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AIM: This exploratory study evaluates rating scale usage by experts from the European Reference Network for Rare Neurological Diseases (ERN-RND) for paediatric MD, considering factors like diagnosis, intellectual disability, age, and transition to adult care. The aim is to propose a preliminary framework for consistent application. METHODS: A multicentre survey among 25 ERN-RND experts from 10 European countries examined rating scale usage in paediatric MD, categorizing MD into acute, non-progressive, and neurodegenerative types. Factors influencing scale choice and the transition to adult care practices were analysed. A comprehensive literature search was conducted to identify the earliest age of application of these scales in paediatric patients. RESULTS: The study identifies various rating scales and establishes their usage frequencies for different MDs. Experts highlighted the need for standardized scales and proposed preliminary evaluation strategies based on clinical contexts. Challenges in applying scales to young, non-cooperative patients were acknowledged. INTERPRETATION: The study recommends developing standardized rating scales for paediatric MDs to improve evaluations and data collection. It suggests potential scales for specific clinical scenarios to better evaluate disease progression. Comprehensive, patient-centred care remains crucial during the transition to adult care, despite the identified challenges. This exploratory approach aims to enhance patient outcomes and care.
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This study presents an in-depth analysis of mitochondrial enzyme activities in Friedreich's ataxia (FA) patients, focusing on the Electron Transport Chain complexes I, II, and IV, the Krebs Cycle enzyme Citrate Synthase, and Coenzyme Q10 levels. It examines a cohort of 34 FA patients, comparing their mitochondrial enzyme activities and clinical parameters, including disease duration and cardiac markers, with those of 17 healthy controls. The findings reveal marked reductions in complexes II and, specifically, IV, highlighting mitochondrial impairment in FA. Additionally, elevated Neurofilament Light Chain levels and cardiomarkers were observed in FA patients. This research enhances our understanding of FA pathophysiology and suggests potential biomarkers for monitoring disease progression. The study underscores the need for further clinical trials to validate these findings, emphasizing the critical role of mitochondrial dysfunction in FA assessment and treatment.
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Biomarcadores , Ataxia de Friedreich , Ubiquinona , Humanos , Ataxia de Friedreich/diagnóstico , Masculino , Adulto , Biomarcadores/metabolismo , Femenino , Ubiquinona/análogos & derivados , Adulto Joven , Persona de Mediana Edad , Citrato (si)-Sintasa/metabolismo , Mitocondrias/metabolismo , Adolescente , Estudios de CohortesRESUMEN
Deterioration of dynamic visual acuity (DVA) as a result of impaired vestibulo-ocular reflex (VOR) has been well described in peripheral vestibulopathies, however, changes in DVA in patients with degenerative cerebellar ataxias (CA) and its relation to VOR impairment in these patients has not yet been evaluated. Our aim was to assess the alterations of DVA in CA and to evaluate its relation to vestibular function. 32 patients with CA and 3 control groups: 13 patients with unilateral and 13 with bilateral vestibulopathy and 21 age matched healthy volunteers were examined by clinical DVA test, VOR was assessed by video Head Impulse Test and caloric irrigation. The severity of ataxia in CA was assessed by Scale for the assessment and rating of ataxia (SARA). Relationship between DVA and vestibular function in CA patients was examined by linear regressions. DVA impairment was highly prevalent in CA patients (84%) and its severity did not differ between CA and bilateral vestibulopathy patients. The severity of DVA impairment in CA was linked mainly to VOR impairment and only marginally to the degree of ataxia. However, DVA impairment was present also in CA patients without significant vestibular lesion showing that central mechanisms such as impairment of central adaptation of VOR are involved. We suggest that the evaluation of DVA should be a standard part of clinical evaluation in patients with progressive CA, as this information can help to target vestibular and oculomotor rehabilitation.
