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The term "Gilles de la Tourette syndrome", or the more commonly used term "Tourette syndrome" (TS) refers to the association of motor and phonic tics which evolve in a context of variable but frequent psychiatric comorbidity. The syndrome is characterized by the association of several motor tics and at least one phonic tic that have no identifiable cause, are present for at least one year and appear before the age of 18. The presence of coprolalia is not necessary to establish or rule out the diagnosis, as it is present in only 10% of cases. The diagnosis of TS is purely clinical and is based on the symptoms defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). No additional tests are required to confirm the diagnosis of TS. However, to exclude certain differential diagnoses, further tests may be necessary. Very frequently, one or more psychiatric comorbidities are also present, including attention deficit hyperactivity disorder, obsessive-compulsive disorder, anxiety, explosive outbursts, self-injurious behaviors, learning disorders or autism spectrum disorder. The condition begins in childhood around 6 or 7 years of age and progresses gradually, with periods of relative waxing and waning of tics. The majority of patients experience improvement by the end of the second decade of life, but symptoms may persist into adulthood in around one-third of patients. The cause of TS is unknown, but genetic susceptibility and certain environmental factors appear to play a role. The treatment of TS and severe forms of tics is often challenging and requires a multidisciplinary approach (involving the general practitioner (GP), pediatrician, psychiatrist, neurologist, school or occupational physicians, psychologist and social workers). In mild forms, education (of young patients, parents and siblings) and psychological management are usually recommended. Medical treatments, including antipsychotics, are essential in the moderate to severe forms of the disease (i.e. when there is a functional and/or psychosocial discomfort linked to tics). Over the past decade, cognitive-behavioral therapies have been validated for the treatment of tics. For certain isolated tics, botulinum toxin injections may also be useful. Psychiatric comorbidities, when present, often require a specific treatment. For very severe forms of TS, treatment by deep brain stimulation offers real therapeutic hope. If tics are suspected and social or functional impairment is significant, specialist advice should be sought, in accordance with the patient's age (psychiatrist/child psychiatrist; neurologist/pediatric neurologist). They will determine tic severity and the presence or absence of comorbidities. The GP will take over the management and prescription of treatment: encouraging treatment compliance, assessing side effects, and combating stigmatization among family and friends. They will also play an important role in rehabilitation therapies, as well as in ensuring that accommodations are made in the patient's schooling or professional environment.
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BACKGROUND: Tuberous sclerosis complex (TSC) is a genetic disorder involving the TSC1 or TSC2 gene. Skin signs are prominent, but dermatological data are scarce. This study aims to describe the cutaneous signs of TSC with the genotype. METHODS: We studied the dermatological characteristics of 38 patients with TSC at the University Hospital of Montpellier. We collected details of genotypic features. RESULTS: All the patients presented at least one cutaneous sign. The dermatological examination alone was sufficient to establish a definite diagnosis of TSC based on the diagnostic criteria for 34/38 patients. No association was found between cutaneous signs and the presence of a TSC1 or TSC2 mutation. We noted skin signs that were poorly described in the disease, namely epidermal nevus in 3 patients, vascular malformation in 2 patients, and keratosis pilaris in 9 patients. DISCUSSION: While several studies demonstrate a more severe neurological phenotype in TSC2 mutated patients, skin expression does not appear to differ according to the mutated gene. Further case reports and molecular genetic studies are needed to determine the link between epidermal nevus, vascular malformations, keratosis pilaris and TSC.
