RESUMO
Mutations in PRRT2 have been described in paroxysmal kinesigenic dyskinesia (PKD) and infantile convulsions with choreoathetosis (PKD with infantile seizures), and recently also in some families with benign familial infantile seizures (BFIS) alone. We analyzed PRRT2 in 49 families and three sporadic cases with BFIS only of Italian, German, Turkish, and Japanese origin and identified the previously described mutation c.649dupC in an unstable series of nine cytosines to occur in 39 of our families and one sporadic case (77% of index cases). Furthermore, three novel mutations were found in three other families, whereas 17% of our index cases did not show PRRT2 mutations, including a large family with late-onset BFIS and febrile seizures. Our study further establishes PRRT2 as the major gene for BFIS alone.
Assuntos
Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Espasmos Infantis/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mutação , Linhagem , Convulsões Febris/genéticaRESUMO
Fukuyama-type congenital muscular dystrophy (FCMD) is an autosomal recessive disorder, characterized by severe muscular dystrophy associated with brain malformation. FCMD is the second most common form of muscular dystrophy and one of the most common autosomal recessive diseases among the Japanese population; however, no typical FCMD cases have been reported in any other population. In this study, we report on the first identification of a Chinese FCMD patient; our findings are supported by clinical, histological, and magnetic resonance imaging (MRI) evidence, as well as fukutin gene mutational analyses. The patient presented with neonatal hypotonia, seizures, and delayed motor and speech development. Additional testing revealed cerebral and cerebellar gyrus abnormalities with white matter signal intensity changes, elevated serum creatine kinase (CK) levels, and dystrophic skeletal muscle with alpha-dystroglycan hypoglycosylation, and normal beta-dystroglycan and merosin expression. Genetic analysis of the fukutin gene showed one copy with a Japanese founder 3-kilobase (kb) retrotransposal insertion in the 3'-non-coding region and the other copy with a known c.139C>T mutation. This is the first FCMD case reported in the Chinese population and the first case in which the 3-kb insertion has been found outside of the Japanese population. This report emphasizes the importance of considering the fukutin founder mutation for diagnostic purposes outside of Japan.
Assuntos
Povo Asiático/genética , Proteínas de Membrana/genética , Distrofias Musculares/congênito , Distrofias Musculares/genética , Mutagênese Insercional/genética , Retroelementos/genética , Sequência de Bases , Pré-Escolar , Análise Mutacional de DNA , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Dados de Sequência Molecular , Músculo Esquelético/patologia , Linhagem , Coloração e RotulagemRESUMO
Fukuyama congenital muscular dystrophy (FCMD) is a unique autosomal recessively inherited condition which is characterized by a combination of systemic progressive muscular dystrophy (PMD), severe cerebrocerebellar cortical malformation in association with/without retinal derrangement of very early onset. FCMD is the second most prevalent type of PMD in Japan, while it is extremely rare outside Japan. Historically, the first half of the 20th century was a dark age in terms of CMD. The entity of CMD was practically absent in the international classification of PMD until 1986, when MIM first enlisted FCMD as a disease entity. In the midst of this dark age, that is, in 1960, we first reported a series of 15 cases of CMD and advocated that this will represent a completely new disease entity. To reach a correct diagnosis, a key role was played by keen clinical observation, application of newly explored diagnostic procedures, including muscle biopsy, needle electromyography and determination of serum creatine kinase activities. Another important factor was an exhaustive review of pertinent literature. Through exercising the above approaches in combination, we could reach to our conviction that we are dealing with a entirely new type of CMD.
