RESUMO
Epileptic encephalopathies (EEs) are severe brain disorders with excessive ictal (seizure) and interictal (electrographic epileptiform discharges) activity in developing brain which may result in progressive cognitive and neuropsychological deterioration. In contrast to regular epilepsy where the treatment goal is to prevent the seizure (ictal) recurrence, in patients with EE the goal is to treat both ictal as well as interictal activity to prevent further progression. With the introduction of genetic sequencing technologies over the past 20 years, there is growing recognition of the genetic basis of EE, with the majority due to monogenic causes. Monogenic etiologies of EE include pathogenic variants in the γ-aminobutyric acid type A receptor (GABA-A) encoding gene family. We present a 2-year-old patient with EE, hypotonia, and global developmental delays. Clinical trio exome sequencing showed a novel, de novo variant in GABRG1. GABRG1 encodes the γ1 subunit of the GABA-A receptor. To date, there has not been an association of EE with pathogenic variants in GABRG1. This variant is predicted to be damaging to protein structure and function, and the patient's phenotype is similar to those with pathogenic variants in other members of the GABA-A receptor encoding gene family.
Assuntos
Encefalopatias , Epilepsia Generalizada , Epilepsia , Humanos , Hipotonia Muscular/genética , Hipotonia Muscular/complicações , Receptores de GABA-A/genética , Epilepsia/diagnóstico , Epilepsia/genética , Epilepsia/complicações , Convulsões/complicações , Encefalopatias/genéticaRESUMO
Pathogenic de novo variants in the X-linked gene SLC35A2 encoding the major Golgi-localized UDP-galactose transporter required for proper protein and lipid glycosylation cause a rare type of congenital disorder of glycosylation known as SLC35A2-congenital disorders of glycosylation (CDG; formerly CDG-IIm). To date, 29 unique de novo variants from 32 unrelated individuals have been described in the literature. The majority of affected individuals are primarily characterized by varying degrees of neurological impairments with or without skeletal abnormalities. Surprisingly, most affected individuals do not show abnormalities in serum transferrin N-glycosylation, a common biomarker for most types of CDG. Here we present data characterizing 30 individuals and add 26 new variants, the single largest study involving SLC35A2-CDG. The great majority of these individuals had normal transferrin glycosylation. In addition, expanding the molecular and clinical spectrum of this rare disorder, we developed a robust and reliable biochemical assay to assess SLC35A2-dependent UDP-galactose transport activity in primary fibroblasts. Finally, we show that transport activity is directly correlated to the ratio of wild-type to mutant alleles in fibroblasts from affected individuals.
Assuntos
Defeitos Congênitos da Glicosilação/genética , Proteínas de Transporte de Monossacarídeos/genética , Proteínas de Transporte de Monossacarídeos/metabolismo , Uridina Difosfato Galactose/metabolismo , Animais , Biópsia , Células CHO , Células Cultivadas , Defeitos Congênitos da Glicosilação/metabolismo , Defeitos Congênitos da Glicosilação/patologia , Cricetulus , Feminino , Humanos , Masculino , MutaçãoRESUMO
OBJECTIVE: Several small case series identified KCTD7 mutations in patients with a rare autosomal recessive disorder designated progressive myoclonic epilepsy (EPM3) and neuronal ceroid lipofuscinosis (CLN14). Despite the name KCTD (potassium channel tetramerization domain), KCTD protein family members lack predicted channel domains. We sought to translate insight gained from yeast studies to uncover disease mechanisms associated with deficiencies in KCTD7 of unknown function. METHODS: Novel KCTD7 variants in new and published patients were assessed for disease causality using genetic analyses, cell-based functional assays of patient fibroblasts and knockout yeast, and electron microscopy of patient samples. RESULTS: Patients with KCTD7 mutations can exhibit movement disorders or developmental regression before seizure onset, and are distinguished from similar disorders by an earlier age of onset. Although most published KCTD7 patient variants were excluded from a genome sequence database of normal human variations, most newly identified patient variants are present in this database, potentially challenging disease causality. However, genetic analysis and impaired biochemical interactions with cullin 3 support a causal role for patient KCTD7 variants, suggesting deleterious alleles of KCTD7 and other rare disease variants may be underestimated. Both patient-derived fibroblasts and yeast lacking Whi2 with sequence similarity to KCTD7 have impaired autophagy consistent with brain pathology. INTERPRETATION: Biallelic KCTD7 mutations define a neurodegenerative disorder with lipofuscin and lipid droplet accumulation but without defining features of neuronal ceroid lipofuscinosis or lysosomal storage disorders. KCTD7 deficiency appears to cause an underlying autophagy-lysosome defect conserved in yeast, thereby assigning a biological role for KCTD7. Ann Neurol 2018;84:774-788.
