RESUMO
Spinal muscular atrophy (SMA) is the second most frequent autosomal recessive disease characterized by degeneration of the anterior horn cells of the spinal cord, leading to muscular atrophy. SMA is classified into three types according to disease severity and age-onset: severe (type I), intermediate (type II) and mild (type III). Deletions in the survival motor neuron (SMN) gene, located in the chromosome region 5q11.2- 5q13.3, are major determinants of SMA phenotype. Extended deletions that include the neuronal apoptosis inhibitory protein (NAIP) gene may correlate with the severtity of SMA. SMN gene is present in two highly homologous copies, SMN1 and SMN2, but only deletions of the SMN1 gene (exons 7 and 8 or exon 7) are responsible for clinical manifestations of SMA. Here, we present the deletion profiling of SMN1 and NAIP genes in 89 children with SMA from Serbia: 52 patients with type I, 26 with type II, and 11 with type III. The homozygous deletion of the SMN1 gene was confirmed in 72 of 89 (81%) patients, being the most frequent in SMA type I (48/52): 68 patients (94.4%) with deletion of exons 7 and 8 and 4 patients (5.6%) with deletion of exon 7. The extended deletion including the NAIP gene was detected in 18 of 89 (20.2%) patients, mostly affected with type I. This study has revealed the lower incidence of deletions in the SMN1 and NAIP genes in families with SMA in Serbia and will provide important information for genetic counselling in these families.
Assuntos
Deleção de Genes , Testes Genéticos/métodos , Atrofia Muscular Espinal/epidemiologia , Atrofia Muscular Espinal/genética , Proteína Inibidora de Apoptose Neuronal/genética , Proteína 1 de Sobrevivência do Neurônio Motor/genética , Criança , Humanos , Incidência , Atrofia Muscular Espinal/classificação , Sérvia/epidemiologiaRESUMO
INTRODUCTION: Paroxysmal nonkinesigenic dyskinesia (PNKD) is a rare movement disorder characterized by sudden attacks of involuntary movements. Familial PNKD is an autosomal dominant trait, caused by mutations in the myofibrillogenesis regulator 1 (MR-1) gene on chromosome 2q35. Three different mutations have been described; all of them reside in the N-terminal region common to isoforms L and S, that has been suggested to code for a mitochondrial targeting sequence, necessary for the correct sub-cellular localization of the protein into mitochondria. METHODS: We report on four patients of the same family, affected by PNKD. Skin fibroblasts were used to analysed oxygen consumption and to measure mitochondrial matrix calcium response after agonist stimulation. Mitotracker-based visualization was also used to assess fragmentation of the mitochondrial network. RESULTS: the paroxysmal movements were dystonic in two patients and dystonic/choreiform in the other ones; in three cases the symptoms started in one limb and then generalized, while in one case remained focal. Three had a very early onset, within the first two years of life. The frequency of episodes showed a great variability, ranging from 2 times a day to 3 times a year, while the duration of the attacks ranged from 2 min to 1,5 h, always with sudden onset and end and complete recover in between. All affected subjects harbored a heterozygous C to T substitution in MR-1, causing an Ala9Val amino acid change in the N-terminal region. A significant reduction of oxygen consumption and altered calcium homeostasis were found in mutant fibroblasts compared to controls, while no difference was detected in mitochondrial network. CONCLUSIONS: The data on reduced oxygen consumption and altered calcium homeostasis obtained on mutant fibroblasts are the first evidences, in physiological conditions, of a mitochondrial dysfunction in PNKD.
Assuntos
Coreia/fisiopatologia , Doenças Mitocondriais/fisiopatologia , Adolescente , Adulto , Idade de Início , Sinalização do Cálcio/fisiologia , Células Cultivadas , Criança , Coreia/etiologia , Cromossomos Humanos Par 2/genética , Família , Feminino , Fibroblastos/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Doenças Mitocondriais/complicações , Transtornos dos Movimentos/etiologia , Proteínas Musculares/genética , Consumo de Oxigênio/fisiologia , Linhagem , Estudos Retrospectivos , Adulto JovemRESUMO
From 1972 to 2002, we diagnosed and treated 22 cases of subacute sclerosing panencephalitis. We report on two pediatric patients with fulminant subacute sclerosing panencephalitis who had atypical clinical manifestations. In both patients diagnosis was confirmed by elevated titers of CSF and serum antimeasles antibodies. Patient 1 presented with behavioral disorder, dysarthria, and drop attacks, while Patient 2 presented with partial complex seizures. Mental difficulties, personality changes, or myoclonus were not noticed in Patient 2. In both our patients stage I was not prominent, and stage II was of shortened duration. In spite of treatment with isoprinosine and interferon-alpha, both our patients deteriorated rapidly and died 2.5 and 4 months, respectively, after the onset of neurologic symptoms. Both atypical presentation and rapid clinical course observed in our patients could cause problems in making final diagnosis of subacute sclerosing panencephalitis. Therefore, subacute sclerosing panencephalitis should be included in differential diagnosis of acute unexplained encephalopathic diseases.