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Esclerose Tuberosa , Humanos , Mutação , Estudos Prospectivos , Esclerose Tuberosa/genética , Proteína 1 do Complexo Esclerose Tuberosa/genética , Proteína 2 do Complexo Esclerose Tuberosa/genética , Proteínas Supressoras de Tumor/genéticaRESUMO
BACKGROUND AND PURPOSE: Childhood-onset autosomal dominant cerebellar ataxia type 7 (SCA7) is a severe disease which leads to premature loss of ambulation and death. Early diagnosis of SCA7 is of major importance for genetic counselling and still relies on specific genetic testing, driven by clinical expertise. However, the precise phenotype and natural history of paediatric SCA7 has not yet been fully described. Our aims were to describe the natural history of SCA7 in a large multicentric series of children of all ages, and to find correlates to variables defining this natural history. METHODS: We collected and analysed clinical data from 28 children with proven SCA7. All had clinical manifestations of SCA7 and either a definite number of CAG repeats in ATXN7 or a long expansion > 100 CAG. RESULTS: We identified four clinical presentation patterns related to age at onset. Children of all age groups had cerebellar atrophy and retinal dystrophy. Our data, combined with those in the literature, suggest that definite ranges of CAG repeats determine paediatric SCA7 subtypes. The number of CAG repeats inversely correlated to all variables of the natural history. Age at gait ataxia onset correlated accurately to age at loss of walking ability and to age at death. CONCLUSION: SCA7 in children has four presentation patterns that are roughly correlated to the number of CAG repeats. Our depiction of the natural history of SCA7 in children may help in monitoring the effect of future therapeutic trials.
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Ataxias Espinocerebelares , Ataxina-7 , Criança , Testes Genéticos , Humanos , Fenótipo , Ataxias Espinocerebelares/diagnóstico , Ataxias Espinocerebelares/genéticaRESUMO
BACKGROUND: Acute transverse myelitis (ATM) in children is a rare and often severe disease for which there are few known prognostic factors, particularly the subsequent risk of multiple sclerosis (MS) diagnosis. OBJECTIVES: To determine the clinical course and prognostic factors after a first episode of ATM in children. METHODS: Thirty children below 16 years of age diagnosed with a first neurological episode of ATM were included retrospectively. Clinical evaluation, treatment, laboratory, and MRI data were collected. RESULTS: Median age at onset was 11 years (range 3-15 years). Follow-up data were available for a median of 4 years (range 0.5-16.7 years). Five patients subsequently had a diagnosis of MS (17%), which was associated with acute partial transverse myelitis (odds ratio 5; 95% confidence interval 2.3-11), with a 60% probability of having a relapse at five years (p < 0.01). The 2011 Verhey criteria correctly identified MS in children with the highest specificity (96%) and sensitivity (80%). CONCLUSION: Acute partial transverse myelitis and brain MRI abnormalities at initial presentation are significantly predictive of a subsequent diagnosis of MS in children with ATM. These findings suggest that closer brain MRI monitoring after acute partial transverse myelitis might make the earlier introduction of disease-modifying therapies possible.
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Encéfalo/patologia , Esclerose Múltipla/diagnóstico , Mielite Transversa/diagnóstico , Medula Espinal/patologia , Doença Aguda , Adolescente , Idade de Início , Criança , Pré-Escolar , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Esclerose Múltipla/complicações , Mielite Transversa/etiologia , Prognóstico , Estudos Retrospectivos , RiscoRESUMO
Management of childhood dystonia differs in certain respects from that of adult dystonia: (i) childhood dystonia is more often secondary than primary; (ii) mixed motor disorders are frequent; (iii) in children, the course of dystonia may be influenced by ongoing brain maturation and by the remarkable plasticity of the young brain; (iv) drug tolerability and effectiveness can be different in children; (v) the therapeutic strategy must be discussed with both the patient and his or her parents; and (vi) the child's education must be taken into account. Based on a systematic review of the literature through June 2011 and on our personal experience, we propose a therapeutic approach to childhood dystonia. After a detailed clinical evaluation and a comprehensive work-up to rule out a treatable cause of dystonia, symptomatic treatment may include various drugs, local botulinum toxin injections, and deep brain stimulation, in addition to rehabilitation.