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Ataxia Cerebelosa , Enfermedades Vestibulares , Prueba de Impulso Cefálico , Humanos , Reflejo Vestibuloocular , Agudeza VisualRESUMEN
BACKGROUND: Tay-Sachs disease (TSD) is an inherited neurodegenerative disorder caused by a lysosomal ß-hexosaminidase A deficiency due to mutations in the HEXA gene. The late-onset form of disease (LOTS) is considered rare, and only a limited number of cases have been reported. The clinical course of LOTS differs substantially from classic infantile TSD. METHODS: Comprehensive data from 14 Czech patients with LOTS were collated, including results of enzyme assays and genetic analyses. RESULTS: 14 patients (9 females, 5 males) with LOTS were diagnosed between 2002 and 2018 in the Czech Republic (a calculated birth prevalence of 1 per 325,175 live births). The median age of first symptoms was 21 years (range 10-33 years), and the median diagnostic delay was 10.5 years (range 0-29 years). The main clinical symptoms at the time of manifestation were stammering or slurred speech, proximal weakness of the lower extremities due to anterior horn cell neuronopathy, signs of neo- and paleocerebellar dysfunction and/or psychiatric disorders. Cerebellar atrophy detected through brain MRI was a common finding. Residual enzyme activity was 1.8-4.1% of controls. All patients carried the typical LOTS-associated c.805G>A (p.Gly269Ser) mutation on at least one allele, while a novel point mutation, c.754C>T (p.Arg252Cys) was found in two siblings. CONCLUSION: LOTS seems to be an underdiagnosed cause of progressive distal motor neuron disease, with variably expressed cerebellar impairment and psychiatric symptomatology in our group of adolescent and adult patients. The enzyme assay of ß-hexosaminidase A in serum/plasma is a rapid and reliable tool to verify clinical suspicions.
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Cerebelo/diagnóstico por imagen , Trastornos Mentales/diagnóstico por imagen , Atrofia Muscular/diagnóstico por imagen , Enfermedad de Tay-Sachs/diagnóstico por imagen , Adolescente , Adulto , Edad de Inicio , Estudios de Cohortes , República Checa/epidemiología , Femenino , Humanos , Masculino , Trastornos Mentales/epidemiología , Trastornos Mentales/psicología , Persona de Mediana Edad , Atrofia Muscular/epidemiología , Atrofia Muscular/psicología , Enfermedad de Tay-Sachs/epidemiología , Enfermedad de Tay-Sachs/psicología , Adulto JovenRESUMEN
OBJECTIVE: We examined the presence of cerebellar symptoms in ADHD and their association with behavioral markers of this disorder. METHOD: Sixty-two children with ADHD and 62 typically developing (TD) children were examined for cerebellar symptoms using the ataxia rating scale and tested using Conners' Continuous Performance Test. RESULTS: Children with ADHD had significantly more cerebellar symptoms compared with the TD children. Cerebellar symptom scores decreased with age in the ADHD group; in the TD group remained stable. In both groups, cerebellar symptoms were associated with parent-rated hyperactive/impulsive symptoms, variability of response time standard error (RT-SE) and increase of RT-SE as the test progresses. More variables were associated with cerebellar symptoms in the ADHD group including omission errors, overall RT-SE and its increase for prolonged interstimulus intervals. CONCLUSION: Our results highlight the importance of research into motor functions in children with ADHD and indicate a role for cerebellar impairment in this disorder.
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Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Encefalopatías/fisiopatología , Cerebelo/fisiopatología , Adolescente , Niño , Femenino , Humanos , Hipercinesia/fisiopatología , Conducta Impulsiva/fisiología , Masculino , Pruebas Neuropsicológicas , Trastornos Psicomotores/fisiopatología , Tiempo de Reacción/fisiología , Corteza Sensoriomotora/fisiologíaRESUMEN
Spinocerebellar ataxia type 28 (SCA28) is an autosomal dominant neurodegenerative disorder caused by missense AFG3L2 mutations. To examine the occurrence of SCA28 in the Czech Republic, we screened 288 unrelated ataxic patients with hereditary (N = 49) and sporadic or unknown (N = 239) form of ataxia for mutations in exons 15 and 16, the AFG3L2 mutation hotspots. A single significant variant, frameshift mutation c.1958dupT leading to a premature termination codon, was identified in a patient with slowly progressive speech and gait problems starting at the age of 68 years. Neurological examination showed cerebellar ataxia, mild Parkinsonian features with predominant bradykinesia, polyneuropathy of the lower limbs, and cognitive decline. However, other common SCA28 features like pyramidal tract signs (lower limb hyperreflexia, positive Babinski sign), ophthalmoparesis or ptosis were absent. The mutation was also found in a patient's unaffected daughter in whom a targeted examination at 53 years of age revealed mild imbalance signs. RNA analysis showed a decreased ratio of the transcript from the mutated AFG3L2 allele relative to the normal transcript in the peripheral lymphocytes of both patients. The ratio was increased by puromycin treatment, indicating that the mutated transcript can be degraded via nonsense-mediated RNA decay. The causal link between the mutation and the phenotype of the patient is currently unclear but a pathogenic mechanism based on AFG3L2 haploinsufficiency rather than the usual dominant-negative effect of missense AFG3L2 mutations reported in SCA28, cannot be excluded.
