RESUMO
Genes causing nonsyndromic autosomal recessive deafness (DFNB12) and deafness associated with retinitis pigmentosa and vestibular dysfunction (USH1D) were previously mapped to overlapping regions of chromosome 10q21-q22. Seven highly consanguineous families segregating nonsyndromic autosomal recessive deafness were analyzed to refine the DFNB12 locus. In a single family, a critical region was defined between D10S1694 and D10S1737, approximately 0.55 cM apart. Eighteen candidate genes in the region were sequenced. Mutations in a novel cadherin-like gene, CDH23, were found both in families with DFNB12 and in families with USH1D. Six missense mutations were found in five families with DFNB12, and two nonsense and two frameshift mutations were found in four families with USH1D. A northern blot analysis of CDH23 showed a 9.5-kb transcript expressed primarily in the retina. CDH23 is also expressed in the cochlea, as is demonstrated by polymerase chain reaction amplification from cochlear cDNA.
Assuntos
Alelos , Caderinas/genética , Surdez/genética , Genes Recessivos/genética , Perda Auditiva Neurossensorial/genética , Mutação/genética , Retinose Pigmentar/genética , Sequência de Aminoácidos , Sequência de Bases , Proteínas Relacionadas a Caderinas , Mapeamento Cromossômico , Consanguinidade , Análise Mutacional de DNA , Primers do DNA , Éxons/genética , Feminino , Frequência do Gene/genética , Humanos , Íntrons/genética , Escore Lod , Masculino , Linhagem , RNA Mensageiro/análise , RNA Mensageiro/genética , SíndromeRESUMO
During development, visual photoreceptors, bipolar cells and other neurons establish connections within the retina enabling the eye to process visual images over approximately 7 log units of illumination. Within the retina, cells that respond to light increment and light decrement are separated into ON- and OFF-pathways. Hereditary diseases are known to disturb these retinal pathways, causing either progressive degeneration or stationary deficits. Congenital stationary night blindness (CSNB) is a group of stable retinal disorders that are characterized by abnormal night vision. Genetic subtypes of CSNB have been defined and different disease actions have been postulated. The molecular bases have been elucidated in several subtypes, providing a better understanding of the disease mechanisms and developmental retinal neurobiology. Here we have studied 22 families with 'complete' X-linked CSNB (CSNB1; MIM 310500; ref. 4) in which affected males have night blindness, some photopic vision loss and a defect of the ON-pathway. We have found 14 different mutations, including 1 founder mutation in 7 families from the United States, in a novel candidate gene, NYX. NYX, which encodes a glycosylphosphatidyl (GPI)-anchored protein called nyctalopin, is a new and unique member of the small leucine-rich proteoglycan (SLRP) family. The role of other SLRP proteins suggests that mutant nyctalopin disrupts developing retinal interconnections involving the ON-bipolar cells, leading to the visual losses seen in patients with complete CSNB.
Assuntos
Proteínas do Olho/genética , Genes , Interneurônios/patologia , Cegueira Noturna/genética , Proteoglicanas/genética , Cromossomo X/genética , Adulto , Motivos de Aminoácidos , Sequência de Aminoácidos , Análise Mutacional de DNA , DNA Complementar/genética , Etiquetas de Sequências Expressas , Proteínas do Olho/química , Proteínas do Olho/fisiologia , Perfilação da Expressão Gênica , Glicosilfosfatidilinositóis/metabolismo , Humanos , Interneurônios/metabolismo , Rim/metabolismo , Leucina/análise , Masculino , Dados de Sequência Molecular , Cegueira Noturna/classificação , Especificidade de Órgãos , Linhagem , Proteoglicanas/química , Proteoglicanas/deficiência , Proteoglicanas/fisiologia , Sequências Repetitivas de Aminoácidos , Retina/patologia , Células Ganglionares da Retina/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Transmissão Sináptica/fisiologia , Visão Ocular/fisiologiaRESUMO
PURPOSE: With the use of the pattern reversal visual evoked potential and the motor reaction time, we sought to differentiate anisometropic amblyopia from strabismic amblyopia on the basis of the visual transmission time. METHODS: Pattern reversal visual evoked potentials and motor reaction times were obtained in nine normal subjects, eight anisometropic and seven strabismic amblyopes. RESULTS: Our results show that while the peak time of the pattern visual evoked potential in anisometropic amblyopia and strabismic amblyopia was significantly delayed, it could not distinguish the two types of amblyopia. In contrast, a significantly longer interocular increment in strabismics compared to anisometropes was found with the reaction time, but not with the pattern visual evoked potential. CONCLUSION: Our findings thus show that it is possible to distinguish strabismic from anisometropic amblyopes using interocular differences in reaction time measurements. Our results bring support to the contention that the two types of amblyopia represent different neural abnormalities.