Assuntos
Autofagia/genética , Lisossomos/genética , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/patologia , Canais de Potássio/deficiência , Idade de Início , Pré-Escolar , Feminino , Humanos , Lactente , Lisossomos/patologia , Masculino , Mutação , Linhagem , Canais de Potássio/genética , Proteínas de Saccharomyces cerevisiae/genéticaRESUMO
Neuropathology of resected brain tissue has revealed an association of focal cortical dysplasia (FCD) with drug-resistant epilepsy (DRE). Recent studies have shown that the mechanistic target of rapamycin (mTOR) pathway is hyperactivated in FCD as evidenced by increased phosphorylation of the ribosomal protein S6 (S6) at serine 240/244 (S(240/244) ), a downstream target of mTOR. Moreover, extracellular regulated kinase (ERK) has been shown to phosphorylate S6 at serine 235/236 (S(235/236) ) and tuberous sclerosis complex 2 (TSC2) at serine 664 (S(664) ) leading to hyperactive mTOR signaling. We evaluated ERK phosphorylation of S6 and TSC2 in two types of FCD (FCD I and FCD II) as a candidate mechanism contributing to mTOR pathway dysregulation. Tissue samples from patients with tuberous sclerosis (TS) served as a positive control. Immunostaining for phospho-S6 (pS6(240/244) and pS6(235/236) ), phospho-ERK (pERK), and phospho-TSC2 (pTSC2) was performed on resected brain tissue with FCD and TS. We found increased pS6(240/244) and pS6(235/236) staining in FCD I, FCD II and TS compared to normal-appearing tissue, while pERK and pTSC2 staining was increased only in FCD IIb and TS tissue. Our results suggest that both the ERK and mTOR pathways are dysregulated in FCD and TS; however, the signaling alterations are different for FCD I as compared to FCD II and TS.
Assuntos
Epilepsia/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Malformações do Desenvolvimento Cortical do Grupo I/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Adolescente , Criança , Pré-Escolar , Ativação Enzimática , Epilepsia/patologia , Feminino , Humanos , Imuno-Histoquímica , Lactente , Sistema de Sinalização das MAP Quinases/fisiologia , Imageamento por Ressonância Magnética , Masculino , Malformações do Desenvolvimento Cortical do Grupo I/patologia , Fosforilação , Proteína S6 Ribossômica/metabolismo , Proteína 2 do Complexo Esclerose Tuberosa , Proteínas Supressoras de Tumor/metabolismoRESUMO
OBJECTIVE: To describe the time elapsed from onset of pediatric convulsive status epilepticus (SE) to administration of antiepileptic drug (AED). METHODS: This was a prospective observational cohort study performed from June 2011 to June 2013. Pediatric patients (1 month-21 years) with convulsive SE were enrolled. In order to study timing of AED administration during all stages of SE, we restricted our study population to patients who failed 2 or more AED classes or needed continuous infusions to terminate convulsive SE. RESULTS: We enrolled 81 patients (44 male) with a median age of 3.6 years. The first, second, and third AED doses were administered at a median (p25-p75) time of 28 (6-67) minutes, 40 (20-85) minutes, and 59 (30-120) minutes after SE onset. Considering AED classes, the initial AED was a benzodiazepine in 78 (96.3%) patients and 2 (2-3) doses of benzodiazepines were administered before switching to nonbenzodiazepine AEDs. The first and second doses of nonbenzodiazepine AEDs were administered at 69 (40-120) minutes and 120 (75-296) minutes. In the 64 patients with out-of-hospital SE onset, 40 (62.5%) patients did not receive any AED before hospital arrival. In the hospital setting, the first and second in-hospital AED doses were given at 8 (5-15) minutes and 16 (10-40) minutes after SE onset (for patients with in-hospital SE onset) or after hospital arrival (for patients with out-of-hospital SE onset). CONCLUSIONS: The time elapsed from SE onset to AED administration and escalation from one class of AED to another is delayed, both in the prehospital and in-hospital settings.