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Proteasas ATP-Dependientes/genética , Mutación del Sistema de Lectura/genética , Predisposición Genética a la Enfermedad/genética , Ataxias Espinocerebelosas/genética , Degeneraciones Espinocerebelosas/genética , ATPasas Asociadas con Actividades Celulares Diversas , Anciano , República Checa , Femenino , Humanos , Oftalmoplejía/genética , Fenotipo , Ataxias Espinocerebelosas/diagnósticoRESUMEN
Spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative disorders currently associated with 27 genes. The most frequent types are caused by expansions in coding CAG repeats. The frequency of SCA subtypes varies among populations. We examined the occurrence of rare SCAs, SCA8, SCA12, SCA17 and dentatorubro-pallidoluysian atrophy (DRPLA), in the Czech population from where the data were missing. We analyzed causal gene expansions in 515 familial and sporadic ataxic patients negatively tested for SCA1-3 and SCA6-7. Pathogenic SCA8 and SCA17 expansions were identified in eight and five patients, respectively. Tay-Sachs disease was later diagnosed in one patient with an SCA8 expansion and the diagnosis of multiple sclerosis (MS) was suspected in two other patients with SCA8 expansions. These findings are probably coincidental, although the participation of SCA8 expansions in the susceptibility to MS and disease progression cannot be fully excluded. None of the patients had pathogenic SCA12 or DRPLA expansions. However, three patients had intermediate SCA12 alleles out of the normal range with 36 and 43 CAGs. Amyotrophic lateral sclerosis (ALS) was probable in the patient with 43 CAGs. This coincidence is remarkable, especially in the context with the recently identified predisposing role of longer SCA2 alleles in ALS. Five families with SCA17 represent a significant portion of ataxic patients and this should be reflected in the diagnostics of SCAs in the Czech population. SCA8 expansions must be considered after careful clinical evaluation.
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Epilepsias Mioclónicas Progresivas , Proteínas del Tejido Nervioso/genética , Ataxias Espinocerebelosas , Repeticiones de Trinucleótidos/genética , Esclerosis Amiotrófica Lateral/genética , República Checa/epidemiología , Análisis Mutacional de ADN , Salud de la Familia , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Esclerosis Múltiple , Epilepsias Mioclónicas Progresivas/epidemiología , Epilepsias Mioclónicas Progresivas/genética , Ataxias Espinocerebelosas/clasificación , Ataxias Espinocerebelosas/epidemiología , Ataxias Espinocerebelosas/genéticaRESUMEN
OBJECTIVES: Cognitive disorders and dementia occur in 19 to 42% of patients with spinocerebellar ataxia type 2 (SCA2). Neuropsychological tests can reveal executive dysfunction, impaired visual and verbal memory, tongue and speech impairment, attention disorders and impaired verbal fluency. METHODS: We performed psychiatric and neuropsychological examinations in 12 patients diagnosed with genetically confirmed SCA2 and 12 healthy volunteers matching the patients in age, gender, and length of education. The level of motor impairment was determined using the brief ataxia rating scale (BARS). The neuropsychological examination focused on testing executive functions, short-term visual and verbal memory, attention, psychomotor tempo, visual motor coordination, learning ability and comprehension ability. The tests were divided into two subgroups according to the difficulty of motor tasks. The cognitive abilities composite score (CACS) was determined by calculating the arithmetic mean of T scores of the respective tests. RESULTS: Patients with SCA2 had significantly lower CACSs (p=0.00005) compared to the healthy volunteers. Patients exhibited impaired performance in both difficult and simple motor tests. The severity of cognitive impairment was related to the age at the onset of the disease (p=0.002) but not to the duration or to the overall BARS score. CONCLUSIONS: Compared to healthy volunteers, patients with SCA2 exhibited significantly worse cognitive performance in all areas tested, including the tests of simple motor tasks. Moreover, the cognitive performance of patients worsened as the difficulty of the motor tasks increased.