Assuntos
Ambliopia/diagnóstico , Anisometropia/diagnóstico , Potenciais Evocados Visuais , Desempenho Psicomotor , Tempo de Reação , Estrabismo/diagnóstico , Adulto , Ambliopia/fisiopatologia , Anisometropia/fisiopatologia , Diagnóstico Diferencial , Potenciais Evocados Visuais/fisiologia , Humanos , Desempenho Psicomotor/fisiologia , Estrabismo/fisiopatologia , Acuidade VisualRESUMO
We report on a family where four of the eleven children presented with reduced visual acuities, a red-green deficit at the Farnsworth-Munsel FM 100-hue test, normal appearing fundi and unexpected electroretinographic findings. Light- (photopic) and dark- (scotopic) adapted electroretinograms (ERG) and oscillatory potentials (OPs) were obtained following an accepted standard protocol. The b-wave of their photopic ERG was significantly more attenuated than the a-wave due to the specific abolition of OP4, while the amplitudes of OP2 and OP3 were within the normal range, giving to the b-wave a truncated appearance reminiscent of that seen in congenital stationary night blindness (CSNB) with myopia. Interestingly in the latter condition, which is believed to result from an ON-retinal pathway anomaly, it is OP2 and OP3 which are specifically abolished while OP4 is of normal amplitude thus resulting in an OP response pattern which complements that seen with our patients. Also of interest is the fact that, in our patients, the amplitude of the dark-adapted OP2 was, on average, 240% larger than that measured in light-adaptation while, in normal, a non-significant 14% increase is noted; a finding which is in keeping with other studies reporting supernormal scotopic ERGs in some forms of cone dystrophies. Based on the photopic OP response pattern, our patients represent the electrophysiological complement of patients affected with CSNB. Interestingly their symptoms are also complementary, a finding which could support a functional discrimination between the photopic OPs.
Assuntos
Células Fotorreceptoras Retinianas Cones/fisiopatologia , Degeneração Retiniana/fisiopatologia , Células Fotorreceptoras Retinianas Bastonetes/fisiopatologia , Adolescente , Adulto , Criança , Pré-Escolar , Adaptação à Escuridão , Eletrorretinografia , Feminino , Angiofluoresceinografia , Fundo de Olho , Humanos , Lactente , Masculino , Miopia/congênito , Miopia/genética , Miopia/fisiopatologia , Cegueira Noturna/congênito , Cegueira Noturna/genética , Cegueira Noturna/fisiopatologia , Linhagem , Estimulação Luminosa , Células Fotorreceptoras Retinianas Cones/patologia , Degeneração Retiniana/diagnóstico , Degeneração Retiniana/genética , Células Fotorreceptoras Retinianas Bastonetes/patologiaRESUMO
We report on an 8-year-old boy with clinical manifestations suggestive of a new arthrogryposis syndrome. These included characteristic craniofacial abnormalities, cleft palate, arthrogryposis multiplex congenita, pulmonary hypoplasia, cryptorchidism, and unusual ophthalmological findings. There was no intrauterine growth retardation or decreased fetal movements. Despite the poor prognosis expected in early life, the patient presented with normal mental capability on follow-up. Family data showed that a maternal first cousin of the mother (mother's brother's son) had similar findings and died in infancy. Differential diagnosis included Pena-Shokeir syndrome or phenotype, Gordon syndrome, Marden-Walker syndrome, and the syndrome of arthrogryposis with ophthalmoplegia and retinopathy. The possibility of autosomal dominant inheritance with reduced penetrance is suggested for this apparently new syndrome.
