmetric nystagmus. This is atypical in both CIN and SDN, where the OKN is usually absent. CONCLUSIONS: Vertical and asymmetric nystagmus are most commonly associated with serious intracranial pathology and its presence is an indication for neuroimaging studies. However, such nystagmus can occur in children with retinal disease, albinism, and in cases with CIN. These findings stress the importance of non-invasive VEP/ERG testing in all cases of typical and also atypical nystagmus. (+info)
Prospects for treating acquired pendular nystagmus with servo-controlled optics.
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PURPOSE: To determine whether a device featuring electronically controlled motor-driven prisms can reduce oscillopsia and improve acuity in patients with acquired pendular nystagmus (APN). METHODS: A device was developed that senses eye movements and, by the use of motor-driven prisms, oscillates the image of the world in lockstep with the pathologic nystagmus, to negate its deleterious visual effects. Unlike existing optical and surgical treatments for nystagmus, the device negates only the pathologic movements. Voluntary and normal reflex eye movements required for normal vision are unaffected. The benefits of the device were assessed by its impact on acuity in five patients with medication-refractory APN. RESULTS: All patients reported decreases in oscillopsia when the device was in operation. Averaged across patients, the device increased the percentage of time in which retinal image velocity was within +/-4 degrees/sec from 12.8% to 33.3%. Acuities improved in four of five patients, by an average of 0.21 logMAR units. CONCLUSIONS: The symptoms of pendular nystagmus can be treated with a servomechanical device. Further refinements in the device should result in greater improvements in acuity, and a portable, wearable version is feasible using existing technologies. (+info)
Early-onset severe rod-cone dystrophy in young children with RPE65 mutations.
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PURPOSE: To describe the ocular phenotype of patients with RPE65 mutations in infancy and young childhood. METHODS: Four children from three families with severe early-onset visual impairment related to electrophysiologically detectable retinal dystrophy were screened for mutations in the RPE65 gene. Visual function from infancy to the age of 10 years was assessed with age-adapted methods. Clinical examinations and electroretinograms (ERGs) were also performed on the six parents. RESULTS: In all three families, patients were compound heterozygous for mutations of the RPE65 gene (ins144T/IVS1+5G-->A, R91W/Y368H, 1114delA+T457N/IVS1+5G-->A). Visual acuity was measurable in all patients at the age of 6 to 10 years, despite severe visual impairment noted during infancy and congenital nystagmus in three of the four patients. Photophobia was not a feature. Funduscopic changes were discrete, the most prominent finding being increased granularity in the macula and the periphery. Peripheral vision was well preserved, measured by Goldmann perimetry. Rod ERGs were not recordable, whereas cone ERGs were detectable in early childhood. All features taken together suggest a specific form of Leber congenital amaurosis (LCA) distinguishable on clinical grounds. ERGs were normal in five of the six parents. One father had an ERG compatible with congenital stationary night blindness unrelated to his heterozygous state for the RPE65 mutation. CONCLUSIONS: RPE65 mutations on both alleles may be associated with early-onset severe rod-cone dystrophy. Visual functions of the four patients were better than is usually seen in LCA, in particular in cases associated with retGC1 mutations. RPE65 mutations should be suspected in infants who appear to be blind in dim surroundings but react to objects in bright illumination and have nonrecordable rod ERGs and residual cone ERGs. (+info)
The characteristics of dynamic overshoots in square-wave jerks, and in congenital and manifest latent nystagmus.
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Dynamic overshoots are seen after voluntary re-fixation saccades. They are microsaccadic movements which follow primary saccades and have no delay. The purpose of this study was to examine the prevalence and metrics of the dynamic overshoots seen after involuntary saccades. Using infra-red oculography we demonstrate that dynamic overshoots are a common occurrence in physiological square-wave jerks, congenital nystagmus and manifest latent nystagmus and that these overshoots are saccadic in nature and have the same dynamic characteristics as those seen following voluntary saccades. It is therefore likely that they share common neural commands to those dynamic overshoots seen after a volitional saccade. All dynamic overshoots are postulated to be the unwanted consequence of making a saccade and are simulated in a model of fast oculomotor behaviour which is consistent with known experimental results. (+info)
Visual control of postural orientation and equilibrium in congenital nystagmus.