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Distonia/terapia , Distúrbios Distônicos/terapia , Criança , HumanosRESUMO
INTRODUCTION: Hemiplegic (or spastic unilateral) cerebral palsy accounts for about 30% of all cases of cerebral palsy. With a population prevalence of 0.6 per 1000 live births, it is the most common type of cerebral palsy among term-born children and the second most common type after diplegia among preterm infants. STATE OF THE ART: Many types of prenatal and perinatal brain injury can lead to congenital hemiplegia and brain MRI is the most useful tool to classify them with accuracy and to provide early prognostic information. Perinatal arterial ischemic stroke thus appears as the leading cause in term infants, whereas encephalopathy of prematurity is the most common cause in premature babies. Other causes include brain malformations, neonatal sinovenous thrombosis, parenchymal hemorrhage (for example due to coagulopathy or alloimmune thrombocytopenia) and the more recently described familial forms of porencephaly associated with mutations in the COL4A1 gene. PERSPECTIVES: In adjunction with pharmacologic treatment (botulinium neurotoxin injection), new evidence-based rehabilitational interventions, such as constraint-induced movement therapy and mirror therapy, are increasingly being used.
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Paralisia Cerebral , Hemiplegia , Algoritmos , Toxinas Botulínicas Tipo A/uso terapêutico , Encéfalo/anormalidades , Paralisia Cerebral/diagnóstico , Paralisia Cerebral/epidemiologia , Paralisia Cerebral/reabilitação , Terapia por Exercício , Doenças Fetais , Hemiplegia/diagnóstico , Hemiplegia/epidemiologia , Hemiplegia/reabilitação , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/epidemiologia , Espasticidade Muscular/etiologia , Modalidades de Fisioterapia , Prevalência , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/embriologiaRESUMO
Dystonias are clinically and genetically heterogeneous neurological disorders that affect movement, and are the focus of much investigative work. The recent identification of mutations in the gene THAP1 in DYT6 dystonia reopens the very interesting question of the in fine involvement of dopamine in the different types of dystonia. In this review, we will go through the recent literature in order to evaluate the many contributions to this theory as well as to highlight the difficulties in identifying a global regulatory pathway for the different forms of this disease that we are just starting to decipher.
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Dopamina/fisiologia , Distonia Muscular Deformante/genética , Proteínas Reguladoras de Apoptose/genética , Proteínas de Ligação a DNA/genética , Distonia Muscular Deformante/fisiopatologia , Heterogeneidade Genética , Humanos , Chaperonas Moleculares/genética , Mutação/fisiologia , Proteínas Nucleares/genéticaRESUMO
The CDKL5 gene has been implicated in the molecular etiology of early-onset intractable seizures with infantile spasms (IS), severe hypotonia and atypical Rett syndrome (RTT) features. So far, 48 deleterious alleles have been reported in the literature. We screened the CDKL5 gene in a cohort of 177 patients with early-onset seizures, including 30 men and 10 girls with Aicardi syndrome. The screening was negative for all men as well as for women with Aicardi syndrome, excluding the CDKL5 gene as a candidate for this neurodevelopmental disorder. We report 11 additional de novo mutations in CDKL5 in female patients. For the first time, the MLPA approach allowed the identification of a partial deletion encompassing the promoter and the first two exons of CDKL5. The 10-point mutations consist of five missenses (with recurrent amino acid changes at p.Ala40 and p.Arg178), four splicing variants and a 1-base pair duplication. We present a review of all mutated alleles published in the literature. In our study, the overall frequency of mutations in CDKL5 in women with early-onset seizures is around 8.6%, a result comparable with previous reports. Noteworthy, the CDKL5 mutation rate is high (28%) in women with early-onset seizures and IS.