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Trastornos del Conocimiento/psicología , Cognición/fisiología , Ataxias Espinocerebelosas/psicología , Adulto , Edad de Inicio , Atención/fisiología , Trastornos del Conocimiento/etiología , Función Ejecutiva , Femenino , Humanos , Aprendizaje/fisiología , Masculino , Memoria/fisiología , Persona de Mediana Edad , Pruebas Neuropsicológicas , Desempeño Psicomotor/fisiología , Ataxias Espinocerebelosas/complicaciones , Ataxias Espinocerebelosas/genética , Percepción Visual/fisiologíaRESUMEN
Reports of visual functional impairment in spinocerebellar ataxia type 2 (SCA2) have been studied previously using pattern reversal visually evoked potentials (VEPs) with contradictory results. To provide additional evidence to this area, visual functions were studied using VEPs and event-related potentials (ERPs) in a group of ten patients with genetically verified SCA2. The electrophysiological examination included pattern reversal and motion-onset VEPs as well as visually driven oddball ERPs with an evaluation of a target and a pre-attentive response. In six patients, we found abnormal visual/cognitive processing that differed from normal values in latency, but not in the amplitude of the dominant VEP/ERP peaks. Among the VEPs/ERPs used, the motion-onset VEPs exhibited the highest sensitivity and showed a strong Spearman correlation to SCA2 duration (from r = 0.82 to r = 0.90, p < 0.001) and clinical state assessed by Brief Ataxia Rating Scale (from r = 0.71 (p = 0.022) to r = 0.80 (p < 0.001)). None of the VEP/ERP latencies showed a correlation to the triplet repeats of the SCA2 gene. In three patients, we did not find any visual/cognitive pathology, and one subject showed only a single subtle prolongation of the VEP peak. The observed visual/cognitive deficit was related to the subjects' clinical state and the illness duration, but no relationship to the genetic marker of SCA2 was found. From the VEP/ERP types used, the motion-onset VEPs seems to be the most promising candidate for clinical state monitoring rather than a tool for early diagnostic use.
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Ataxias Espinocerebelosas/fisiopatología , Ataxias Espinocerebelosas/psicología , Percepción Visual/fisiología , Adulto , Edad de Inicio , Anciano , Envejecimiento/fisiología , ADN/genética , Electroencefalografía , Fenómenos Electrofisiológicos , Potenciales Evocados/fisiología , Potenciales Evocados Visuales/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Examen Neurológico , Reconocimiento Visual de Modelos/fisiología , Estimulación Luminosa , Procesamiento de Señales Asistido por Computador , Ataxias Espinocerebelosas/genética , Repeticiones de Trinucleótidos , Corteza Visual/fisiopatología , Adulto JovenRESUMEN
OBJECTIVES: Autism is a severe neurodevelopmental disorder with a high rate of epilepsy and subclinical epileptiform activity. High physical connectivity on a microcolumnar level leading to epileptiform activity and low functional informational connectivity are assumed in autism. The aim of this study was to investigate nonlinear EEG brain dynamics in terms of synchronization in a group of children with autism spectrum disorders compared to a control group. We expected a lower degree of synchronization in autistic subjects. METHODS: The autistic group consisted of 27 patients with autism spectrum disorders diagnosed according to ICD-10. The mean age of the sample was 7.1 (SD 3.6) years, 14 of them were mentally retarded. Normal EEG was found in 9 patients, epileptiform EEG in 18 autistic patients. Four patients had a history of epileptic seizures, fully compensated in long term. The control group consisted of 20 children (mean age of 8.4, SD 2.3 years) with normal intelligence, without an epileptic history, investigated within the frame of the research program for cochlear implantation. They had normal neurological examination and suffered from perceptive deafness. Normal EEG was found in 17 of the control subjects, epileptiform EEG was in 3 control subjects. We analyzed night sleep EEG recordings from 10 channels (F3, F4, F7, F8, C3, C4, T3, T4, P3 and P4) with the inclusion of sleep stages NREM 2, 3 and 4 in the subsequent analyses. Coarse-grained entropy information rates between neighbouring electrodes were computed, expressing the synchronization between 11 selected electrode couples. RESULTS: Synchronization was significantly lower in the autistic group in all three examined NREM stages even when age and intelligence were taken into account as covariates. CONCLUSIONS: The results of the study confirmed the validity of the underconnectivity model in autism.