Assuntos
Distrofias Musculares/história , Epônimos , História do Século XX , História do Século XXI , Humanos , Distrofias Musculares/congênitoRESUMO
In 1980s, the authors experienced 5 patients with "a peculiar form of acute encephalitis/encephalopathy "which is characterized by three features: 1. Complex partial seizures with secondary generalization recur incessantly or continue persistently without regaining consciousness for many days in spite of intensive diazepam (DZP) therapy; usually general anesthesia at ICU setting for 2-3 weeks becomes mandatory. 2. After weaning from long-run anesthesia, seizures of the same type still persist, though much less frequent, during the convalescent and chronic phases of the disease throughout. There is no seizure-free interval between the acute and chronic stages. 3. Etiology is totally unknown;extensive laboratory examinations mostly remain within normal ranges, though clinical features such as acute onset, frequent accompaniment of fever, etc., mimic those of acute encephalitis/encephalopathy. The synopsis of our 5 patients were; age ranged from 2 to 5 years old, no antecedent history of seizures, fever of moderate degree preceded seizures a few days and persisted in the acute stage; complex partial seizures with secondary generalization recurred several times every hour. Circulatory/respiratory compromise necessitated a drastic intervention with barbiturate coma at ICU. Etiology was unknown. Follow-up for 19 years in average revealed mental retardation and chronic epilepsies in all patients. Since our first report in 1987, 49 similar cases with ours have been sporadically reported. The majority of the reported cases had been submitted to longstanding general anesthesia and placed in barbiturate coma for weeks to 2 months. The death occurred in 7 patients. In all reported cases, the first line drugs such as DZP iv, phenytoin iv, etc did not work, and it was highly recommended to place the patient under barbiturate coma as early as possible.
Assuntos
Encefalite/complicações , Epilepsia Parcial Complexa/etiologia , Estado Epiléptico/etiologia , Doença Aguda , Adolescente , Anticonvulsivantes/administração & dosagem , Barbitúricos/administração & dosagem , Criança , Pré-Escolar , Diagnóstico Diferencial , Diagnóstico Precoce , Encefalite/diagnóstico , Epilepsia Parcial Complexa/diagnóstico , Epilepsia Parcial Complexa/tratamento farmacológico , Feminino , Seguimentos , Humanos , Lactente , Infusões Intravenosas , Masculino , Prognóstico , Recidiva , Estado Epiléptico/diagnóstico , Estado Epiléptico/tratamento farmacológicoRESUMO
Paroxysmal kinesigenic choreoathetosis (PKC) is presently clearly designated as a familial movement disorder with autosomal dominant inheritance. We identified a family of PKC, in which 6 out of 23 members were affected, and 4 of the affected members had a history of infantile convulsions. Thus, this family was also considered as a case of infantile convulsions with paroxysmal choreoathetosis (ICCA). Video-EEG monitoring of two affected members suggested that PKC is less likely to be a form of reflex epilepsy, despite the existence of a history of infantile convulsions. Linkage analysis on eight Japanese families, including this family, defined the locus of PKC within the pericentromeric region of chromosome 16. ICCA and a form of autosomal dominant benign familial infantile convulsions (BFIC) were both mapped to the same or nearby region for PKC on chromosome 16. Additionally and quite unexpectedly, the locus of wet/dry ear wax (cerumen) was found to be located in the same region. Lastly, it was pointed out that the priority of the first discovery of PKC in the world should go to a Japanese psychiatrist, Shuzo Kure (1865-1932), who published the first detailed and almost complete description of a male patient with PKC in a Japanese medical journal in 1892.
Assuntos
Atetose/genética , Coreia/genética , Epilepsia/genética , Atetose/diagnóstico , Atetose/história , Cerume , Coreia/diagnóstico , Coreia/história , Diagnóstico Diferencial , Eletroencefalografia , Epilepsia/diagnóstico , Ligação Genética , História do Século XX , Humanos , Lactente , Japão , Linhagem , Prognóstico , Gravação em VídeoAssuntos
Hormônio Adrenocorticotrópico/uso terapêutico , Espasmos Infantis/tratamento farmacológico , Hormônio Adrenocorticotrópico/administração & dosagem , Anticonvulsivantes/uso terapêutico , Cosintropina/uso terapêutico , Comparação Transcultural , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Humanos , Lactente , Japão , Resultado do Tratamento , Estados Unidos , Vigabatrina/uso terapêuticoRESUMO
We report a 12-year-old boy with idiopathic torsion dystonia. Blepharospasm appeared at the age of 10, followed by truncal hypertonia and progressive scoliosis after 1 year. He had bizarre involuntary movement of his limbs upon waking, which was initially misinterpreted as a psychogenic reaction. Routine neurological examinations revealed no abnormality. Treatment with diazepam, bacrophen, 1-dopa, and clonazepam, led to only short time improvement of symptoms. At the age of 14, his symptoms gradually improved in natural course. At present he is 15 years old, and capable of normal daily activities. His clinical course was not typical of idiopathic torsion dystonia and very rare in children.