Assuntos
Anormalidades Múltiplas/genética , Anormalidades Craniofaciais/genética , Anormalidades do Olho/genética , Anormalidades Múltiplas/classificação , Anormalidades Múltiplas/diagnóstico por imagem , Criança , Anormalidades Craniofaciais/classificação , Anormalidades Craniofaciais/diagnóstico por imagem , Diagnóstico Diferencial , Anormalidades do Olho/classificação , Anormalidades do Olho/diagnóstico por imagem , Feminino , Humanos , Inteligência , Masculino , Radiografia , SíndromeRESUMO
Progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy syndrome is a recently described rare disorder of infantile regression, intractable seizures, and cerebellar atrophy that occurs almost exclusively in the Finnish population. We report the first North American child with this condition.
Assuntos
Edema Encefálico/genética , Cerebelo/patologia , Atrofia Óptica/genética , Espasmos Infantis/genética , Atrofia , Pré-Escolar , Eletroencefalografia , Potenciais Evocados/fisiologia , Feminino , Seguimentos , Humanos , Lactente , Imageamento por Ressonância Magnética , Exame Neurológico , SíndromeRESUMO
The Usher syndromes (USH) are a group of autosomal recessive diseases characterized by progressive pigmentary retinopathy and sensorineural hearing loss. Five USH genes have been mapped and at least one additional gene is known to exist. By homozygosity mapping in a consanguineous family, a sixth USH gene has been localized. Clinical findings in the four affected children are consistent with established diagnostic criteria for Ush1. Linkage to known USH loci was excluded, and using two genomic DNA pools, one from the affected children and the other from the parents, 161 polymorphic markers evenly spaced across the autosomal human genome were screened. The location of the Ush1D gene was defined by the only region showing homozygosity by descent in the affected siblings, a 15 cM interval on chromosome 10q bounded by D10S529 and D10S573.
Assuntos
Cromossomos Humanos Par 10 , Perda Auditiva Neurossensorial/genética , Retinose Pigmentar/genética , Mapeamento Cromossômico , Ligação Genética , Humanos , SíndromeRESUMO
PURPOSE: The purpose of this study is to determine the incidence of secondary hemorrhage after traumatic hyphema in children and to evaluate the efficacy of epsilon aminocaproic acid in reducing this incidence. METHODS: In a prospective, randomized, double-blind study performed between November 1987 and February 1994, 94 children admitted for traumatic hyphema were assigned to receive either aminocaproic acid (n = 48) (100 mg/kg every 4 hours; maximum, 30 g daily) or placebo (n = 46) for 5 days. Patients who had ingested aspirin in the week preceding admission were excluded from the study. RESULTS: Mean age of the patients was 9.4 years. Black patients comprised 4% of the study population. Secondary hemorrhage occurred in only three patients (3.2%), two from the placebo group and one from the aminocaproic acid group, none of whom had any complications. The duration of hospital stay and the clot resorption times were increased significantly in the aminocaproic acid group (P < 0.001). CONCLUSIONS: The authors report a very low incidence of secondary hemorrhage compared with most previous studies. This difference is likely related to the small proportion of black patients in our study and to the exclusion of patients having ingested aspirin, two factors that seem to be associated with higher rates of rebleeding. The efficacy of aminocaproic acid could not be determined due to the low incidence of hemorrhage. The results of this study, however, suggest that the incidence of secondary hemorrhage in white patients without prior ingestion of aspirin is insufficient to justify routine use of aminocaproic acid in managing traumatic hyphema. Rather, an individualized decision based on the risk factors of each patient would seem more appropriate to avoid a slower clot resorption time and possible side effects of this medication.