Assuntos
Anticonvulsivantes/administração & dosagem , Benzodiazepinas/administração & dosagem , Protocolos Clínicos , Estado Epiléptico/tratamento farmacológico , Criança , Pré-Escolar , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Masculino , Estudos Prospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
Mononuclear cells (MNCs) and mesenchymal stem cells (MSCs) derived from the bone marrow and other sources have received significant attention as donor cells for treating various neurological disorders due to their robust neuroprotective and anti-inflammatory effects. Moreover, it is relatively easy to procure these cells from both autogenic and allogenic sources. Currently, there is considerable interest in examining the usefulness of these cells for conditions such as status epilepticus (SE) and chronic epilepsy. A prolonged seizure activity in SE triggers neurodegeneration in the limbic brain areas, which elicits epileptogenesis and evolves into a chronic epileptic state. Because of their potential for providing neuroprotection, diminishing inflammation and curbing epileptogenesis, early intervention with MNCs or MSCs appears attractive for treating SE as such effects may restrain the development of chronic epilepsy typified by spontaneous seizures and learning and memory impairments. Delayed administration of these cells after SE may also be useful for easing spontaneous seizures and cognitive dysfunction in chronic epilepsy. This concise review evaluates the current knowledge and outlook pertaining to MNC and MSC therapies for SE and chronic epilepsy. In the first section, the behavior of these cells in animal models of SE and their efficacy to restrain neurodegeneration, inflammation, and epileptogenesis are discussed. The competence of these cells for suppressing seizures and improving cognitive function in chronic epilepsy are conferred in the next section. The final segment ponders issues that need to be addressed to pave the way for clinical application of these cells for SE and chronic epilepsy.
Assuntos
Células da Medula Óssea/metabolismo , Epilepsia/terapia , Regeneração Tecidual Guiada/métodos , Células-Tronco Mesenquimais/metabolismo , Estado Epiléptico/terapia , Animais , Doença Crônica , HumanosRESUMO
IMPORTANCE: Isolated sulfite oxidase deficiency (ISOD) causes severe intellectual disability, epilepsy, and shortened life expectancy. Intractable seizures are invariable in children with ISOD; however, to our knowledge, infantile spasms with a corresponding hypsarrhythmia pattern on electroencephalogram have never been reported. In addition, the nonepileptic paroxysmal movement disorder hyperekplexia has not previously been reported with ISOD. OBSERVATIONS: We describe an infant with ISOD who initially presented with neonatal seizures, diffusion restriction noted on magnetic resonance imaging, and elevated serum S-sulfocysteine consistent with ISOD. A homozygous mutation in the SUOX gene was identified, confirming the diagnosis. Uniquely, this patient developed a profound accentuated startle response that did not have a corresponding electrographic change on electroencephalogram consistent with hyperekplexia. This was followed by a change in the child's electroencephalogram to the chaotic pattern of hypsarrhythmia and brief tonic seizures with attenuation of the hypsarrhythmia pattern characteristic of infantile spasms. CONCLUSIONS AND RELEVANCE: The evolution of seizures associated with ISOD is poorly characterized because of the small number of patients. We report what we believe to be the first case of a child with ISOD who developed infantile spasms and hyperekplexia. This expands the phenotypes associated with ISOD and also should caution clinicians to not assume that all abnormal movements are seizures.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/genética , Mutação/genética , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/genética , Convulsões/genética , Espasmos Infantis/genética , Rigidez Muscular Espasmódica/genética , Sulfito Oxidase/deficiência , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Eletroencefalografia/métodos , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética/métodos , Masculino , Convulsões/etiologia , Espasmos Infantis/etiologia , Rigidez Muscular Espasmódica/etiologia , Sulfito Oxidase/genéticaRESUMO
PURPOSE: Status epilepticus (SE) is a life-threatening condition that can be refractory to initial treatment. Randomized controlled studies to guide treatment choices, especially beyond first-line drugs, are not available. This report summarizes the evidence that guides the management of refractory convulsive SE (RCSE) in children, defines gaps in our clinical knowledge and describes the development and works of the 'pediatric Status Epilepticus Research Group' (pSERG). METHODS: A literature review was performed to evaluate current gaps in the pediatric SE and RCSE literature. In person and online meetings helped to develop and expand the pSERG network. RESULTS: The care of pediatric RCSE is largely based on extrapolations of limited evidence derived from adult literature and supplemented with case reports and case series in children. No comparative effectiveness trials have been performed in the pediatric population. Gaps in knowledge include risk factors for SE, biomarkers of SE and RCSE, second- and third-line treatment options, and long-term outcome. CONCLUSION: The care of children with RCSE is based on limited evidence. In order to address these knowledge gaps, the multicenter pSERG was established to facilitate prospective collection, analysis, and sharing of de-identified data and biological specimens from children with RCSE. These data will allow identification of treatment strategies associated with better outcomes and delineate evidence-based interventions to improve the care of children with SE.