Assuntos
Blefarospasmo/etiologia , Distonia Muscular Deformante/complicações , Blefarospasmo/fisiopatologia , Criança , Distonia Muscular Deformante/fisiopatologia , Eletromiografia , Humanos , MasculinoAssuntos
Eletroencefalografia/métodos , Epilepsias Mioclônicas/fisiopatologia , Idade de Início , Mapeamento Encefálico , Diagnóstico Diferencial , Eletroencefalografia/classificação , Epilepsias Mioclônicas/epidemiologia , Epilepsias Mioclônicas/genética , Epilepsias Mioclônicas/terapia , Epilepsia Tipo Ausência/fisiopatologia , Feminino , Lateralidade Funcional/fisiologia , Humanos , Lactente , Recém-Nascido , Masculino , Mortalidade , Desempenho Psicomotor/fisiologia , Convulsões/classificação , Convulsões/fisiopatologia , Síndrome , Resultado do TratamentoAssuntos
Epilepsias Mioclônicas/genética , Mutação , Proteínas do Tecido Nervoso/genética , Canais de Sódio/genética , Temperatura Corporal/fisiologia , Estudos de Coortes , Eletroencefalografia/classificação , Eletroencefalografia/métodos , Epilepsias Mioclônicas/epidemiologia , Epilepsias Mioclônicas/fisiopatologia , Epilepsias Mioclônicas/terapia , Epilepsia Reflexa/fisiopatologia , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Japão/epidemiologia , Japão/etnologia , Masculino , Transtornos Mentais/fisiopatologia , Canal de Sódio Disparado por Voltagem NAV1.1 , Fenótipo , Resultado do TratamentoRESUMO
Congenital muscular dystrophy (CMD) is a newly established group of progressive muscular dystrophy, comprising a number of new entities, including Fukuyama congenital muscular dystrophy (FCMD). Victor Dubowitz (1997) wrote that to go back to the "dark ages", when there was still no CMD, we do not need to go back all that far; in the 1960s, many people were not recognizing the existence of CMD or in fact actively denying it. In 1960, Fukuyama and his colleagues published a short report of 15 CMD cases, delineating 9 clinical diagnostic criteria. In 1961, he presented detailed features of 25 cases at a formal national convention of Japanese Society of Neurology, the essence of which was widely approved by Japanese colleagues. The situation in foreign countries was quite different, however; its international recognition as a unique independent entity delayed till early 1980s. Eventually, FCMD was enlisted in MIM as OMIM 253800 in 1986, and in WHO's ICD-10 NA as G71.084 in 1990 for the first time. Toda et al localized a responsible FCMD gene at 9q31-33 in 1993 and identified fukutin gene in 1998. Another revolution took place in 1994, that is, laminin 2 deficiency was first identified in Western CMD patients by Tomé et al in 1994. This discovery gave a great impact to Western investigators, because in Western population, this condition is prevalent while FCMD was practically non-existent. World literature survey revealed that 1,963 articles on CMD had been published since 1893 till 2006, composing from 726 papers contributed by Japanese authors and 1,137 papers by non-Japanese authors. For the period 2001-2006, contribution by non-Japanese authors dramatically increased, occupying 66% of the total. Anyhow, the discovery of FCMD is worth as a historical landmark in dual sense. First, it convinced world authorities the fact the CMD is a real component of the muscular dystrophies family. Second, it provided a new concept on pathogenesis of muscular dystrophies in general, emphasizing multisystemic involvement rather than muscle alone.
