RESUMO
OBJECTIVES: Depending on patient age at onset, absence epilepsy is subdivided into childhood and juvenile forms. Absence seizures can occur several times per day (pyknoleptic course) or less frequently than daily (non-pyknoleptic course). Seizures typically terminate before adulthood, but a quarter of patients need ongoing treatment beyond adolescence. Little is known about their long-term seizure and psychosocial outcome. METHODS: Files of 135 outpatients with absence epilepsy (76 females; 123 had additional generalised tonic-clonic seizures) were retrospectively analysed after a median follow-up of 45.4 years (IQR: 31.9-56.2). Eighty-two subjects completed an additional interview. Patients were dichotomised according to age at epilepsy onset (childhood: n=82; juvenile: n=53) and course of absence seizures (pyknoleptic: n=80; non-pyknoleptic: n=55). RESULTS: Among all patients, 53% achieved 5-year terminal seizure remission, 16% without antiepileptic medication. Median age at last seizure was lower in patients with childhood onset of absence epilepsy (37.7 years) versus juvenile onset (44.4 years; P≤0.01). However, rates and duration of terminal seizure remission were similar. Pyknoleptic versus non-pyknoleptic course of absence seizures made no difference for long-term seizure outcome. Multivariate analysis identified only higher age at investigation to be associated with terminal 5-year seizure remission. Regarding aspects of psychosocial outcome, there were no significant differences between the respective subgroups. CONCLUSIONS: These data indicate that if absence epilepsy persists beyond adolescence, long-term seizure and psychosocial outcome do not differ between childhood and juvenile onset or between pyknoleptic and non-pyknoleptic course of absence epilepsy. However, higher patient age increases the chance of terminal seizure remission.
Assuntos
Epilepsia Tipo Ausência/epidemiologia , Adolescente , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Epilepsia Tipo Ausência/diagnóstico , Epilepsia Tipo Ausência/terapia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Remissão Espontânea , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVE: Until now, it has been unclear if the three subsyndromes of adolescent-onset generalized genetic epilepsy (GGE) differ in long-term prognosis. Therefore, this study aimed to compare long-term seizure outcome in juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), and epilepsy with generalized tonic-clonic seizures alone (EGTCS). METHODS: This retrospective study is based on the archive of an institutional tertiary care outpatient clinic for adult patients with epilepsy. Charts of 870 epilepsy outpatients were reviewed among whom 176 had adolescent-onset GGE (53 JAE, 66 JME, 57 EGTCS). Median patient age at investigation was 60 years; median follow-up time was 42.5 years. If possible, GGE patients were additionally interviewed on psychosocial and clinical variables. RESULTS: Age at first seizure was significantly higher in EGTCS patients (median 18 years) than in patients with JAE or JME (14 years each; p ≤ 0.001). Long-term seizure outcome hardly differed between the three subsyndromes. At the end of follow-up, 60% of all patients were in 5-year terminal seizure remission, and in 14%, epilepsy even had resolved (>10 years without seizures, >5 years without pharmacotherapy). Twenty percent of patients had persistent seizures during the last year of follow-up. Across all patients, 23% reported a psychiatric comorbidity, 87% had married, and 57% had achieved university entrance qualification. SIGNIFICANCE: Long-term outcome was shown to be highly similar across all subsyndromes of adolescent-onset GGE. Even in a selection of difficult-to-treat epilepsy patients still attending an adult epilepsy clinic, most become seizure-free. To confirm these findings, prospective studies are needed.
