Asunto(s)
ADN Helicasas , Enzimas Multifuncionales , ARN Helicasas , Humanos , Enzimas Multifuncionales/genética , ARN Helicasas/genética , Masculino , ADN Helicasas/genética , Femenino , Apraxias/genética , Apraxias/fisiopatología , Apraxias/congénito , Síndrome de Cogan/genética , Adulto , Linaje , Ataxias Espinocerebelosas/genética , Ataxias Espinocerebelosas/congénito , Ataxias Espinocerebelosas/patología , MutaciónRESUMEN
We describe here a 73-year-old patient presenting with atypical MSA-P-like phenotype carrying a monoallelic p. W279X mutation in the APTX gene, which causes ataxia with oculomotor apraxia type 1 (AOA1) when in homozygous state. We hypothesize that rare monoallelic APTX variants could modulate MSA risk and phenotype.
Asunto(s)
Atrofia de Múltiples Sistemas , Fenotipo , Anciano , Humanos , Masculino , Apraxias/genética , Apraxias/congénito , Síndrome de Cogan/genética , Proteínas de Unión al ADN/genética , Heterocigoto , Atrofia de Múltiples Sistemas/genética , MutaciónRESUMEN
Cogan's syndrome is a rare autoimmune inflammatory disease, characterized by interstitial keratitis and audio-vestibular signs. The syndrome was first described in 1945 by David G. Cogan. Then, it was only in 1980 when Haynes et al. proposed diagnostic criteria for patients with other symptoms and was qualified as atypical form of Cogan's syndrome. Herein, we report a case of a 28-year-old woman with atypical Cogan's syndrome. The patient was treated with corticosteroids and received a cochlear implant.
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Apraxias/congénito , Enfermedades Autoinmunes , Implantes Cocleares , Síndrome de Cogan , Queratitis , Femenino , Humanos , Adulto , Síndrome de Cogan/complicaciones , Síndrome de Cogan/diagnóstico , Queratitis/diagnóstico , SíndromeAsunto(s)
Apraxias/congénito , Síndrome de Cogan , Humanos , Adulto Joven , Movimientos Sacádicos , CogniciónRESUMEN
Behçet's syndrome and Cogan's syndrome constitute the group of variable vessel vasculitides in the Chapel-Hill Nomenclature. They involve arteries and veins of all sizes. As reflected in the name "syndrome", both diseases can manifest with different individual symptoms. Both formally are rare diseases, but the Cogan syndrome is much rarer than Behçet`s. For the latter, there are diagnosis and classification criteria as well as European (EULAR, European Alliance of Associations for Rheumatology) treatment recommendations. The symptomatology, diagnostic measures and treatment as well as some considerations about pathogenesis will be discussed in this article.
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Apraxias/congénito , Síndrome de Behçet , Síndrome de Cogan , Vasculitis , Humanos , Síndrome de Cogan/diagnóstico , Síndrome de Behçet/diagnóstico , Vasculitis/diagnóstico , Diagnóstico DiferencialRESUMEN
BACKGROUND: Cogan´s syndrome is a rare, presumed autoimmune vasculitis of various vessels characterized by interstitial keratitis and vestibular impairment accompanied by sensorineural hearing loss. Due to the rarity of Cogan´s syndrome in children, therapeutic decision making may be challenging. Therefore, a literature search was performed to collect all published paediatric Cogan´s syndrome cases with their clinical characteristics, disease course, treatment modalities used and their outcome. The cohort was supplemented with our own patient. MAIN TEXT: Altogether, 55 paediatric Cogan´s syndrome patients aged median 12 years have been reported so far. These were identified in PubMed with the keywords "Cogan´s syndrome" and "children" or "childhood". All patients suffered from inflammatory ocular and vestibulo-auditory symptoms. In addition, 32/55 (58%) manifested systemic symptoms with musculoskeletal involvement being the most common with a prevalence of 45%, followed by neurological and skin manifestations. Aortitis was detected in 9/55 (16%). Regarding prognosis, remission in ocular symptoms was attained in 69%, whereas only 32% achieved a significant improvement in auditory function. Mortality was 2/55. Our patient was an 8 year old girl who presented with bilateral uveitis and a history of long standing hearing deficit. She also complained of intermittent vertigo, subfebrile temperatures, abdominal pain with diarrhoea, fatigue and recurrent epistaxis. The diagnosis was supported by bilateral labyrinthitis seen on contrast-enhanced magnetic resonance imaging. Treatment with topical and systemic steroids was started immediately. As the effect on auditory function was only transient, infliximab was added early in the disease course. This led to a remission of ocular and systemic symptoms and a normalization of hearing in the right ear. Her left ear remained deaf and the girl is currently evaluated for a unilateral cochlear implantation. CONCLUSIONS: This study presents an analysis of the largest cohort of paediatric Cogan´s syndrome patients. Based on the collected data, the first practical guide to a diagnostic work-up and treatment in children with Cogan´s syndrome is provided.