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Predisposição Genética para Doença/genética , Mutação/genética , Fenótipo , Proteínas Serina-Treonina Quinases/genética , Síndrome de Rett/genética , Convulsões/genética , Western Blotting , Células Cultivadas , Pré-Escolar , Primers do DNA/genética , Feminino , Citometria de Fluxo , França , Frequência do Gene , Testes Genéticos , Humanos , Lactente , Recém-Nascido , Linhagem , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
OBJECTIVE: We have recently shown that de novo mutations in the TUBA1A gene are responsible for a wide spectrum of neuronal migration disorders. To better define the range of these abnormalities, we searched for additional mutations in a cohort of 100 patients with lissencephaly spectrum for whom no mutation was identified in DCX, LIS1 and ARX genes and compared these data to five previously described patients with TUBA1A mutations. RESULTS: We detected de novo TUBA1A mutations in six patients and highlight the existence of a prominent form of TUBA1A related lissencephaly. In four patients, the mutations identified, c.1190T>C (p.L397P), c.1265G>A (p.R422H), c.1264C>T (p.R422C), c.1306G>T (p.G436R), have not been reported before and in two others, the mutation corresponds to a recurrent missense mutation, c.790C>T (p.R264C), likely to be a hot spot of mutation. All together, it emerges that the TUBA1A related lissencephaly spectrum ranges from perisylvian pachygyria, in the less severe form, to posteriorly predominant pachygyria in the most severe, associated with dysgenesis of the anterior limb of the internal capsule and mild to severe cerebellar hypoplasia. When compared with a large series of lissencephaly of other origins (ILS17, ILSX or unknown origin), these features appear to be specific to TUBA1A related lissencephaly. In addition, TUBA1A mutated patients share a common clinical phenotype that consists of congenital microcephaly, mental retardation and diplegia/tetraplegia. CONCLUSIONS: Our data highlight the presence of consistent and specific abnormalities that should allow the differentiation of TUBA1A related lissencephalies from those related to LIS1, DCX and ARX genes.
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Lisencefalia/genética , Tubulina (Proteína)/genética , Criança , Pré-Escolar , Feminino , Heterozigoto , Humanos , Lactente , Lisencefalia/patologia , Imageamento por Ressonância Magnética , Masculino , Mutação de Sentido Incorreto , Fenótipo , Tubulina (Proteína)/químicaRESUMO
INTRODUCTION: Paroxysmal kinesigenic dyskinesia (PKD) is characterized by brief episodes of dystonia and choreoathetosis triggered by sudden voluntary movements. Disease onset is seen in the first or second decade. The attacks typically last less than one minute. Three autosomal dominant PKD loci are identified: EKD1, EKD2 and EKD3. EKD1 has an overlap with the locus of the "Infantile Convulsion and Choreoathetosis (ICCA) syndrome". The favorable natural history, the episodic nature of the symptoms and their sensitivity to anticonvulsant therapy suggest channelopathy as a mechanism of PKD. PATIENTS AND METHODS: We reviewed the clinical features, the family history, the treatment response, the evolution and the technical investigations in 19 affected individuals. RESULTS: All cases were idiopathic. Ten patients had a positive familial history. Three patients suffered from ICCA syndrome. Some atypical features were seen, such as the association of kinesigenic and nonkinesigenic attacks and the presence of migraine, ataxia, seizures and myoclonus. Acetazolamide responsiveness was seen in two patients. CONCLUSION: The coexistence of PKD and nonkinesigenic dyskinesia in several patients confirms the earlier described presence of intermediary forms, nonrepresented in the current classification of paroxysmal dyskinesias. Our study results suggest channel dysfunction and basal ganglia involvement in the pathophysiology of PKD.
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Canalopatias/fisiopatologia , Coreia/fisiopatologia , Adolescente , Adulto , Idade de Início , Aminas/uso terapêutico , Anticonvulsivantes/uso terapêutico , Canalopatias/tratamento farmacológico , Canalopatias/genética , Criança , Pré-Escolar , Coreia/tratamento farmacológico , Coreia/genética , Mapeamento Cromossômico , Ácidos Cicloexanocarboxílicos/uso terapêutico , Feminino , Gabapentina , Humanos , Lactente , Masculino , Transtornos dos Movimentos/tratamento farmacológico , Transtornos dos Movimentos/genética , Transtornos dos Movimentos/fisiopatologia , Convulsões/genética , Convulsões/psicologia , Razão de Masculinidade , Adulto Jovem , Ácido gama-Aminobutírico/uso terapêuticoRESUMO
Early onset torsion dystonia are rare movement disorders. Molecular defect is known for only a subgroup, consisting of a unique and recurrent mutation in the TOR1A gene. We undertook a nationwide census of French TOR1A-mutation carriers and the assessment of clinical associated signs. Overall, 53 index cases and 104 relatives were studied and haplotypes linked to the mutation constructed. The previously reported Ashkenazi-Jewish haplotype was found in 11 families with the remainder carrying distinct haplotypes suggesting independent mutation events. This study demonstrates the scarcity of this disease in France with estimated disease frequency of 0.13:100,000 and mutation frequency of 0.17:100,000.