Assuntos
Epilepsia Tipo Ausência/diagnóstico , Epilepsia Tipo Ausência/genética , Epilepsia Generalizada/diagnóstico , Epilepsia Generalizada/genética , Epilepsia Tônico-Clônica/diagnóstico , Epilepsia Tônico-Clônica/genética , Epilepsia Mioclônica Juvenil/diagnóstico , Epilepsia Mioclônica Juvenil/genética , Adolescente , Adulto , Anticonvulsivantes/uso terapêutico , Epilepsia Tipo Ausência/tratamento farmacológico , Epilepsia Generalizada/tratamento farmacológico , Epilepsia Tônico-Clônica/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Epilepsia Mioclônica Juvenil/tratamento farmacológico , Prognóstico , Estudos RetrospectivosRESUMO
PURPOSE: Juvenile myoclonic epilepsy (JME) is a well-defined subsyndrome of idiopathic generalized/genetic epilepsy. It is allegedly related to specific personality characteristics and has been associated with unfavorable social outcome. We aimed to analyze psychosocial outcome in patients with JME. To delineate consequences of the chronic seizure disorder from possible neurobiologic contributions being inherent to the condition itself, we compared social outcome in JME subjects with that of age- and sex-matched control patients with absence epilepsy (AE). METHODS: Patients with an epilepsy course of at least 20 years were included. All JME and AE patients (n = 41 in each group) answered a structured questionnaire asking about seizures, treatment, and psychosocial variables. In addition, patients with JME were assessed with the Quality of Life in Epilepsy Inventory 31 (QOLIE-31). RESULTS: In JME, 46.3 years (20-69) after onset of epilepsy, the overall psychosocial long-term outcome was favorable (80.5% of patients had never been unemployed for more than 1 year, 90.2% were well integrated into social context). Quality of life in all inquired subdomains revealed high scores. Compared with AE controls, JME patients did not perform worse regarding psychosocial outcome; rate of university access and degrees in JME patients was even higher (70% vs. 34%, p = 0.001). JME patients showed a high level of quality of life, and current or previous psychiatric comorbidity was associated significantly with lower overall quality of life scores (p = 0.02). SIGNIFICANCE: Our long-term study on JME patients demonstrated favorable psychosocial outcome that contrasted previous findings. This is the first study to compare social outcome in JME with another genetically determined form of epilepsy. Similar outcomes in JME and AE patients argue against specific neurobiologic alterations in JME that may predispose to social deficits. In JME, reduced quality of life seems to be associated with psychiatric comorbidity.
Assuntos
Epilepsia Mioclônica Juvenil/psicologia , Qualidade de Vida , Adulto , Idoso , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Epilepsia Mioclônica Juvenil/epidemiologia , Inventário de Personalidade , Tempo , Adulto JovemRESUMO
Epilepsy with grand mal on awakening (EGMA) is a well-defined subtype of idiopathic generalized epilepsy. Patients with follow-up of at least 20 years were assessed retrospectively regarding 5-year terminal seizure remission. Forty-two patients were included (mean age=60 ± 13 years). After follow-up of 40 ± 13 years, 26 patients (62%) were in remission, 5 without antiepileptic drugs. Age at investigation (odds ratio=0.939, 95% confidence interval=0.887-0.994, p=0.029) independently predicted lacking remission. Nineteen patients (45.2%) had withdrawn from antiepileptic drugs at least once; 12 of those (63.2%) had seizure relapse. EGMA has a favorable long-term prognosis. With increasing age and treatment duration, antiepileptic drug withdrawal may be justified.
Assuntos
Estado Epiléptico/complicações , Estado Epiléptico/epidemiologia , Resultado do Tratamento , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/uso terapêutico , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Comportamento Social , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/mortalidadeRESUMO
OBJECTIVES: Juvenile myoclonic epilepsy (JME) is the most common idiopathic generalized epilepsy subsyndrome, contributing to approximately 3% to 11% of adolescent and adult cases of epilepsy. However, little is known about the long-term medical evolution of this clinical entity. The aim of this study was to analyze long-term outcome in a clinically well-defined series of patients with JME for seizure evolution and predictors of seizure outcome. METHODS: In this retrospective cohort study, we analyzed seizure outcome in 66 patients who had JME, were treated at the Department of Neurology, Charité-Universitätsmedizin Berlin, and were initially diagnosed by a single senior epileptologist. RESULTS: After a mean follow-up time of 44.6 years (20-69 years), 59.1% of patients remained free of seizures for at least 5 years before the last contact. Among the seizure-free patients, 28 (71.8%) were still taking antiepileptic drugs and 11 (28.2%) were off medication for at least the last 5 years. We identified manifestation of additional absence seizures at onset of JME as an independent predictor of an unfavorable outcome regarding seizure freedom. CONCLUSIONS: A significant proportion of patients with JME were seizure-free and off antiepileptic drug therapy in the later course of their disorder. Patients with JME and additional absence seizures might represent a different JME subtype with a worse outcome.