Assuntos
Estado Epiléptico/terapia , Anticonvulsivantes/uso terapêutico , Benzodiazepinas/uso terapêutico , Criança , Medicina Baseada em Evidências , Humanos , Estudos Multicêntricos como Assunto , Projetos de Pesquisa , Estado Epiléptico/epidemiologia , Estado Epiléptico/fisiopatologiaRESUMO
OBJECTIVE: Higher benchmarks in safety for patients undergoing neurosurgery have been introduced. With these principles, new tools and techniques were established, including intraoperative neurophysiological monitoring (IONM). Current trends as a function of patient-, surgeon-, and procedure-related factors and complication rates in the utilization of IONM as an adjunct to the practice of pediatric neurosurgery have not been investigated previously. METHODS: Between 2008 and 2011, 4467 neurosurgical procedures were performed on 2352 patients at Texas Children's Hospital. A retrospective chart review was performed in which surgeon, procedure, and patient characteristics, as well as perioperative complications, were recorded for IONM and non-IONM cases. RESULTS: Neurosurgical procedures performed with IONM steadily increased. Surgeon-related factors associated with IONM use included surgeons with <10 years of practice (P < .0001), and subspecialty interest in spine (P < .0001) and oncology (P = .0048). Procedure-related factors associated with IONM use included operations involving the spinal cord (P < .0001). Patient-related factors associated with IONM use included children older than 3 years of age and with increased American Society of Anesthesiologists score (P < .0001). The neurological complication rate in the IONM cohort (range 3.4% to 11.3%; mean 6.4%) was significantly higher compared to the non-IONM cohort (range 1.1% to 1.8%; mean 1.5%) (P < .0001). CONCLUSIONS: The percent of procedures performed with IONM increased. However, these trends do not seem governed by improvement to patient outcomes because the complication rates were higher in the IONM cohort than the non-IONM cohort.
Assuntos
Doenças do Sistema Nervoso Central/cirurgia , Potencial Evocado Motor , Monitorização Neurofisiológica Intraoperatória/estatística & dados numéricos , Procedimentos Neurocirúrgicos/métodos , Complicações Pós-Operatórias/epidemiologia , Prática Profissional/estatística & dados numéricos , Adolescente , Adulto , Benchmarking , Criança , Pré-Escolar , Humanos , Lactente , Monitorização Neurofisiológica Intraoperatória/normas , Procedimentos Neurocirúrgicos/normas , Pediatria , Prática Profissional/normas , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Untreated epileptic encephalopathies in children may potentially have disastrous outcomes. Treatment with antiepileptic drugs (AEDs) often may not control the seizures, and even if they do, this measure is only symptomatic and not specific. It is especially valuable to identify potential underlying conditions that have specific treatments. Only a few conditions have definitive treatments that can potentially modify the natural course of disease. In this paper, we discuss the few such conditions that are responsive to vitamin or vitamin derivatives.
RESUMO
We delineated and analyzed directly oriented paralogous low-copy repeats (DP-LCRs) in the most recent version of the human haploid reference genome. The computationally defined DP-LCRs were cross-referenced with our chromosomal microarray analysis (CMA) database of 25,144 patients subjected to genome-wide assays. This computationally guided approach to the empirically derived large data set allowed us to investigate genomic rearrangement relative frequencies and identify new loci for recurrent nonallelic homologous recombination (NAHR)-mediated copy-number variants (CNVs). The most commonly observed recurrent CNVs were NPHP1 duplications (233), CHRNA7 duplications (175), and 22q11.21 deletions (DiGeorge/velocardiofacial syndrome, 166). In the â¼25% of CMA cases for which parental studies were available, we identified 190 de novo recurrent CNVs. In this group, the most frequently observed events were deletions of 22q11.21 (48), 16p11.2 (autism, 34), and 7q11.23 (Williams-Beuren syndrome, 11). Several features of DP-LCRs, including length, distance between NAHR substrate elements, DNA sequence identity (fraction matching), GC content, and concentration of the homologous recombination (HR) hot spot motif 5'-CCNCCNTNNCCNC-3', correlate with the frequencies of the recurrent CNVs events. Four novel adjacent DP-LCR-flanked and NAHR-prone regions, involving 2q12.2q13, were elucidated in association with novel genomic disorders. Our study quantitates genome architectural features responsible for NAHR-mediated genomic instability and further elucidates the role of NAHR in human disease.