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Distonia Muscular Deformante/genética , Chaperonas Moleculares/genética , Deleção de Sequência , Adolescente , Idade de Início , Estudos de Casos e Controles , Criança , Feminino , França , Frequência do Gene , Ligação Genética , Haplótipos , Heterozigoto , Humanos , Judeus/genética , Masculino , FenótipoRESUMO
OBJECTIVE: Ketogenic diet is the first line therapy for neurological symptoms associated with pyruvate dehydrogenase deficiency (PDHD) and intractable seizures in a number of disorders, including GLUT1 deficiency syndrome (GLUT1-DS). Because high-fat diet raises serious compliance issues, we investigated if oral L,D-3-hydroxybutyrate administration could be as effective as ketogenic diet in PDHD and GLUT1-DS. METHODS: We designed a partial or total progressive substitution of KD with L,D-3-hydroxybutyrate in three GLUT1-DS and two PDHD patients. RESULTS: In GLUT1-DS patients, we observed clinical deterioration including increased frequency of seizures and myoclonus. In parallel, ketone bodies in CSF decreased after introducing 3-hydroxybutyrate. By contrast, two patients with PDHD showed clinical improvement as dystonic crises and fatigability decreased under basal metabolic conditions. In one of the two PDHD children, 3-hydroxybutyrate has largely replaced the ketogenic diet, with the latter that is mostly resumed only during febrile illness. Positive direct effects on energy metabolism in PDHD patients were suggested by negative correlation between ketonemia and lactatemia (r 2 = 0.59). Moreover, in cultured PDHc-deficient fibroblasts, the increase of CO2 production after 14C-labeled 3-hydroxybutyrate supplementation was consistent with improved Krebs cycle activity. However, except in one patient, ketonemia tended to be lower with 3-hydroxybutyrate administration compared to ketogenic diet. CONCLUSION: 3-hydroxybutyrate may be an adjuvant treatment to ketogenic diet in PDHD but not in GLUT1-DS under basal metabolic conditions. Nevertheless, ketogenic diet is still necessary in PDHD patients during febrile illness.
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Paroxysmal movement disorders are not uncommon in childhood, but are probably under-recognised. Paroxysmal movement disorders are a distinctive group of disorders that represents various clinical situations, characterised by intermittent and episodic disturbances of movement. Diagnosis relies on semiological analysis, mainly based on parental description of the manifestations; video recording (during an EEG-video monitoring or home made video) are often helpful to establish the correct diagnosis. In the large majority of the cases, paroxysmal movement disorders are benign situations. Some of them are transient, as they spontaneously stop over time (benign torticolis of infancy, paroxysmal tonic upgaze). Being familiar with these disorders will lead to accurate diagnosis, so avoiding useless investigations. Most of the time, no treatment will be required, and the families will be informed of the good prognosis.