Assuntos
Ácido Aminocaproico/uso terapêutico , Antifibrinolíticos/uso terapêutico , Traumatismos Oculares/tratamento farmacológico , Hifema/tratamento farmacológico , Ferimentos não Penetrantes/tratamento farmacológico , Administração Oral , Ácido Aminocaproico/administração & dosagem , Antifibrinolíticos/administração & dosagem , Criança , Método Duplo-Cego , Traumatismos Oculares/etiologia , Feminino , Seguimentos , Humanos , Hifema/etiologia , Pressão Intraocular , Masculino , Estudos Prospectivos , Recidiva , Resultado do Tratamento , Acuidade Visual , Ferimentos não Penetrantes/etiologiaAssuntos
Agenesia do Corpo Caloso , Doenças da Coroide/patologia , Nervo Óptico/anormalidades , Doenças Retinianas/patologia , Espasmos Infantis/patologia , Coloboma/patologia , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Evolução Fatal , Feminino , Humanos , Recém-Nascido , Microftalmia/diagnóstico por imagem , Microftalmia/patologia , Nervo Óptico/patologia , Epitélio Pigmentado Ocular/patologia , Síndrome , Tomografia Computadorizada por Raios XRESUMO
Usher syndrome is a heterogeneous group of disorders of autosomal recessive inheritance characterized by retinitis pigmentosa and congenital sensorineural hearing loss. Two types are accepted clinically: type I is associated with profound congenital deafness with progressive pigmentary retinopathy and total loss of vestibular function. Type II is a milder form, with moderate-to-profound hearing loss and a milder form of retinitis pigmentosa. Vestibular function is preserved. A total of five loci have been identified as accounting for the two distinct phenotypic presentations. We describe a consanguineous family of Pakistani origin whose four children all are affected with Usher syndrome type I. DNA analysis showed non-linkage to any of the loci already identified as tightly linked to the Usher syndrome type I.
Assuntos
Consanguinidade , Perda Auditiva Neurossensorial/complicações , Retinose Pigmentar/complicações , Canadá/etnologia , Criança , Aberrações Cromossômicas , Transtornos Cromossômicos , Feminino , Perda Auditiva Neurossensorial/congênito , Perda Auditiva Neurossensorial/genética , Humanos , Masculino , Paquistão , Pais , Retinose Pigmentar/genética , SíndromeRESUMO
The contribution of each monocular pathway to the timing of the binocular pattern visual evoked potential was assessed in situations where a significant interocular timing discrepancy was observed. Monocular and binocular pattern visual evoked potentials to 0.5 degree checks were recorded from normal subjects, normal subjects in whom one eye was blurred, patients with monocular amblyopia, and patients with resolved unilateral optic neuritis. Normal subjects showed facilitation, while suppression was evidenced in subjects with monocular blurring. In patients with amblyopia, the affected pathway had no effect on binocular pattern visual evoked potential latency, suggesting that the amblyopic eye was suppressed. In contrast, all patients with optic neuritis showed binocular averaging. Our results show that different forms of binocular interaction are evidenced in normal subjects, in amblyopia and in optic neuritis, and suggest that a comparative analysis of monocular and binocular pattern visual evoked potential peak times brings valuable information to the clinical evaluation that could be used to distinguish disease processes further.
Assuntos
Ambliopia/fisiopatologia , Potenciais Evocados Visuais/fisiologia , Neurite Óptica/fisiopatologia , Visão Binocular/fisiologia , Visão Monocular/fisiologia , Adolescente , Adulto , Criança , Humanos , Reconhecimento Visual de Modelos , Acuidade VisualRESUMO
Experimentally induced strabismus in visually immature cats leads to abnormal development of the posterior corpus callosum. This, in turn, should lead to abnormal interhemispheric integration of unilaterally presented visual information. To test whether strabismus produces deficits in the human commissural visual system, the interhemispheric transmission time (ITT) was compared in strabismic and normal subjects. Simple unimanual reaction times (RT) were tested in 30 subjects in response to a lateralized target presented monocularly at 4 degrees and 35 degrees nasally and temporally from the fovea along the horizontal meridian. This method was also used to examine the effect of strabismus on the central and peripheral portions of each hemiretina. The results showed that in strabismic subjects with or without amblyopia, the ITT did not differ significantly from normals at both eccentricities. In non-amblyopic strabismic patients, RTs in the central and peripheral portions of hemiretina were comparable to normals. However, a reduced speed of response was found in the central visual field (4 degrees) in the amblyopic eye. Our results suggest that the ITT is normal in strabismic subjects and that the longer RTs in the central portion of the nasal and temporal hemiretina of the amblyopic eye may be associated with the severe amblyopic condition.
