ABSTRACT
An ongoing challenge in children presenting with motor delay/impairment early in life is to identify neurogenetic disorders with a clinical phenotype, which can be misdiagnosed as cerebral palsy (CP). To help distinguish patients in these two groups, conventional magnetic resonance imaging of the brain has been of great benefit in "unmasking" many of these genetic etiologies and has provided important clues to differential diagnosis in others. Recent advances in molecular genetics such as chromosomal microarray and next-generation sequencing have further revolutionized the understanding of etiology by more precisely classifying these disorders with a molecular cause. In this paper, we present a review of neurogenetic disorders masquerading as cerebral palsy evaluated at one institution. We have included representative case examples children presenting with dyskinetic, spastic, and ataxic phenotypes, with the intent to highlight the time-honored approach of using clinical tools of history and examination to focus the subsequent etiologic search with advanced neuroimaging modalities and molecular genetic tools. A precise diagnosis of these masqueraders and their differentiation from CP is important in terms of therapy, prognosis, and family counseling. In summary, this review serves as a continued call to remain vigilant for current and other to-be-discovered neurogenetic masqueraders of cerebral palsy, thereby optimizing care for patients and their families.
Subject(s)
Cerebral Palsy/diagnosis , Developmental Disabilities/diagnosis , Diagnostic Errors , Genetic Diseases, Inborn/diagnosis , Molecular Diagnostic Techniques , Nervous System Diseases/diagnosis , Adult , Asphyxia Neonatorum/diagnosis , Asphyxia Neonatorum/genetics , Birth Injuries/diagnosis , Birth Injuries/genetics , Brain/embryology , Brain Diseases, Metabolic/diagnosis , Brain Diseases, Metabolic/genetics , Cell Movement , Cerebral Palsy/genetics , Child , Child, Preschool , Chromosome Disorders/diagnosis , Chromosome Disorders/genetics , Developmental Disabilities/genetics , Diagnosis, Differential , Exome , Female , Genetic Diseases, Inborn/genetics , Genome-Wide Association Study , Genomics , Globus Pallidus/pathology , Humans , Hypoxia, Brain/diagnosis , Hypoxia, Brain/genetics , Infant, Newborn , Leukoencephalopathies/diagnosis , Leukoencephalopathies/genetics , Leukoencephalopathies/metabolism , Lysosomal Storage Diseases, Nervous System/diagnosis , Lysosomal Storage Diseases, Nervous System/genetics , Male , Mitochondrial Diseases/diagnosis , Mitochondrial Diseases/genetics , Movement Disorders/diagnosis , Movement Disorders/genetics , Muscle Spasticity/diagnosis , Muscle Spasticity/genetics , Nervous System Diseases/genetics , Neurotransmitter Agents/metabolism , Stroke/congenital , Stroke/diagnosis , Tissue Array AnalysisABSTRACT
Schizophrenia and autism are two poorly understood clinical syndromes that differ in age of onset and clinical profile. However, recent genetic and epidemiological research suggests that these two neurodevelopmental disorders share certain risk factors. The aims of this review are to describe modifiable risk factors that have been identified in both disorders, and, where available, collate salient systematic reviews and meta-analyses that have examined shared risk factors. Based on searches of Medline, Embase and PsycINFO, inspection of review articles and expert opinion, we first compiled a set of candidate modifiable risk factors associated with autism. Where available, we next collated systematic-reviews (with or without meta-analyses) related to modifiable risk factors associated with both autism and schizophrenia. We identified three modifiable risk factors that have been examined in systematic reviews for both autism and schizophrenia. Advanced paternal age was reported as a risk factor for schizophrenia in a single meta-analysis and as a risk factor in two meta-analyses for autism. With respect to pregnancy and birth complications, for autism one meta-analysis identified maternal diabetes and bleeding during pregnancy as risks factors for autism whilst a meta-analysis of eight studies identified obstetric complications as a risk factor for schizophrenia. Migrant status was identified as a risk factor for both autism and schizophrenia. Two separate meta-analyses were identified for each disorder. Despite distinct clinical phenotypes, the evidence suggests that at least some non-genetic risk factors are shared between these two syndromes. In particular, exposure to drugs, nutritional excesses or deficiencies and infectious agents lend themselves to public health interventions. Studies are now needed to quantify any increase in risk of either autism or schizophrenia that is associated with these modifiable environmental factors.