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Trastorno Autístico/fisiopatología , Electroencefalografía , Sueño/fisiología , Niño , Preescolar , Humanos , Discapacidad Intelectual/fisiopatología , PolisomnografíaRESUMEN
Rett syndrome (RTT), an X-linked dominant neurodevelopmental disorder in females, is caused mainly by de novo mutations in the methyl-CpG-binding protein 2 gene (MECP2). Here we report mutation analysis of the MECP2 gene in 87 patients with RTT from the Czech and Slovak Republics, and Ukraine. The patients, all girls, with classical RTT were investigated for mutations using bi-directional DNA sequencing and conformation sensitive gel electrophoresis analysis of the coding sequence and exon/intron boundaries of the MECP2 gene. Restriction fragment length polymorphism analysis was performed to confirm the mutations that cause the creation or abolition of the restriction site. Mutation-negative cases were subsequently examined by multiple ligation-dependent probe amplification (MLPA) to identify large deletions. Mutation screening revealed 31 different mutations in 68 patients and 12 non-pathogenic polymorphisms. Six mutations have not been previously published: two point mutations (323T>A, 904C>T), three deletions (189_190delGA, 816_832del17, 1069delAGC) and one deletion/inversion (1063_1236del174;1189_1231inv43). MLPA analysis revealed large deletions in two patients. The detection rate was 78.16%. Our results confirm the high frequency of MECP2 mutations in females with RTT and provide data concerning the mutation heterogeneity in the Slavic population.
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Proteína 2 de Unión a Metil-CpG/genética , Síndrome de Rett/genética , Análisis Mutacional de ADN , Europa Oriental , Femenino , Humanos , Mutación , Polimorfismo Genético , Población Blanca/genéticaRESUMEN
OBJECTIVES: In contrast to most human autosomal genes which are expressed biallelically, the expression of imprinted genes depends on the parental origin of the allele. Prader-Willi syndrome is a neurobehavioral disorder in which the expression of active paternal alleles of imprinted genes from chromosomal region 15q11-q13 is abolished by deletions, maternal uniparental disomy or imprinting defects. We report an unusual case of maternal uniparental disomy of chromosome 15 due to a balanced translocation t(8;15)(q24.1;q21.2) leading to Prader-Willi syndrome in a 3-year-old girl. METHODS AND RESULTS: Cytogenetic investigation revealed a balanced translocation t(8;15)(q24.1;q21.2) in the patient and subsequently also in her unaffected mother. Fluorescence in situ hybridization analysis did not reveal any deletion of the PWS critical region, but methylation analysis of the SNRPN gene showed an abnormal methylation pattern indicating the absence of paternal chromosome 15. Microsatellite analysis of multiple loci and methylation-specific MLPA analysis confirmed maternal uniparental heterodisomy of chromosome 15 as the cause of PWS in the patient. CONCLUSIONS: This example emphasizes the importance of uniparental disomy testing in pregnancies of carriers of chromosomal aberrations with participation of chromosomes carrying imprinted genes involved in human diseases.
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Síndrome de Prader-Willi/genética , Translocación Genética , Disomía Uniparental/genética , Preescolar , Cromosomas Humanos Par 15 , Cromosomas Humanos Par 8 , Análisis Citogenético , Metilación de ADN , Femenino , Humanos , Hibridación Fluorescente in Situ , Repeticiones de MicrosatéliteRESUMEN
We report on a family with spinocerebellar ataxia type 1 (SCA1), in which the age at onset and the severity of the disease do not correlate with the number of CAG repeat units. Although a marked anticipation was observed in the proband, it was not a consequence of an expansion of the CAG tract. None of the expanded alleles contained CAT interruptions. The pathologic expansion in this family was stable during the paternal but not maternal transmission, where it expanded by one trinucleotide and unexpectedly did not lead to anticipation. Our observations suggest that factors other than the length of the CAG repeat play a considerable role in determination of the disease course.
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Ataxias Espinocerebelosas/genética , Expansión de Repetición de Trinucleótido , Adulto , Edad de Inicio , Anciano , Alelos , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Reacción en Cadena de la Polimerasa , Ataxias Espinocerebelosas/patologíaRESUMEN
Hallervorden-Spatz disease (HSD) was and is known as a rare disorder primarily characterized by progressive extrapyramidal dysfunction and dementia alongside optic nerve atrophy or retinal degeneration and pyramidal signs. The rate of occurence of HSD is thus far unknown. Progress in DNA diagnostics stirred up a nomenclature and from HSD, or, perhaps better put, the Hallervorden-Spatz syndrome, crystallized the pantothenate kinase-associated neurodegeneration (PKAN) as a clearly defined entity on the level of DNA. In this paper, we present our first results and experience in the diagnosis of PKAN in the Czech Republic and discuss questions related to differential diagnosis.