Assuntos
Dominância Cerebral/fisiologia , Tempo de Reação/fisiologia , Retina/fisiologia , Estrabismo/fisiopatologia , Transmissão Sináptica/fisiologia , Campos Visuais/fisiologia , Adolescente , Adulto , Ambliopia/fisiopatologia , Atenção/fisiologia , Mapeamento Encefálico , Feminino , Humanos , Masculino , Visão Monocular/fisiologia , Vias Visuais/fisiologiaAssuntos
Neoplasias Orbitárias/congênito , Neoplasias Orbitárias/patologia , Teratoma/congênito , Teratoma/patologia , Proteínas do Citoesqueleto/metabolismo , Exoftalmia/diagnóstico por imagem , Feminino , Humanos , Técnicas Imunoenzimáticas , Recém-Nascido , Órbita/diagnóstico por imagem , Neoplasias Orbitárias/metabolismo , Teratoma/metabolismo , Tomografia Computadorizada por Raios X , alfa-Fetoproteínas/metabolismoRESUMO
It has recently been suggested that aberrant misrouting of retino-geniculate-cortical (RGC) projections, a finding previously noted only in albinism, may be an additional feature of the Prader-Willi syndrome. To determine the prevalence of ocular abnormalities in patients with the syndrome and to look for evidence of misrouted RGC projections by means of testing of the pattern-onset visual evoked potential (VEP) response, we examined 12 patients with Prader-Willi syndrome, 8 albino subjects and 5 healthy control subjects. Ocular findings in the first group included telecanthus (in five subjects), strabismus, nystagmus, foveal hypoplasia, visual field defects and cataract. However, the VEP asymmetry typically seen in albinism was not noted in any of the patients with Prader-Willi syndrome. Our findings do not support previous claims of abnormal optic nerve fibre decussation in Prader-Willi syndrome.
Assuntos
Potenciais Evocados Visuais , Doenças do Nervo Óptico/fisiopatologia , Síndrome de Prader-Willi/fisiopatologia , Adolescente , Adulto , Albinismo Ocular/fisiopatologia , Albinismo Oculocutâneo/fisiopatologia , Criança , Pré-Escolar , Oftalmopatias/fisiopatologia , Feminino , Humanos , Masculino , Acuidade VisualRESUMO
We describe a family with familial adenomatous polyposis (FAP) and congenital hypertrophy of the retinal pigment epithelium (RPE). Three of five members with FAP showed flat, well-demarcated, round to oval pigmented patches of congenital hypertrophy of the RPE. We stress the importance of congenital hypertrophy of the RPE as a clinical marker in identifying patients with FAP since they are at risk for cancer.
Assuntos
Polipose Adenomatosa do Colo/complicações , Epitélio Pigmentado Ocular/fisiopatologia , Polipose Adenomatosa do Colo/genética , Adulto , Feminino , Angiofluoresceinografia , Fundo de Olho , Ligação Genética , Humanos , Hipertrofia/complicações , Hipertrofia/congênito , Hipertrofia/genética , Masculino , Linhagem , Fatores de RiscoRESUMO
We studied a family with Leber's congenital amaurosis and Duchenne's muscular dystrophy. One son, the proband, was noted to be blind from shortly after birth and had absent pupillary reflexes, attenuation of retinal blood vessels and pigmentary changes of the retina. He manifested Duchenne's muscular dystrophy at 6 years of age and died of its complication--severe respiratory failure--at 21 years of age. His older brother also was blind since birth, with absent pupillary light reflexes and an extinguished electroretinogram in both eyes. The proband's younger brother with Duchenne's muscular dystrophy died following respiratory failure. Their oldest brother was apparently unaffected. Their mother and sister were proven carriers of Duchenne's muscular dystrophy and a maternal uncle and great-uncle also died from this condition. The parents were consanguineous, third generation cousins.