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Apraxias , Síndrome de Cogan , Pérdida Auditiva Sensorineural , Queratitis , Niño , Femenino , Humanos , Síndrome de Cogan/complicaciones , Síndrome de Cogan/diagnóstico , Síndrome de Cogan/terapia , Progresión de la Enfermedad , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/etiología , Pérdida Auditiva Sensorineural/terapia , Queratitis/diagnóstico , Queratitis/terapia , Queratitis/complicaciones , Pronóstico , Apraxias/congénitoRESUMEN
BACKGROUND: Cogan syndrome is a rare inflammatory condition that mainly affects adults and is characterised by inflammation of various ocular structures and by audiovestibular symptoms such as hearing loss and vertigo. CASE DESCRIPTION: A 63-year old woman recently diagnosed with an anterior uveitis presented at A&E with vertigo, nausea, vomiting, tinnitus and headache, and she developed bilateral sudden deafness within days. Blood testing revealed elevated inflammatory parameters, without signs of infection. Additional laboratory and imaging tests showed no abnormalities. We finally diagnosed her with Cogan syndrome. Our patient started oral prednisolon and methotrexate and she gradually improved. CONCLUSION: Cogan syndrome is a rare inflammatory condition that warrants a multidisciplinary approach by an ophthalmologist, neurologist, ENT-physician, and rheumatologist / immunologist for swift diagnosis and treatment with immunosuppressive medication. A timely recognition of the syndrome at first presentation and with new flares improves the chances of full or partial recovery.
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Síndrome de Cogan , Adulto , Apraxias/congénito , Síndrome de Cogan/complicaciones , Síndrome de Cogan/diagnóstico , Síndrome de Cogan/tratamiento farmacológico , Femenino , Humanos , Inflamación , Persona de Mediana Edad , Prednisolona , Vértigo/diagnóstico , Vértigo/etiologíaAsunto(s)
Ataxia Cerebelosa , Síndrome de Cogan , Miopía , Apraxias/congénito , Humanos , Mutación , Miopía/genética , LinajeRESUMEN
BACKGROUND: Ataxia with oculomotor apraxia (AOA) is characterized by early-onset cerebellar ataxia associated with oculomotor apraxia. AOA1, AOA2, AOA3, and AOA4 subtypes may present pathogenic variants in APTX, SETX, PIK3R5, and PNKP genes, respectively. Mutations in XRCC1 have been found to cause autosomal recessive spinocerebellar ataxia-26 (SCAR26) now considered AOA5. OBJECTIVES: To examine a cohort of Brazilians with autosomal recessive cerebellar ataxia plus oculomotor apraxia and determine the frequencies of AOA subtypes through genetic investigation. METHODS: We evaluated clinical, biomarkers, electrophysiological, and radiological findings of 52 patients with AOA phenotype and performed a genetic panel including APTX, SETX, PIK3R5, PNKP, and XRCC1. RESULTS: We found pathogenic variants in SETX (15 patients), PNKP (12), and APTX (5). No mutations in PIK3R5 or XRCC1 were identified. CONCLUSIONS: AOA2 and AOA4 were the most common forms of AOA in Brazil. Mutations in PIK3R5 and XRCC1 were not part of this genetic spectrum. © 2022 International Parkinson and Movement Disorder Society.