Assuntos
Panencefalite Esclerosante Subaguda/diagnóstico , Adolescente , Criança , Diagnóstico Diferencial , Evolução Fatal , Humanos , Masculino , Panencefalite Esclerosante Subaguda/fisiopatologiaRESUMO
The objective of the study was to evaluate etiology, clinical characteristics and outcome in children with epilepsia partialis continua (EPC). The investigation included 51 children with EPC aged 0.2-18 years treated in the period 1993-2009. The median period from the onset of underlying disorder to EPC was 6 months (0-72 months). EPC was caused by different pathologies: inflammatory and immune-mediated (52%), metabolic (13.7%), structural brain abnormalities (11.8%), cryptogenic (7.8%), vascular (5.9%), dual (5.9%), postoperative (2%). Median duration of EPC was 15 days (1-200 days). EPC involved more frequently the right side of the body comparing to the left one. The outcome was assessed at the end of the follow up period (mean 6.5 years, ranged 0.2-16 years). Unchanged neurological status was observed in 10 (19.6%) children, neurological consequences in 33 (64.7%) children and lethal outcome in 8 (15.7%) children. The most frequent etiology in our cohort was inflammatory and immune-mediated disease of central nerve system including Rasmussen's encephalitis. The duration of EPC was prolonged, most frequently involving the right upper limb. The outcome of EPC in children was unfavorable.
Assuntos
Epilepsia Parcial Contínua/diagnóstico , Epilepsia Parcial Contínua/etiologia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Encefalite/complicações , Encefalite/diagnóstico , Encefalite/epidemiologia , Epilepsia Parcial Contínua/epidemiologia , Seguimentos , Humanos , Doenças do Sistema Imunitário/complicações , Doenças do Sistema Imunitário/diagnóstico , Doenças do Sistema Imunitário/epidemiologia , Lactente , Estudos Retrospectivos , Resultado do TratamentoRESUMO
INTRODUCTION: West Syndrome involves epileptic encephalopathy in infants, occurring with an incidence of 5/10000 live births. Its main clinical feature are spasms that occur in clusters, which are associated with an EEG pattern called hypsarrhythmia and psychomotor retardation in most patients. West Syndrome is associated with many underlying conditions and the terms idiopathic, cryptogenic, and symptomatic are used for its aetiological subgroups. OBJECTIVE: The objective of this investigation was to determine the aetiological diagnosis of patients with West Syndrome and to compare the results with other studies. METHOD: In this 34-year longitudinal prospective one-centre study, 404 patients were studied. All patients exhibiting the diagnostic criteria for West Syndrome were investigated by clinical and neurological examination, EEG, ophthalmologic, psychological, metabolic, genetic, as well as neuroradiological methods, according to their particular indications. RESULTS: 36 (8.9%) patients had normal development, in whom infantile spasms occurred without any identifiable underlying cause, forming the idiopathic group. 51 patients (12.6%) with neurological impairment of unknown aetiology formed the cryptogenic group. The greatest number of patients (317 or 78.5%) formed the symptomatic group, in which neurological features and developmental delay preceded the onset of spasms. Disgenetic disorders and hereditary metabolic diseases were aetiological factors 44 (10.8%) patients. Prenatal and perinatal aetiological factors were revealed in one third of the patients (134 or 31%). Postnatal aetiological factors were revealed in 42 (10.2%) patients. In our study, disgenetic disorders were registered less frequently and perinatal complications more frequently than in other studies. CONCLUSION: Our results indicate the possibility of preventing West Syndrome with good quality obstetric and neonatal care, as well as the early prenatal diagnosis of brain malformations. Modern, sophisticated investigation makes the more accurate aetiological diagnosis of West Syndrome possible.
Assuntos
Espasmos Infantis/etiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Espasmos Infantis/diagnóstico , Espasmos Infantis/prevenção & controleRESUMO
Charcot-Marie-Tooth type 1A disease (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are common inherited disorders of the peripheral nervous system associated with duplication and deletion, respectively, of the 17p11.2 segment including the gene of peripheral myelin protein 22. We studied 48 subjects belonging to 29 families with clinical and electrophysiological signs of definite CMT1, 20 patients with suspected CMT phenotype, and 17 patients and healthy members of their families with HNPP. Blood sampling and DNA isolation, PCR, restriction analysis, southern blotting were performed using standard procedures. Of 48 patients with diagnosis of definite CMT1 in 25 (52%) we found a 1.5 Mb tandem duplication in chromosome 17p11.2. These duplications were not found in any of 20 sporadic cases with the clinical phenotype of CMT but without reliable electrophysiological data. Only 13 (44.8%) of 29 unrelated CMT1 patients from the first group had 17p11.2 duplications. Three of 4 sporadic cases (75%) with definite CMT1 had 17p11.2 duplications. Of 17 patients from 6 families with HNPP deletion of 17p11.2 segment was found in 15 (88.2%), as well as in 5 (83.3%) of six unrelated cases. Detection of CMT1A/HNPP recombination hotspot is a simple and reliable DNA diagnostic method, which is useful only for the patients with clinically already verified CMT1, and HNPP for further genetic counselling of patients and members of their families.