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Transtornos dos Movimentos/fisiopatologia , Criança , Diagnóstico Diferencial , Eletroencefalografia , Epilepsia , Humanos , Monitorização Fisiológica , Transtornos dos Movimentos/classificação , Transtornos dos Movimentos/etiologia , Remissão EspontâneaRESUMO
Bilateral facial nerve palsy is a rare and sometimes difficult diagnosis. We describe a case of bilateral simultaneous facial nerve palsy associated with Epstein-Barr virus (EBV) infection in a 3-year-old boy. Several symptoms led to the diagnosis of EBV infection: the clinical situation (fever, stomachache, and throat infection), white blood cell count (5300/mm3 with 70% lymphocyte count), seroconversion with EBV-specific antibodies, lymphocytic meningitis, and a positive blood EBV polymerase chain reaction (9.3×103 copies of EBV-DNA). An MRI brain scan showed bilateral gadolinium enhancement of the facial nerve. A treatment plan with IV antibiotics (ceftriaxone) and corticosteroids was implemented. Antibiotics were stopped after the diagnosis of Lyme disease was ruled out. The patient's facial weakness improved within a few weeks. Bilateral facial nerve palsy is rare and, unlike unilateral facial palsy, it is idiopathic in only 20% of cases. Therefore, it requires further investigation and examination to search for the underlying etiology. Lyme disease is the first infectious disease that should be considered in children, especially in endemic areas. An antibiotic treatment effective against Borrelia burgdorferi should be set up until the diagnosis is negated or confirmed. Further examination should include a blood test (such as immunologic testing, and serologic testing for viruses and bacterium with neurological tropism), a cerebrospinal fluid test, and an MRI brain scan to exclude any serious or curable underlying etiology. Facial bilateral nerve palsy associated with EBV is rarely described in children. Neurological complications have been reported in 7% of all EBV infections. The facial nerve is the most frequently affected of all cranial nerves. Facial palsy described in EBV infections is bilateral in 35% of all cases. The physiopathology is currently unknown. Prognosis is good most of the time.
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Infecções por Vírus Epstein-Barr/complicações , Paralisia Facial/virologia , Anticorpos Antivirais/sangue , Pré-Escolar , DNA Viral/sangue , Infecções por Vírus Epstein-Barr/diagnóstico , Herpesvirus Humano 4/genética , Humanos , MasculinoRESUMO
Aromatic L-amino acid decarboxylase (AADC) deficiency is an autosomal recessive inborn error of metabolism, affecting catecholamines and serotonin biosynthesis. Cardinal signs consist in psychomotor delay, hypotonia, oculogyric crises, dystonia, and extraneurological symptoms. PATIENTS AND METHODS: We present a retrospective descriptive multicentric study concerning ten French children with a biochemical and molecular confirmed diagnosis of AADC deficiency. RESULTS: Clinical presentation of most of our patients was consistent with the previous descriptions from the literature (hypotonia (nine children), autonomic signs (nine children), sleep disorders (eight children), oculogyric crises (eight children), motor disorders like hypertonia and involuntary movements (seven children)). We described however some phenotypic particularities. Two patients exhibited normal intellectual abilities (patients already described in the literature). We also underlined the importance of digestive symptoms like diarrhea, which occurred in five among the ten patients. We report in particular two children with chronic diarrhea, complicated by severe failure to thrive. Vanillactic acid (VLA) elevation in urines of one of these two patients led to suspect the diagnosis of AADC deficiency, as in two other patients from our population. CONCLUSION: Some symptoms like chronic diarrhea were atypical and have been poorly described in the literature up to now. Diagnosis of the AADC deficiency is sometimes difficult because of the phenotypic heterogeneity of the disease and VLA elevation in urines should suggest the diagnosis.
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INTRODUCTION: Parry-Romberg's syndrome or progressive facial hemiatrophy is a rare disorder of unknown etiology which may be accompanied by neurological complications, frequently epilepsy, usually focal refractory epilepsy. The associated brain lesions are located on the same side as the half face atrophy and may progress. OBSERVATION: We report the cases of two patients with Parry-Romberg's syndrome and epilepsy. Neurosurgery was performed in one patient, enabling a histological study. CONCLUSION: The link between Parry-Romberg's syndrome and epilepsy is discussed and the neurodevelopmental theory with vascular dysgenesis is suggested.
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Epilepsia/complicações , Hemiatrofia Facial/complicações , Anticonvulsivantes/uso terapêutico , Encéfalo/patologia , Pré-Escolar , Eletroencefalografia , Epilepsia/patologia , Epilepsia/cirurgia , Hemiatrofia Facial/patologia , Hemiatrofia Facial/cirurgia , Feminino , Lateralidade Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Procedimentos Neurocirúrgicos , Tomografia Computadorizada por Raios XRESUMO
Autism is a pervasive developmental disorder characterised by an impairment in social interaction and in communication, with unusual behaviour. Genetic factors are predominent in autism pathogenesis, in contrast with the environmental factors that would modulate the phenotype. The genetic polymorphism and the phenotypic heterogeneity make the autism a complex disorder to study. Genetic research on families with multiple affected children and biochemical mechanisms studies represent the sources for identifying the susceptibility genes in autism.