Assuntos
Neuropatia Hereditária Motora e Sensorial/complicações , Distrofias Musculares/complicações , Atrofias Ópticas Hereditárias/complicações , Adolescente , Adulto , Criança , DNA/análise , Sondas de DNA , Estudos de Avaliação como Assunto , Feminino , Triagem de Portadores Genéticos , Humanos , Masculino , Distrofias Musculares/genética , Distrofias Musculares/patologia , Mutação , Atrofias Ópticas Hereditárias/genética , Atrofias Ópticas Hereditárias/patologia , Linhagem , Polimorfismo de Fragmento de RestriçãoRESUMO
The increases in tension at the masseter and adductor pollicis muscles following succinylcholine, 1 mg.kg-1, during halothane anaesthesia were measured in eight children, 3-10 yr, with strabismus. The results were compared with those obtained in a control group of general surgical patients. Supramaximal train-of-four (TOF) stimulation was applied to the ulnar nerve and the nerve to the masseter simultaneously. Jaw closure was measured by a force transducer system. In all patients, succinylcholine caused an increase in resting tone at the jaw and at the thumb. In the strabismus group, the magnitude of this increase was 55.7 +/- 23.2 g, mean +/- SD, at the jaw and 11.3 +/- 5.6 g at the thumb. This was not significantly different from the values obtained in controls, 45.3 +/- 33.4 g and 7.9 +/- 4.2 g, respectively. The duration of the phenomenon was 1-2 min in both muscles studied, and was not statistically different in the strabismus group. Time to complete neuromuscular blockade was significantly faster at the masseter, 31 +/- 6 sec--control groups; 39 +/- 11 sec--strabismus group, than at adductor pollicis, 61 +/- 34 sec--control groups; 75 +/- 28 sec--strabismus group (P less than 0.05 and 0.013 respectively). It is concluded that succinylcholine causes similar increases in jaw tension and comparable degrees of neuromuscular blockade in patients undergoing strabismus surgery as in other children.
Assuntos
Anestesia por Inalação , Músculo Masseter/efeitos dos fármacos , Músculos da Mastigação/efeitos dos fármacos , Estrabismo/cirurgia , Succinilcolina/farmacologia , Criança , Pré-Escolar , Estimulação Elétrica , Feminino , Humanos , Masculino , Músculo Masseter/inervação , Músculo Masseter/fisiopatologia , Junção Neuromuscular/efeitos dos fármacos , Junção Neuromuscular/fisiopatologia , Estrabismo/fisiopatologiaRESUMO
The increases in tension at the masseter and adductor pollicis muscles following succinylcholine, 1 mg · kg-1, during halothane anaesthesia were measured in eight children, 3-10 yr, with strabismus. The results were compared with those obtained in a control group of general surgical patients. Supramaximal train-of-four (TOF) stimulation was applied to the ulnar nerve and the nerve to the masseter simultaneously. Jaw closure was measured by a force transducer system. In all patients, succinylcholine caused an increase in resting tone at the jaw and at the thumb. In the strabismus group, the magnitude of this increase was 55.7 ±23.2 g, mean ±SD, at the jaw and 11.3 ±5.6 g at the thumb. This was not significantly different from the values obtained in controls, 45.3 ±33.4 g and 7.9 ±4.2 g, respectively. The duration of the phenomenon was 1-2 min in both muscles studied, and was not statistically different in the strabismus group. Time to complete neuromuscular blockade was significantly faster at the masseter, 31 ±6 sec -control groups; 39 ±11 sec -strabismus group, than at adductor pollicis, 61 ±34 sec -control groups; 75 ±28 sec -strabismus group (P < 0.05 and 0.013 respectively). It is concluded that succinylcholine causes similar increases in jaw tension and comparable degrees of neuromuscular blockade in patients undergoing strabismus surgery as in other children.
RESUMO
Acute administration of diphenylhydantoin (DPH) in rabbits produces a significant increase in the amplitude of the a-wave. A marked increase in the amplitude of the b-wave is also noted but the time course is slower than that for the a-wave. While in controls the oscillatory potential (OP) recordings essentially consist of three major types, recordings taken after DPH injection consist of one major OP (OP2), which appears to be a result of the fusion of the original OP2 with another OP produced by the DPH injection. A similar blend of OPs was also seen in ERGs recorded from three human subjects on DPH therapy.