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Ganglios Basales/patología , Neurodegeneración Asociada a Pantotenato Quinasa/genética , Neurodegeneración Asociada a Pantotenato Quinasa/patología , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Adolescente , Adulto , Calcinosis/genética , Calcinosis/patología , Niño , Preescolar , República Checa , Diagnóstico Diferencial , Discinesias/genética , Discinesias/patología , Salud de la Familia , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , MutaciónRESUMEN
Differential diagnosis in neurologic patients with spinocerebellar syndrome is complex as a result of the great degree of variability in phenotypic and genetic aspects of more than 200 nosological entities. In the past decade, genetic etiology has been discovered in part of the diseases and the term ''spinocerebellar ataxia'' has become, from a neurologic point of view, a loose definition applied to a group of autosomal dominant diseases. Topical extensive literature about differential diagnoses of ataxias usually refers to genetics classification or is produced by a group of radiologists, elektrophysiologists and biologists as well as others in the field. A further problem is that the majority of studies do not take into account other acquired illnesses and diseases which may fundamentally alter the symptomology and course of a primary disease, not to mention the possibility of concomitancy in hereditary diseases. The following article was prompted by daily contact with ataxic patients and related issues raised by colleagues; its goal is to clarify problems faced by child neurologists and neurologists in clinical practice.
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Árboles de Decisión , Ataxias Espinocerebelosas/diagnóstico , Ataxias Espinocerebelosas/genética , Niño , Preescolar , Protocolos Clínicos , Diagnóstico Diferencial , Salud de la Familia , Humanos , Ataxias Espinocerebelosas/clasificación , Degeneraciones Espinocerebelosas/clasificación , Degeneraciones Espinocerebelosas/diagnóstico , Degeneraciones Espinocerebelosas/genética , SíndromeRESUMEN
DNA testing broadens diagnostic tools available for hereditary ataxias. However, together with current knowledge of genes and their mutations crop up new phenotype figures of diseases already well known. Diagnostic problems in practice can consist in part due to the very similar symptoms of hereditary ataxias and acquaintance in or availability of new techniques such as DNA testing and result in misdiagnosis. We present a case study of a 57 year-old woman with both expansion of the triplet repetitive sequence of FRDA gene and a premutation in FMR1 gene. At present we diagnose her with Very Late Onset Friedreich s ataxia, but we advise of possible combinations or aggravations of her symptoms due to manifestation of Fragile X premutation tremor/ataxia syndrome. In nontypical phenotypes of DNA verifying hereditary ataxias we recommend searching of comorbidity, specifically from a range of hereditary ataxias with very similar spectra of symptoms.
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Ataxia de Friedreich/genética , Proteínas de Unión a Hierro/genética , Mutación/fisiología , Proteínas del Tejido Nervioso/genética , Proteínas de Unión al ARN/genética , ADN/genética , Femenino , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil , Síndrome del Cromosoma X Frágil/complicaciones , Síndrome del Cromosoma X Frágil/genética , Ataxia de la Marcha/etiología , Humanos , Persona de Mediana Edad , Fenotipo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Repeticiones de Trinucleótidos/genética , FrataxinaRESUMEN
The aim of the study was to investigate the potential association of epilepsy and EEG abnormalities with autistic regression and mental retardation. We examined a group of 77 autistic children (61 boys, 16 girls) with an average age of 9.1 +/- 5.3 years. Clinical interview, neurological examination focused on the evaluation of epilepsy, IQ testing, and 21-channel EEG (including night sleep EEG recording) were performed. Normal EEGs were observed in 44.4% of the patients, non-epileptiform abnormal EEGs in 17.5%, and abnormal EEGs with epileptiform discharges in 38.1% of the patients. Epilepsy was found in 22.1% of the subjects. A history of regression was reported in 25.8% of the patients, 54.8% of the sample had abnormal development during the first year of life, and 79.7% of the patients were mentally retarded. Autistic regression was significantly more frequent in patients with epilepsy than in non-epileptic patients (p = 0.003). Abnormal development during the first year of life was significantly associated with epileptiform EEG abnormalities (p = 0.014). Epilepsy correlated significantly with mental retardation (p = 0.001). Although the biological basis and possible causal relationships of these associations remain to be explained, they may point to different subgroups of patients with autistic spectrum disorders.