Subject(s)
Autistic Disorder/epidemiology , Brain/growth & development , Pregnancy Complications/epidemiology , Schizophrenia/epidemiology , Animals , Autistic Disorder/diagnosis , Autistic Disorder/genetics , Birth Injuries/diagnosis , Birth Injuries/epidemiology , Birth Injuries/genetics , Brain/embryology , Female , Humans , Meta-Analysis as Topic , Pregnancy , Pregnancy Complications/diagnosis , Pregnancy Complications/genetics , Risk Factors , Schizophrenia/diagnosis , Schizophrenia/geneticsABSTRACT
INTRODUCTION AND HYPOTHESIS: This study aims to investigate the effects of simulated birth trauma and ovariectomy on detrusor muscarinic receptors (M2 and M3), urethral neuronal nitric oxide synthase (nNOS), and estrogen receptor beta (ER beta). METHODS: Forty primiparous rats were equally divided into five groups: group A--delivery, group B--delivery plus ovariectomy, group C--delivery plus balloon dilatation for 2 h, group D--delivery plus balloon dilatation for 4 h, and group E--delivery plus balloon dilatation for 2 h plus ovariectomy. The gene expression of M2, M3, nNOS, and ER beta were assessed by reverse transcription polymerase chain reaction. RESULTS: Significant decreases in mRNA expression of M2 receptors and nNOS (P < 0.05), and a significant increase in M3 mRNA expression (P < 0.05) were observed in groups D and E when compared with group A. CONCLUSIONS: Ovariectomy following birth trauma may synergistically impact the function of urinary tract, this being possibly related to the modification of the gene expression of muscarinic receptors.
Subject(s)
Birth Injuries/genetics , Gene Expression , Ovariectomy , RNA, Messenger/genetics , Receptors, Muscarinic/genetics , Urinary Bladder/metabolism , Animals , Birth Injuries/metabolism , Disease Models, Animal , Estrogen Receptor beta/biosynthesis , Estrogen Receptor beta/genetics , Female , Immunohistochemistry , Nitric Oxide Synthase Type I/biosynthesis , Nitric Oxide Synthase Type I/genetics , Pregnancy , Rats , Rats, Sprague-Dawley , Receptor, Muscarinic M2/biosynthesis , Receptor, Muscarinic M2/genetics , Receptor, Muscarinic M3/biosynthesis , Receptor, Muscarinic M3/genetics , Receptors, Muscarinic/biosynthesis , Reverse Transcriptase Polymerase Chain Reaction , Urethra/metabolismABSTRACT
El documento se divide en cinco etapas que son: 1.- Etapa previa al nacimiento 2.- Etapa del embarazo 3.- Etapa del parto 4.- Etapa del puerperio 5.- Etapa neonatal. Para lograr un resultado óptimo en la utilización del manual, se recomienda lo siguiente: a).- Leerlo completamente dos o tres veces, en forma individual para familiarizarse y compenetrarse con la metodología de trabajo a seguir, para cada una de las etapas b).- Tenerlo siempre disponible durante los periódos de consulta para poder recurrir a él cuando surja alguna duda en el procedimiento que se haya efectuado o en aquél que se vaya a utilizar c).- Cuando se realicen sesiones clínicas dentro de la unidad, en las que se analice defectos al nacimiento, el manual será de mucha utilidad como apoyo para lograr el objetivo de aprendizaje que se halla planteado para la sesión, ya que se pueden utilizar como base los procedimientos clínicos descritos en él d).- Es conveniente, como técnica de enseñanza individual o colectiva, tomar cada una de las tareas descritas en el manual y tratar de representarlas por medio de diagramas de flujo; si existe un solo médico en la unidad, podrá sintetizar una tarea por semana o quincena. El manual tiene com objetivo proveer al médico del Primer Nivel de Atención, de un documento que no le de información vaga sobre la atención primaria de los defectos al nacimiento, sino que le señale la forma, el cómo, con qué y cuántas veces debe realizarse un procedimiento para lograr su prevención, diagnóstico y tratamiento adecuado
Subject(s)
Primary Health Care/organization & administration , Primary Health Care , Birth Injuries/embryology , Birth Injuries/genetics , Labor, Obstetric/genetics , Mexico , Parturition/standards , Postpartum Period/genetics , Pregnancy/geneticsABSTRACT
Families with more than one individual of the same generation with the diagnosis of schizophrenia were recruited for studies. Brain lateral ventricular size was quantified in 26 schizophrenic subjects from 12 unrelated families, their available well siblings (N = 10), and 20 nonpsychotic controls. Lateral ventricular size was significantly greater in the schizophrenics than in their well siblings and controls. In addition, an analysis of variance of the data showed a significant familial component to ventricular size. Although histories of head injury and birth complications were also associated with ventricular size, these were not sufficient to explain both the familial aspect of ventricular size and the association of greater ventricular size with schizophrenia within these families.