Assuntos
Distrofias Musculares/história , Bibliometria , História do Século XX , Humanos , Japão , Proteínas de Membrana/genética , Distrofias Musculares/classificação , Distrofias Musculares/congênito , Distrofias Musculares/genética , MutaçãoRESUMO
BACKGROUND: A 6-year-old girl with Rasmussen syndrome (RS) showed multiple small high-signal-intensity areas independently in the right hemisphere by fluid-attenuated inversion recovery (FLAIR) imaging on magnetic resonance imaging (MRI) 1 year after the onset of epilepsy. METHODS: MRI performed 4 months later demonstrated a further increase in the number of these foci and enlargement in the size of the previous FLAIR lesions. RESULTS: An [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) study showed a strong, spotty uptake in the right temporooccipital regions, corresponding to the sites of continuous EEG seizure discharges. In contrast, [11C]methionine PET demonstrated multifocal uptake regions, which corresponded anatomically to the FLAIR lesions, suggesting sites of underlying chronic inflammation. CONCLUSIONS: These neuroimaging findings suggested that the inflammatory process in RS spreads either multifocally at the same time, as seen in this case, or from one discrete area to the adjacent region, as reported previously.
Assuntos
Córtex Cerebral/fisiopatologia , Dominância Cerebral/fisiologia , Encefalite/diagnóstico , Epilepsia Motora Parcial/diagnóstico , Epilepsia do Lobo Temporal/diagnóstico , Aumento da Imagem , Imageamento por Ressonância Magnética , Tomografia Computadorizada de Emissão , Doenças do Sistema Nervoso Autônomo/diagnóstico , Radioisótopos de Carbono , Córtex Cerebral/patologia , Criança , Progressão da Doença , Encefalite/patologia , Encefalite/fisiopatologia , Epilepsia Parcial Contínua/diagnóstico , Epilepsia Parcial Contínua/patologia , Epilepsia Parcial Contínua/fisiopatologia , Epilepsia , Epilepsia Motora Parcial/patologia , Epilepsia Motora Parcial/fisiopatologia , Epilepsia do Lobo Temporal/patologia , Epilepsia do Lobo Temporal/fisiopatologia , Feminino , Fluordesoxiglucose F18 , Seguimentos , Humanos , Metionina , Lobo Occipital/patologia , Lobo Occipital/fisiopatologia , Lobo Temporal/patologia , Lobo Temporal/fisiopatologiaRESUMO
PURPOSE: Benign familial infantile convulsions (BFIC) is a form of idiopathic epilepsy. It is characterized by clusters of afebrile seizures occurring around the sixth month of life. The disease has a benign course with a normal development and rare seizures in adulthood. Previous linkage analyses defined three susceptibility loci on chromosomes 19q12-q13.11, 16p12-q12, and 2q23-31. However, a responsible gene has not been identified. We studied linkage in 16 further BFIC families. METHODS: We collected 16 BFIC families, without an additional paroxysmal movement disorder, of German, Turkish, or Japanese origin with two to eight affected individuals. Standard two-point linkage analysis was performed. RESULTS: The clinical picture included a large variety of seizure semiologies ranging from paleness and cyanosis with altered consciousness to generalized tonic-clonic seizures. Interictal EEGs showed focal epileptiform discharges in six patients, and three ictal EEGs in three distinct patients revealed a focal seizure onset in different brain regions. In all analyzed families, we found no evidence for linkage to the BFIC loci on chromosomes 19q and 2q, as well as to the known loci for benign familial neonatal convulsions on chromosomes 8q and 20q. In 14 of the families, the chromosome 16 locus could be confirmed with a cumulative maximum two-point lod score of 6.1 at marker D16S411, and the known region for BFIC could be narrowed to 22.5 Mbp between markers D16S690 and D16S3136. CONCLUSIONS: Our data confirm the importance of the chromosome 16 locus for BFIC and may narrow the relevant interval.