Assuntos
Epilepsia Mioclônica Juvenil/diagnóstico , Epilepsia Mioclônica Juvenil/epidemiologia , Convulsões/diagnóstico , Convulsões/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/uso terapêutico , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Epilepsia Mioclônica Juvenil/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Convulsões/tratamento farmacológicoRESUMO
The treatment of status epilepticus has changed over the past five decades since the first colloquium on status epilepticus, held in Marseille in 1962. New intravenous drugs, such as valproate, levetiracetam, lacosomide or ketamine and new routes of administration, such as intranasal or bucal, as well as high-class randomized clinical trials in the prehospital setting and early stages of status have changed the field. However it is remarkable, how the basic principles and difficulties of treatment of status epilepticus have remained the same. This article is as a translation of a narrative review authored by Dieter Janz at the Marseille Colloquium 1962, published in 1967. The medical practice and all available treatment at that time have been reviewed critically in the article. The translation of the original French article has been kept as close as possible to the original, to give a detailed account on the treatment of status at that time.
Assuntos
Anticonvulsivantes/uso terapêutico , Estado Epiléptico/história , Anticonvulsivantes/administração & dosagem , História do Século XIX , História do Século XX , Humanos , Infusões Intravenosas , Convulsões/tratamento farmacológico , Estado Epiléptico/tratamento farmacológico , Resultado do TratamentoRESUMO
An international workshop on juvenile myoclonic epilepsy (JME) was conducted in Avignon, France in May 2011. During that workshop, a group of 45 experts on JME, together with one of the founding fathers of the syndrome of JME ("Janz syndrome"), Prof. Dr. Dieter Janz from Berlin, reached a consensus on diagnostic criteria and management of JME. The international experts on JME proposed two sets of criteria, which will be helpful for both clinical and scientific purposes. Class I criteria encompass myoclonic jerks without loss of consciousness exclusively occurring on or after awakening and associated with typical generalized epileptiform EEG abnormalities, with an age of onset between 10 and 25. Class II criteria allow the inclusion of myoclonic jerks predominantly occurring after awakening, generalized epileptiform EEG abnormalities with or without concomitant myoclonic jerks, and a greater time window for age at onset (6-25years). For both sets of criteria, patients should have a clear history of myoclonic jerks predominantly occurring after awakening and an EEG with generalized epileptiform discharges supporting a diagnosis of idiopathic generalized epilepsy. Patients with JME require special management because their epilepsy starts in the vulnerable period of adolescence and, accordingly, they have lifestyle issues that typically increase the likelihood of seizures (sleep deprivation, exposure to stroboscopic flashes in discos, alcohol intake, etc.) with poor adherence to antiepileptic drugs (AEDs). Results of an inventory of the different clinical management strategies are given. This article is part of a supplemental special issue entitled Juvenile Myoclonic Epilepsy: What is it Really?
Assuntos
Consenso , Gerenciamento Clínico , Epilepsia Mioclônica Juvenil/diagnóstico , Epilepsia Mioclônica Juvenil/terapia , Humanos , Cooperação InternacionalRESUMO
Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% and account for 20-30% of all epilepsies. Despite their high heritability of 80%, the genetic factors predisposing to GGEs remain elusive. To identify susceptibility variants shared across common GGE syndromes, we carried out a two-stage genome-wide association study (GWAS) including 3020 patients with GGEs and 3954 controls of European ancestry. To dissect out syndrome-related variants, we also explored two distinct GGE subgroups comprising 1434 patients with genetic absence epilepsies (GAEs) and 1134 patients with juvenile myoclonic epilepsy (JME). Joint Stage-1 and 2 analyses revealed genome-wide significant associations for GGEs at 2p16.1 (rs13026414, P(meta) = 2.5 × 10(-9), OR[T] = 0.81) and 17q21.32 (rs72823592, P(meta) = 9.3 × 10(-9), OR[A] = 0.77). The search for syndrome-related susceptibility alleles identified significant associations for GAEs at 2q22.3 (rs10496964, P(meta) = 9.1 × 10(-9), OR[T] = 0.68) and at 1q43 for JME (rs12059546, P(meta) = 4.1 × 10(-8), OR[G] = 1.42). Suggestive evidence for an association with GGEs was found in the region 2q24.3 (rs11890028, P(meta) = 4.0 × 10(-6)) nearby the SCN1A gene, which is currently the gene with the largest number of known epilepsy-related mutations. The associated regions harbor high-ranking candidate genes: CHRM3 at 1q43, VRK2 at 2p16.1, ZEB2 at 2q22.3, SCN1A at 2q24.3 and PNPO at 17q21.32. Further replication efforts are necessary to elucidate whether these positional candidate genes contribute to the heritability of the common GGE syndromes.