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PURPOSE: To investigate how humans with congenital nystagmus (CN) use visual information to stabilize and orient their bodies in space. METHODS: Center of foot pressure (COP) and head displacements in the lateral plane were recorded using a sway platform and Schottky barrier photodetector, respectively. In experiment 1, a comparison was made of the oscillatory characteristics of body sway with eyes open compared with eyes closed. Experiment 2 studied the postural readjustments made in response to absolute or relative motion (motion parallax) of objects in the visual scene, generated by lateral displacement of background scenery. RESULTS: Experiment 1 revealed that subjects with CN were not able to use visual information to stabilize COP but were able to stabilize the head at frequencies lower than 1 Hz. Experiment 2 showed that in response to the displacement of a visual display, for both absolute motion and motion parallax, subjects with CN reoriented their body in space in a manner similar to control subjects. CONCLUSIONS: The results suggest that despite involuntary eye movements, subjects with CN use orientation cues to control their posture, but not dynamic cues useful to control the rapid oscillations that are particularly important at the level of COP. These findings suggest that in CN, visual control of posture is restricted by low-frequency sampling of the visual scene. (+info)
Deletion in the OA1 gene in a family with congenital X linked nystagmus.
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AIMS: To elucidate the molecular genetic defect of X linked congenital nystagmus associated with macular hypoplasia in three white males of a three generation family with clear features of ocular albinism in only one of them. METHODS: A three generation family with congenital nystagmus following X linked inheritance, and associated with macular hypoplasia was clinically examined (three males and two obligate carriers). Flash VEP was performed to look for albino misrouting. DNA samples were subjected to PCR and subsequent analysis using SSCP for all exons of the OA1 gene. RT-PCR was performed on a mRNA preparation from a naevus from one patient. PCR products presenting divergent banding patterns in SSCP and from the RT-PCR were sequenced directly using cycle sequencing with fluorescent chain termination nucleotides and electrophoresis in a capillary sequencer. RESULTS: The index case (patient 1, IV.1) was diagnosed with X linked OA1 at the age of 3 months because of typical clinical features: congenital nystagmus, iris translucency, macular hypoplasia, fundus hypopigmentation, normal pigmentation of skin and hair, and typical carrier signs of OA1 in his mother and maternal grandmother. Pigmentation of the iris and fundus had increased at the last examination at age 4 years. Albino misrouting was present at this age. In the maternal uncle (III.3, 51 years) who also suffered from congenital nystagmus there was clear macular hypoplasia and stromal focal hypopigmentation of the iris but no iris translucency or fundus hypopigmentation. Patient 3 (II.3, 79 years, maternal uncle of patient III.3) had congenital nystagmus and was highly myopic. The fundus appearance was typical for excessive myopia including macular changes. The iris did not show any translucency. Molecular genetic analysis revealed a novel 14 bp deletion of the OA1 gene at nt816 in exon 6. The mutation abolishes four amino acids (Leu 253-Ile-Ile-Cys) and covers the splice site. Nucleotides 814/815 are used as a new splice donor thus producing a frame shift in codon 252 and a new stop codon at codon 259. CONCLUSIONS: Macular hypoplasia without clinically detectable hypopigmentation as the only sign of X linked OA1 has been reported occasionally in African-American, Japanese, and white patients. The present family shows absent hypopigmentation in two patients of a white family with a deletion in the OA1 gene. We propose a model of OA1 that allows increase of pigmentation with age. We hypothesise that macular hypoplasia in all forms of albinism depends on the extracellular DOPA level during embryogenesis, and that in OA1 postnatal normalisation of the extracellular DOPA level due to delayed distribution and membrane budding/fusion of melanosomes in melanocytes results in increasing pigmentation. (+info)
Clinical and ocular motor analysis of the infantile nystagmus syndrome in the first 6 months of life.
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BACKGROUND/AIMS: The infantile nystagmus syndrome (INS) usually begins in infancy and may or may not be associated with visual sensory system abnormalities. Little is known about its specific waveforms in the first 6 months of life or their relation to the developing visual system. This study identifies the clinical and ocular motility characteristics of the INS and establishes the range of waveforms present in the first 6 months of life. METHODS: 27 infants with involuntary ocular oscillations typical of INS are included in this analysis. They were evaluated both clinically and with motility recordings. Eye movement analysis was performed off line from computer analysis of digitised data. Variables analysed included age, sex, vision, ocular abnormalities, head position, and null zone, neutral zone characteristics, symmetry, conjugacy, waveforms, frequencies, and foveation times. RESULTS: Ages ranged from 3 to 6.5 months (average 4.9 months). 15 patients (56%) had abnormal vision for age, nine (33%) had strabismus, five (19%) had an anomalous head posture, 13 (48%) had oculographic null and neutral positions, nine (33%) had binocular asymmetry, and only two showed consistent dysconjugacy. Average binocular frequency was 3.3 Hz, monocular frequency 6.6 Hz. Average foveation periods were longer and more "jerk" wave forms were observed in those patients with normal vision. CONCLUSIONS: Common clinical characteristics and eye movement waveforms of INS begin in the first few months of infancy and waveform analysis at this time may help with both diagnosis and visual status. (+info)