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Apraxias , Ataxia Cerebelosa , Apraxias/congénito , Apraxias/genética , Ataxia/genética , Brasil , Ataxia Cerebelosa/complicaciones , Ataxia Cerebelosa/genética , Síndrome de Cogan , ADN Helicasas/genética , Enzimas Reparadoras del ADN/genética , Humanos , Enzimas Multifuncionales/genética , Mutación/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , ARN Helicasas/genética , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos X/genéticaRESUMEN
BACKGROUND Cogan syndrome is a rare autoimmune disorder associated most frequently with ocular, vestibular, and auditory involvement from presumed small vessel vasculitis. Cogan syndrome, in a significant proportion of patients, can progress to systemic symptoms, including gastrointestinal, neurologic, and musculoskeletal manifestations. Large-vessel involvement has also been described in some cases (eg, aortitis), but acute limb ischemia in the setting of this illness has been infrequently reported. CASE REPORT We present a rare case of Cogan syndrome complicated by acute vascular ischemia of the left upper extremity. A 50-year-old man presented with symptoms of severe acute pain and weakness of the left arm. The patient endorsed a diagnosis of Cogan syndrome 4 years prior in the setting of unilateral left-sided hearing loss and bilateral uveitis. A physical examination revealed pallor of the left forearm and pulselessness at the wrist. Computed tomography angiography was suggestive of vasculitis and concerns for embolic occlusion of several arterial structures of the left upper limb. After consultation with various specialists, the patient was treated with high-dose steroids, anticoagulants, and topical nitroglycerin and experienced significant clinical improvement. CONCLUSIONS Treatment of Cogan syndrome with severe systemic manifestations depends on the organ involvement and degree of extension. Our patient's presentation serves as an impressive example of systemic vasculitis with subsequent acute ischemia in the setting of this rare autoimmune disorder. In such a case, given the potential for life- or limb-threatening systemic vascular catastrophes, emergent interventions (including imaging, anticoagulation, and specialist involvement) are required to prevent untoward outcomes.
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Enfermedades Autoinmunes , Síndrome de Cogan , Enfermedades Vasculares Periféricas , Vasculitis , Apraxias/congénito , Enfermedades Autoinmunes/diagnóstico , Síndrome de Cogan/complicaciones , Síndrome de Cogan/diagnóstico , Humanos , Isquemia/complicaciones , Isquemia/etiología , Masculino , Persona de Mediana Edad , Vasculitis/complicacionesRESUMEN
Cogan I syndrome is a rare disease consisting of vestibulocochlear symptoms and non-syphilitic interstitial keratitis. Although this disease was first described in 1945, its pathogenesis is still unknown. An autoimmune vasculitis etiology is currently discussed. Atypical manifestations are characterized by delayed ocular symptoms or variability of inflammatory eye symptoms. Physical examination often reveals bilateral sensorineural hearing loss. Intratympanic corticosteroid application can be successful.