Assuntos
Epilepsia Generalizada/genética , Estudo de Associação Genômica Ampla , Alelos , Epilepsia Tipo Ausência/genética , Predisposição Genética para Doença/genética , Proteínas de Homeodomínio/genética , Humanos , Epilepsia Mioclônica Juvenil/genética , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Proteínas Serina-Treonina Quinases/genética , Receptor Muscarínico M3/genética , Proteínas Repressoras/genética , Homeobox 2 de Ligação a E-box com Dedos de ZincoRESUMO
PURPOSE: Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% with heritability estimates of 80%. A considerable proportion of families with siblings affected by GGEs presumably display an oligogenic inheritance. The present genome-wide linkage meta-analysis aimed to map: (1) susceptibility loci shared by a broad spectrum of GGEs, and (2) seizure type-related genetic factors preferentially predisposing to either typical absence or myoclonic seizures, respectively. METHODS: Meta-analysis of three genome-wide linkage datasets was carried out in 379 GGE-multiplex families of European ancestry including 982 relatives with GGEs. To dissect out seizure type-related susceptibility genes, two family subgroups were stratified comprising 235 families with predominantly genetic absence epilepsies (GAEs) and 118 families with an aggregation of juvenile myoclonic epilepsy (JME). To map shared and seizure type-related susceptibility loci, both nonparametric loci (NPL) and parametric linkage analyses were performed for a broad trait model (GGEs) in the entire set of GGE-multiplex families and a narrow trait model (typical absence or myoclonic seizures) in the subgroups of JME and GAE families. KEY FINDINGS: For the entire set of 379 GGE-multiplex families, linkage analysis revealed six loci achieving suggestive evidence for linkage at 1p36.22, 3p14.2, 5q34, 13q12.12, 13q31.3, and 19q13.42. The linkage finding at 5q34 was consistently supported by both NPL and parametric linkage results across all three family groups. A genome-wide significant nonparametric logarithm of odds score of 3.43 was obtained at 2q34 in 118 JME families. Significant parametric linkage to 13q31.3 was found in 235 GAE families assuming recessive inheritance (heterogeneity logarithm of odds = 5.02). SIGNIFICANCE: Our linkage results support an oligogenic predisposition of familial GGE syndromes. The genetic risk factor at 5q34 confers risk to a broad spectrum of familial GGE syndromes, whereas susceptibility loci at 2q34 and 13q31.3 preferentially predispose to myoclonic seizures or absence seizures, respectively. Phenotype- genotype strategies applying narrow trait definitions in phenotypic homogeneous subgroups of families improve the prospects of disentangling the genetic basis of common familial GGE syndromes.
Assuntos
Cromossomos Humanos Par 13/genética , Cromossomos Humanos Par 2/genética , Epilepsia Generalizada/genética , Predisposição Genética para Doença/genética , Mapeamento Cromossômico , Família , Feminino , Ligação Genética , Loci Gênicos , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Linhagem , FenótipoRESUMO
Juvenile myoclonic epilepsy is the most frequent idiopathic generalized epilepsy syndrome. It is characterized by predominant myoclonic jerks of upper limbs, often provoked by cognitive activities, and typically responsive to treatment with sodium valproate. Neurophysiological, neuropsychological and imaging studies in juvenile myoclonic epilepsy have consistently pointed towards subtle abnormalities in the medial frontal lobes. Using functional magnetic resonance imaging with an executive frontal lobe paradigm, we investigated cortical activation patterns and interaction between cortical regions in 30 patients with juvenile myoclonic epilepsy and 26 healthy controls. With increasing cognitive demand, patients showed increasing coactivation of the primary motor cortex and supplementary motor area. This effect was stronger in patients still suffering from seizures, and was not seen in healthy controls. Patients with juvenile myoclonic epilepsy showed increased functional connectivity between the motor system and frontoparietal cognitive networks. Furthermore, we found impaired deactivation of the default mode network during cognitive tasks with persistent activation in medial frontal and central regions in patients. Coactivation in the motor cortex and supplementary motor area with increasing cognitive load and increased functional coupling between the motor system and cognitive networks provide an explanation how cognitive effort can cause myoclonic jerks in juvenile myoclonic epilepsy. The supplementary motor area represents the anatomical link between these two functional systems, and our findings may be the functional correlate of previously described structural abnormalities in the medial frontal lobe in juvenile myoclonic epilepsy.