Assuntos
Alelos , Transtornos Cromossômicos/genética , Variações do Número de Cópias de DNA , Doenças Genéticas Inatas/genética , Recombinação Homóloga , Proteínas Adaptadoras de Transdução de Sinal/genética , Composição de Bases , Deleção Cromossômica , Duplicação Cromossômica , Proteínas do Citoesqueleto , Genoma Humano , Humanos , Proteínas de Membrana/genética , Motivos de Nucleotídeos , Receptor Nicotínico de Acetilcolina alfa7/genéticaRESUMO
BACKGROUND: Invasive monitoring using subdural electrodes is often valuable for characterizing the anatomic source of seizures in intractable epilepsy. Covering the interhemispheric surface with subdural electrodes represents a particular challenge, with a potentially higher risk of complications than covering the dorsolateral cortex. OBJECTIVE: To better understand the safety and utility of interhemispheric subdural electrodes (IHSE). METHODS: We retrospectively reviewed the charts of 24 patients who underwent implantation of IHSE by a single neurosurgeon from 2003 to 2010. Generous midline exposure, meticulous preservation of veins, and sharp microdissection were used to facilitate safe interhemispheric grid placement under direct visualization. RESULTS: The number of IHSE contacts implanted ranged from 10 to 106 (mean = 39.8) per patient. Monitoring lasted for 5.5 days on average (range, 2-24 days), with an adequate sample of seizures captured in all patients before explantation, and with a low complication rate similar to that reported for grid implantation of the dorsolateral cortex. One patient (of 24) experienced symptomatic mass effect. No other complications clearly related to grid implantation and monitoring, such as clinically evident neurological deficits, infection, hematoma, or infarction, were noted. Among patients implanted with IHSE, monitoring led to a paramedian cortical resection in 67%, a resection in a region not covered by IHSE in 17%, and explantation without resection in 17%. CONCLUSION: When clinical factors suggest the possibility of an epileptic focus at or near the midline, invasive monitoring of the paramedian cortex with interhemispheric grids can be safely used to define the epileptogenic zone and map local cortical function.
Assuntos
Eletrodos Implantados , Epilepsia/cirurgia , Microcirurgia/métodos , Monitorização Fisiológica/métodos , Espaço Subdural/cirurgia , Adolescente , Adulto , Córtex Cerebral/fisiologia , Córtex Cerebral/cirurgia , Criança , Pré-Escolar , Eletroencefalografia , Epilepsia/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/efeitos adversos , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: Neurophysiological monitoring during complex spine procedures may reduce risk of injury by providing feedback to the operating surgeon. This tool is a well-established and important surgical adjunct in adults, but clinical data in children are not well described. Moreover, to the best of our knowledge, neurophysiologic intraoperative monitoring data have not been reported in children with neurodevelopmental disorders, such as Down syndrome, who commonly present with craniocervical instability requiring internal fixation. The purpose of this study is to determine the reliability and safety of neurophysiologic intraoperative monitoring in a group of children with Down syndrome undergoing neurosurgical spine procedures. METHODS: A total of six consecutive spinal procedures in six children with Down syndrome (three boys and three girls; mean age 10 years, range 4-16 years) were analyzed between January 1, 2008 and June 31, 2011. Somatosensory evoked potentials were stimulated at the ulnar nerve and tibial nerve for upper and lower extremities, respectively, and recorded at Erb's point and the scalp. Motor evoked potentials were elicited by transcranial electrical stimulation and recorded at the extensor carpi ulnaris muscle and tibialis anterior muscle for upper and lower extremities, respectively. A standardized anesthesia protocol for monitoring consisted of a titrated propofol drip combined with bolus dosing of fentanyl or sufentanil. RESULTS: Somatosensory and motor evoked potentials were documented at the beginning and end of the procedure in all six patients. Changes during the surgery were recorded. Five patients maintained somatosensory potentials throughout surgery. One patient demonstrated a >10% increase in latency or >50% decrease in amplitude suggesting spinal cord dysfunction. A mean baseline stimulation threshold for motor evoked potentials of 485 + 85 V (range 387-600 V) was used. Four patients maintained motor evoked potentials throughout surgery. One patient had loss of left lower somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) after rod placement; upon removal of the rod, SSEPs returned but not MEPs. Another patient did not have consistent MEPs on one side and had absent MEPs on the contralateral side throughout the case. Loss of MEPs in these two patients did not correlate with postoperative neurological status. There were no complications directly related to neurophysiologic intraoperative monitoring technique. CONCLUSIONS: Neurophysiologic intraoperative monitoring during neurosurgical procedures in children with Down syndrome may be reliably and safely implemented. Changes in neurophysiologic parameters during surgery must be carefully interpreted, and discussed with the neurosurgeon, neurophysiologist, and neuroanesthesiologist, and may not correlate with postoperative clinical changes. These changes may be related to abnormal physiology rather than an insult at the time of surgery. Nonetheless, the authors advocate routine neurophysiologic intraoperative monitoring in this special group of children undergoing neurosurgical spine procedures.