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Transtorno Autístico/genética , Predisposição Genética para Doença , Criança , Humanos , Fenótipo , Polimorfismo GenéticoRESUMO
McArdle's disease (glycogenosis type V) is an inherited glycogen storage disease characterized clinically by myalgia, cramps and sometimes myoglobinuria, triggered by exercise. The onset of exercise intolerance is usually in late childhood or adolescence and diagnosis is exceptionally established during infancy. We report the case of a 6-year-old girl who had been complaining of aching muscles for a long time, and who presented after a near-drowning incident, with extensive muscle necrosis, probably secondary to myophosphorylase deficiency-induced cramps. These unusual manifestations led to the diagnosis of this rare disorder. We compare the clinical findings of this case to nine previous reports. This highlights the heterogeneous spectrum of this disease in childhood and supports the distinction of three clinical pictures in childhood: a neonatal form rapidly fatal, a milder form with congenital myopathic symptoms and a benign classical form with myalgia, cramps and pigmenturia.
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Doença de Depósito de Glicogênio Tipo V/diagnóstico , Biópsia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Cãibra Muscular/enzimologia , Músculo Esquelético/enzimologia , Músculo Esquelético/patologia , Afogamento Iminente , Necrose , Fosforilases/deficiência , Índice de Gravidade de DoençaRESUMO
Hyperprolinemia type I is a deficiency of proline oxidase (McKusick 23950), leading to hyperprolinemia and iminoglycinuria, usually with renal involvement. Hyperprolinemia type I is considered a benign trait. We reported a case of hyperprolinemia type I with a severe neurologic disorder and without renal involvement. The patient had marked psychomotor delay and right hemiparesis. Epilepsy was characterized by status epilepticus or a cluster of seizures. Laboratory findings revealed elevated levels of proline in the serum, urine, and cerebrospinal fluid without delta1-pyrroline 5-carboxylate dehydrogenase in the plasma or urine. Fluorescence in situ hybridization excluded a chromosome 22q11 deletion. Vigabatrin inhibits ornithine transaminase. Thus, vigabatrin could lead to a depletion of the normal pool of pyrroline 5-carboxylate dehydrogenase and could aggravate the clinical condition of the child. In this study, vigabatrin was discontinued. In the following months, the patient had marked psychomotor improvement, without modification of the epilepsy. We suggest that vigabatrin should be avoided in hyperprolinemia type I.
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Anticonvulsivantes/efeitos adversos , Encéfalo/patologia , Epilepsia/tratamento farmacológico , Erros Inatos do Metabolismo/diagnóstico , Prolina Oxidase/deficiência , Vigabatrina/efeitos adversos , Ventrículos Cerebrais/patologia , Epilepsia/etiologia , Humanos , Lactente , Masculino , Erros Inatos do Metabolismo/complicações , Ornitina-Oxo-Ácido Transaminase/antagonistas & inibidores , Espaço Subaracnóideo/patologiaRESUMO
Chromosome 22q11 deletion (CATCH 22 syndrome or velocardiofacial syndrome) is one of the most frequent chromosomal syndromes. Neurological features other than cognitive disorders are probably the least-described part of the expanding phenotype of the 22q11 deletion. We report the neurological features of three unrelated children with a de novo deletion: one patient with an autistic disorder, a second patient with hypocalcaemic neonatal seizures and unusual persistent epileptic focus at electroencephalographic follow-up, and a third patient with atypical absence epilepsy. These observations enlarge the clinical and neurological spectrum of the 22q11 deletion. Awareness of such cases is necessary, and a diagnosis of the 22q11 deletion should be suspected in children with common neurological features associated with severe or mild dysmorphism. Diagnosis of the 22q11 deletion should be confirmed by fluorescence in situ hybridization analysis associated with standard chromosomal analysis.