Assuntos
Mapeamento Encefálico , Encéfalo/irrigação sanguínea , Transtornos Cognitivos/etiologia , Epilepsia Mioclônica Juvenil/complicações , Epilepsia Mioclônica Juvenil/patologia , Adulto , Encéfalo/patologia , Estudos de Casos e Controles , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética/métodos , Masculino , Testes Neuropsicológicos , Oxigênio/sangue , Adulto JovemRESUMO
Professor J.A.N. Corsellis, whose life and work is recalled here, gained great insight into the meaning of morphological cerebral aberrations found in neuropsychiatric disease through exact neuropathological investigations of tissue specimens obtained from patients with distinct syndromes. He was a leading authority in the field. We have searched and compiled resources relating to J.A.N. Corsellis' life and work, including personal memories from colleagues and data from scientific publications. J.A.N. Corsellis made seminal contributions to the understanding of neuropsychiatric disease; his works substantially added to the understanding of the dementias, schizophrenia and the psychoses, and morphological sequelae of boxing. In seizure disorders, his name is linked to the first description of focal cortical dysplasia and limbic encephalitis, the pathology of status epilepticus and Ammon's horn sclerosis, and the systematic investigation of epilepsy surgery specimens in general. Both his life and work are closely linked to Runwell Hospital, Wickford, Essex and the Maudsley Hospital. During his professional life he established a large brain bank, now known as the Corsellis Collection. J.A.N. Corsellis had significant impact on neuroscience; many of his observations were groundbreaking and are still valid.
Assuntos
Epilepsia/história , Epilepsia/patologia , Neurociências/história , Transtornos Psicóticos/história , Transtornos Psicóticos/patologia , Córtex Cerebral/patologia , Alemanha , História do Século XX , Humanos , Londres , Livros de Texto como Assunto , Bancos de Tecidos/história , Reino UnidoAssuntos
Canais de Cloreto/genética , Epilepsia Generalizada/genética , Variação Genética , Canais de Cloro CLC-2 , Impressões Digitais de DNA , Análise Mutacional de DNA , Eletrofisiologia , Epilepsia Generalizada/patologia , Epilepsia Generalizada/fisiopatologia , Saúde da Família , Feminino , Genes Dominantes , Predisposição Genética para Doença , Testes Genéticos , Heterozigoto , Humanos , Masculino , LinhagemRESUMO
Idiopathic generalized epilepsy (IGE) is an inherited neurological disorder affecting about 0.4% of the world's population. Mutations in ten genes causing distinct forms of idiopathic epilepsy have been identified so far, but the genetic basis of many IGE subtypes is still unknown. Here we report a gene associated with the four most common IGE subtypes: childhood and juvenile absence epilepsy (CAE and JAE), juvenile myoclonic epilepsy (JME), and epilepsy with grand mal seizures on awakening (EGMA; ref. 8). We identified three different heterozygous mutations in the chloride-channel gene CLCN2 in three unrelated families with IGE. These mutations result in (i) a premature stop codon (M200fsX231), (ii) an atypical splicing (del74-117) and (iii) a single amino-acid substitution (G715E). All mutations produce functional alterations that provide distinct explanations for their pathogenic phenotypes. M200fsX231 and del74-117 cause a loss of function of ClC-2 channels and are expected to lower the transmembrane chloride gradient essential for GABAergic inhibition. G715E alters voltage-dependent gating, which may cause membrane depolarization and hyperexcitability.