Assuntos
Síndrome de Down/fisiopatologia , Síndrome de Down/cirurgia , Potencial Evocado Motor/fisiologia , Potenciais Somatossensoriais Evocados/fisiologia , Monitorização Intraoperatória/métodos , Adolescente , Criança , Pré-Escolar , Síndrome de Down/diagnóstico , Feminino , Humanos , MasculinoRESUMO
Untreated maple syrup urine disease (MSUD) leads to encephalopathy in neonates and causes abnormalities on the electroencephalogram (EEG). A case is presented of MSUD with unique features consisting of a comb-like rhythm before the therapy and its disappearance with therapy is presented. This case illustrates the potential use of the EEG in the identification of this specific cause of a neonatal encephalopathy.
Assuntos
Relógios Biológicos , Encéfalo/fisiopatologia , Doença da Urina de Xarope de Bordo/diagnóstico , Doença da Urina de Xarope de Bordo/fisiopatologia , Humanos , Recém-Nascido , MasculinoAssuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/classificação , Epilepsia/tratamento farmacológico , Adolescente , Adulto , Fatores Etários , Anticonvulsivantes/economia , Criança , Transtornos Cognitivos/economia , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/prevenção & controle , Resistência a Múltiplos Medicamentos , Epilepsia/economia , Epilepsia/cirurgia , Custos de Cuidados de Saúde , Humanos , Prognóstico , Encaminhamento e ConsultaRESUMO
OBJECTIVES: Limb girdle muscular dystrophy (LGMD) is a diverse group of myopathic disorders characterized by proximal muscle weakness and hyperCKemia. Mutations encoding sarcoglycans and numerous other proteins have been shown to be responsible for most cases. We report a series of girls with a negative family history for boys with Duchenne muscular dystrophy, demonstrating an LGMD phenotype associated with dystrophinopathy. METHODS: A retrospective chart review of all girls presenting with the LGMD phenotype to our clinic between January 2001 and September 2007 was conducted. Patients 18 years old or younger with dystrophinopathy proven by muscle biopsy and/or gene mutations and a negative family history for affected boys were included in the review. RESULTS: Five patients, 4 to 10 years of age at presentation, were included in the series. Four had an LGMD phenotype at presentation. All five patients had hyperCKemia, all five patients had gene mutations, and four patients had muscle biopsy consistent with dystrophinopathy. CONCLUSION: Dystrophinopathy is an important cause of LGMD phenotype in girls and should be considered in the differential diagnosis.
Assuntos
Distrofina/genética , Distrofia Muscular do Cíngulo dos Membros/genética , Distrofia Muscular do Cíngulo dos Membros/patologia , Mutação/genética , Fenótipo , Criança , Pré-Escolar , Análise Mutacional de DNA/métodos , Éxons/genética , Feminino , Genótipo , Humanos , Músculo Esquelético/patologia , Distrofia Muscular do Cíngulo dos Membros/fisiopatologia , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Estudos RetrospectivosRESUMO
Hypertrophy of the optic nerves and optic chiasm is described in a 5-month-old boy with infantile Krabbe disease. Optic nerve and optic chiasm hypertrophy is a rarely described feature of Krabbe disease. The areas of the prechiasmatic optic nerves and optic chiasm were measured and compared with those of 26 age-matched controls. The areas of the prechiasmatic optic nerves and optic chiasm were 132% and 53% greater than normal, respectively.