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Síndrome de Cogan , Pérdida Auditiva Sensorineural , Pérdida Auditiva Súbita , Queratitis , Apraxias/congénito , Síndrome de Cogan/complicaciones , Síndrome de Cogan/diagnóstico , Diagnóstico Diferencial , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/etiología , Pérdida Auditiva Súbita/diagnóstico , Pérdida Auditiva Súbita/etiología , Humanos , Queratitis/diagnóstico , SíndromeRESUMEN
PURPOSE: To systematically compare idiopathic and non-idiopathic ocular motor apraxia (OMA) in children. METHODS: A retrospective chart review was conducted of all children (< 18 years) diagnosed as having OMA from 2010 to 2020. Demographics, clinical characteristics, and oculomotor outcomes were compared for children with idiopathic and non-idiopathic OMA. RESULTS: Thirty-seven children were included, 17 (46%) with idiopathic OMA and 20 (54%) with non-idiopathic OMA. Among patients with non-idiopathic OMA, Joubert syndrome was the most frequent underlying diagnosis (30%). Strabismus (45% vs 12%, P = .04), nystagmus (30% vs 0%, P = .02), and vertical saccade involvement (25% vs 0%, P = .049) were significantly more common in non-idiopathic than idiopathic OMA, respectively. Neuroimaging abnormalities (90% vs 18%, P < .0001) and developmental delays (100% vs 59%, P = .002) were also more frequent in non-idiopathic than idiopathic OMA, respectively. Endocrine disorders (most commonly growth hormone deficiency) were diagnosed in 12% and 20% of children with idiopathic and non-idiopathic OMA, respectively (P = .67). On survival curve analysis, improvement in OMA occurred faster and more frequently in children with idiopathic than non-idiopathic OMA (median time to improvement 56 vs 139 months, respectively, P = .034). CONCLUSIONS: Non-idiopathic OMA is associated with a higher rate of vertical saccade involvement, nystagmus, and developmental delays. These findings should prompt neuroimaging in children with OMA. Additionally, endocrine disorders may be more frequent in children with OMA than the general pediatric population. [J Pediatr Ophthalmol Strabismus. 2022;59(5):326-331.].
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Síndrome de Cogan , Nistagmo Patológico , Trastornos de la Motilidad Ocular , Apraxias/congénito , Niño , Síndrome de Cogan/complicaciones , Síndrome de Cogan/diagnóstico , Hormona del Crecimiento , Humanos , Trastornos de la Motilidad Ocular/diagnóstico , Estudios RetrospectivosRESUMEN
Cogan's syndrome (CS) is a rare autoimmune vasculitis of unknown aetiology characterised by non-syphilitic interstitial keratitis, audiovestibular symptoms, sometimes systemic symptoms, and multi-organ involvement. Atypical CS has other ocular features, such as scleritis, episcelritis, retinitis, and optic neuritis. Diagnosis of CS is purely clinical without a confirmatory test. Hereby, we report a case of atypical CS presenting with features of encephalitis who was treated successfully with intravenous pulse methylprednisolone with cyclophosphamide. It is important to consider CS in the differential diagnosis of encephalitis with ocular and vestibular symptoms in young patients, as high morbidity and mortality rates are effectively lowered by early immunosuppressive treatment.
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Síndrome de Cogan , Encefalitis , Apraxias/congénito , Síndrome de Cogan/complicaciones , Síndrome de Cogan/diagnóstico , Síndrome de Cogan/tratamiento farmacológico , Encefalitis/diagnóstico , Encefalitis/tratamiento farmacológico , Humanos , Inmunosupresores/uso terapéutico , Metilprednisolona/uso terapéuticoRESUMEN
A 49-year-old Japanese man with a 2-month history of a fever, headache, and bilateral conjunctival hyperemia was admitted. His condition fulfilled the giant cell arteritis classification criteria (new headache, temporal artery tenderness, elevated ESR) and atypical Cogan's syndrome (CS) with scleritis and sensorineural hearing loss (SNHL). The interleukin (IL)-6 serum level was extremely high. Two weeks after his insufficient response of SNHL and scleritis to oral prednisolone, we administered tocilizumab (TCZ); rapid improvements in scleritis and SNHL occurred. Early IL-6 target therapy can help prevent irreversible CS-induced sensory organ damage.