Assuntos
Canais de Cloreto/genética , Epilepsia Generalizada/genética , Mutação , Adolescente , Adulto , Sequência de Bases , Membrana Celular/metabolismo , Códon de Terminação , Análise Mutacional de DNA , DNA Complementar/metabolismo , Eletrofisiologia , Saúde da Família , Feminino , Heterozigoto , Humanos , Masculino , Microscopia Confocal , Microscopia de Fluorescência , Modelos Biológicos , Dados de Sequência Molecular , Linhagem , Plasmídeos/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , TransfecçãoRESUMO
PURPOSE: A recent genome-wide scan revealed a major susceptibility locus for idiopathic generalized epilepsies (IGEs) in the chromosomal region 8p12 in 32 IGE families without members with juvenile myoclonic epilepsy (JME). This study explored the presence of an IGE locus in the chromosomal region 8p12. METHODS: Our study included 176 multiplex families of probands with common IGE syndromes. Parametric and nonparametric multipoint linkage analyses were carried out between the IGE trait and six microsatellite polymorphisms encompassing the putative susceptibility locus. To explore the associated phenotype-genotype relation, two distinct subgroups of families were selected by the presence (n = 64) or absence (n = 112) of a family member with JME. To adjust the phenotypic spectrum toward adolescent-onset IGEs, a third subgroup of 28 families without JME was chosen through an IGE proband with seizure onset at age 10-20 years. RESULTS: Parametric and nonparametric multipoint linkage analyses provided no evidence for linkage between IGE and markers encompassing the putative IGE locus in the chromosomal region 8p12. Furthermore, we found no hint of linkage along the candidate region in any of the three family subgroups. CONCLUSIONS: We failed to provide evidence for a major IGE locus in the chromosomal region 8p12. On the contrary, these parametric linkage results provide strong evidence against linkage across the candidate region under a broad range of genetic models. If there is a susceptibility locus for IGE in the chromosomal region 8p12, then the size of the effect or the proportion of linked families is too small to detect linkage in the investigated family sample.
Assuntos
Mapeamento Cromossômico , Cromossomos Humanos Par 8 , Epilepsia Generalizada/genética , Predisposição Genética para Doença/classificação , Adulto , Alelos , Criança , Repetições de Dinucleotídeos , Epilepsia Tipo Ausência/genética , Epilepsia Tônico-Clônica/genética , Europa (Continente) , Feminino , Frequência do Gene/genética , Marcadores Genéticos/genética , Genótipo , Humanos , Escore Lod , Masculino , Modelos Genéticos , Epilepsia Mioclônica Juvenil/genética , Fenótipo , Polimorfismo Genético , SíndromeRESUMO
A recent genome-wide scan showed strong evidence for a major locus for common syndromes of idiopathic generalized epilepsy (IGE) at the marker D18S474 on chromosome 18q21.1 (LOD score 4.5/5.2 multipoint/two-point). The present replication study tested the presence of an IGE locus in the chromosomal region 18q21.1. Our linkage study included 130 multiplex families of probands with common IGE syndromes. Eleven microsatellite polymorphisms encompassing a candidate region of 30 cM on either side of the marker D18S474 were genotyped. The two-point homogeneity LOD score for D18S474 showed strong evidence against linkage at the original linkage peak (Z = -18.86 at theta(m = f) = 0.05), assuming a recessive mode of inheritance with 50% penetrance. Multipoint parametric heterogeneity LOD scores < -2 were obtained along the candidate region when proportions of linked families greater than 35% were assumed under recessive inheritance. Furthermore, non-parametric multipoint linkage analyses showed no hint of linkage throughout the candidate region (P > 0.19). Accordingly, we failed to support evidence for a major IGE locus in the chromosomal region 18p11-18q23. If there is a susceptibility locus for IGE in this region then the size of the effect or the proportion of linked families is too small to detect linkage in the investigated family sample.
Assuntos
Cromossomos Humanos Par 18/genética , Epilepsia Generalizada/genética , Predisposição Genética para Doença , Adolescente , Adulto , Idade de Início , Criança , Mapeamento Cromossômico , Suscetibilidade a Doenças , Epilepsias Mioclônicas/genética , Feminino , Ligação Genética , Marcadores Genéticos , Humanos , Escore Lod , Masculino , Repetições de Microssatélites/genética , Modelos Genéticos , Núcleo Familiar , Polimorfismo GenéticoRESUMO
Los EEG de 80 progenitores con epilepsia y actividad electroencefalográfica focal fueron comparados, inter e intrafamiliarmente, con los de sus 135 hijos de 0 a 19 años de edad. Las alteraciones focales consideradas fueron ondas lentas, theta y delta, puntas y puntas lentas aisladas o seguidas de onda lenta. El 8.9% de los hijos presentaron como sus padres EEG con foco, en tanto que el 12.5% de las 80 familias fueron familias semejantes, en las que por lo menos un hijo tenía actividad focal como su progenitor. El sexo de los padres y el de sus hijos no demostró ser una variable significativa en la aparición de las semejanzas electroencefalográficas. Se discuten los resultados obtenidos haciendo notar la escasa literatura existente sobre el tema y la necesidad de tomar con precaución dichos resultados, por cuanto sólo algunas de las numerosas variables que pueden incidir en ellos fueron controladas en la presente investigación