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Síndrome de Cogan , Arteritis de Células Gigantes , Pérdida Auditiva Sensorineural , Queratitis , Escleritis , Anticuerpos Monoclonales Humanizados , Apraxias/congénito , Síndrome de Cogan/diagnóstico , Síndrome de Cogan/tratamiento farmacológico , Arteritis de Células Gigantes/diagnóstico , Arteritis de Células Gigantes/tratamiento farmacológico , Cefalea , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/tratamiento farmacológico , Pérdida Auditiva Sensorineural/etiología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND/PURPOSE: Poretti-Boltshauser syndrome is a rare, nonprogressive neurologic syndrome with characteristic cerebellar cysts on neuroimaging due to mutations in LAMA1. The ophthalmic findings in Poretti-Boltshauser syndrome are not well described. Here, we report the ophthalmic findings from multimodal imaging and electrophysiology of a patient with genetically confirmed Poretti-Boltshauser syndrome. METHODS: A 3-year-old boy with confirmed mutations in LAMA1 underwent examination under anesthesia with electroretinography and multimodal imaging including fundus photography, fluorescein angiography, optical coherence tomography, and optical coherence tomography angiography. RESULTS: Dilated fundus examination was notable for retinal vascular anomalies, including a large area of nonperfusion in the temporal macula with corresponding retinal thinning on optical coherence tomography. There was an absence of a distinct foveal avascular zone and decreased density of both the superficial and deep vascular plexuses in the macula on optical coherence tomography angiography. There was diffuse loss of choriocapillaris architecture and decreased choroidal thickness. CONCLUSION: Patients with Poretti-Boltshauser syndrome may possess chorioretinal thinning and retinal vascular abnormalities appreciable on examination and multimodal imaging. These findings suggest a role for LAMA1 in retinal and choroidal vascular development.
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Anomalías Múltiples , Mácula Lútea , Apraxias/congénito , Preescolar , Síndrome de Cogan , Angiografía con Fluoresceína/métodos , Humanos , Masculino , Imagen Multimodal , Vasos Retinianos , Tomografía de Coherencia Óptica/métodos , Agudeza VisualRESUMEN
OBJECTIVE: For the first time, we administered reversing prism exposure to treat optic ataxia in a single patient with Balint-Holmes Syndrome (BHS), who also underwent specific trainings for simultanagnosia and ocular apraxia. METHOD AND RESULTS: By an introduction and withdrawal experimental design, we observed that the active treatment periods improved patient's visuospatial defects and functional autonomy. CONCLUSIONS: We thus provided a proof of principle supporting the use of reversing prism exposure in optic ataxia within an integrated and personalized rehabilitative approach for BHS.
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Apraxias , Trastornos de la Percepción , Accidente Cerebrovascular , Apraxias/congénito , Apraxias/etiología , Apraxias/terapia , Ataxia , Síndrome de Cogan , Movimientos Oculares , Humanos , Lóbulo Parietal , Trastornos de la Percepción/etiología , Trastornos de la Percepción/terapia , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/terapiaRESUMEN
PURPOSE: This study aimed to delineate the genetic basis of congenital ocular motor apraxia (COMA) in patients not otherwise classifiable. METHODS: We compiled clinical and neuroimaging data of individuals from six unrelated families with distinct clinical features of COMA who do not share common diagnostic characteristics of Joubert syndrome or other known genetic conditions associated with COMA. We used exome sequencing to identify pathogenic variants and functional studies in patient-derived fibroblasts. RESULTS: In 15 individuals, we detected familial as well as de novo heterozygous truncating causative variants in the Suppressor of Fused (SUFU) gene, a negative regulator of the Hedgehog (HH) signaling pathway. Functional studies showed no differences in cilia occurrence, morphology, or localization of ciliary proteins, such as smoothened. However, analysis of expression of HH signaling target genes detected a significant increase in the general signaling activity in COMA patient-derived fibroblasts compared with control cells. We observed higher basal HH signaling activity resulting in increased basal expression levels of GLI1, GLI2, GLI3, and Patched1. Neuroimaging revealed subtle cerebellar changes, but no full-blown molar tooth sign. CONCLUSION: Taken together, our data imply that the clinical phenotype associated with heterozygous truncating germline variants in SUFU is a forme fruste of Joubert syndrome.