The autism "epidemic": Ethical, legal, and social issues in a developmental spectrum disorder.

Classic autism has gradually evolved into the concept of a larger "spectrum disorder." The rising prevalence of autism and autism spectrum disorder (autism/ASD) diagnoses can be largely attributed to broader diagnostic criteria, adoption of dimensional assessment strategies, increased awareness, linking of services to diagnosis, and the inclusion of milder neurodevelopmental differences bordering on normality. The spectrum disorder diagnosis raises numerous bioethical issues for individuals and society.

Dyscalculia and the Calculating Brain.

Dyscalculia, like dyslexia, affects some 5% of school-age children but has received much less investigative attention. In two thirds of affected children, dyscalculia is associated with another developmental disorder like dyslexia, attention-deficit disorder, anxiety disorder, visual and spatial disorder, or cultural deprivation. Infants, primates, some birds, and other animals are born with the innate ability, called subitizing, to tell at a glance whether small sets of scattered dots or other items differ by one or more item.

Autism Spectrum Disorders (ASD) in Blind Children: Very High Prevalence, Potentially Better Outlook.

Autism spectrum disorders affected 19 of 38 unselected children at a school for the blind in Cordoba, Argentina. Autism was linked to total congenital blindness, not blindness' etiology, acquired or incomplete blindness, sex, overt brain damage, or socioeconomic status. Autism "recovery," had occurred in 4 verbal children.

Classification of behaviorally defined disorders: biology versus the DSM.

Three levels of investigation underlie all biologically based attempts at classification of behaviorally defined developmental and psychiatric disorders: Level A, pseudo-categorical classification of mostly dimensional descriptions of behaviors and their disorders included in the 2013 American Psychiatric Association's Fifth Edition of the Diagnostic and Statistical Manual (DSM-5); Level C, mostly categorical classification of genetic and environmental causes (etiologies) of Level A disorders; and Level B, the pathophysiologic--both categorical and dimensional--biologic mechanisms underlying Level A "diagnoses" which comprise hierarchically interacting molecular, cellular, and neural networks and major brain pathways orchestrated by Level C etiologies. Besides modest numbers of effective psychotropic medications and their derivatives, major advances in treatment have addressed the behavioral symptoms of Level A-defined developmental and psychiatric disorders. The National Institute of Mental Health proposes support for a new biologically based Research Domain Criteria (RDoC) classification; its goal is to apply to behaviorally defined Level A developmental and psychiatric disorders the biologically based Level C and Level B research strategies that have greatly accelerated treatment and prevention of medical disorders.

Motor stereotypies and volumetric brain alterations in children with Autistic Disorder.

Motor stereotypies are defined as patterned, repetitive, purposeless movements. These stigmatizing motor behaviors represent one manifestation of the third core criterion for an Autistic Disorder (AD) diagnosis, and are becoming viewed as potential early markers of autism. Moreover, motor stereotypies might be a tangible expression of the underlying neurobiology of this neurodevelopmental disorder.

Disorders of nucleotide excision repair.

Deficient repair of ubiquitous errors in the genome risks faulty transcription or replication. Its direct and indirect phenotypic consequences are rare, complex, dementing, lethal disorders of children with inadequately understood overlapping genotypes and variable severity. Mutations of CSA or CSB responsible for impaired transcription-coupled repair cause Cockayne syndrome (CS).

Abnormalities of joint mobility and gait in children with autism spectrum disorders.

Aims: Abnormalities of gross motor function in children with autism are well known to clinicians but have not received much empirical documentation and, with the exception of stereotypies, are not among its diagnostic criteria. We recorded the characteristics of gait and prevalence of toe walking, the range of passive joint mobility, and age at walking in children with DSM IV autism spectrum disorders (ASDs) and in age- and gender-matched typically developing peers (mean age 4years 6months, range 22months-10years 9months).

Methods: We evaluated maximum range of mobility at the elbow, wrist, metacarpo-phalangeal, and ankle joints and videoed children walking and running.

Neurobiological basis of autism.

Autism (autism spectrum disorders) is a complex, strongly genetically influenced, behaviorally defined disorder of the immature brain associated with very uneven intellectual abilities. Among its most salient and potentially treatable neurologic features that this article focuses on are epilepsy, disorganized sleep patterns, and sensory and motor deficits. Its many causes and wide range of severity means that there is no symptom, no pathology, imaging, electroencephalography, or other biologic feature, and no biologic treatment that is universal or diagnostic of this developmental syndrome.

CEP41 is mutated in Joubert syndrome and is required for tubulin glutamylation at the cilium.

Tubulin glutamylation is a post-translational modification that occurs predominantly in the ciliary axoneme and has been suggested to be important for ciliary function. However, its relationship to disorders of the primary cilium, termed ciliopathies, has not been explored. Here we mapped a new locus for Joubert syndrome (JBTS), which we have designated as JBTS15, and identified causative mutations in CEP41, which encodes a 41-kDa centrosomal protein.

Child neurologists as evaluators of developmental disorders.

Child neurologists are required to evaluate and care for an increasing number of children with developmental disorders; therefore they need to be familiar with the more prevalent ones, in particular the autism spectrum disorders which may masquerade as others. Their assessment needs to include a screening mental status evaluation and reviewing a recent definitive test of hearing in all children with defective speech. Neurologists' responsibility is to make sure that there is no likely underlying problem like epilepsy, neurologic, or genetic condition that requires specific medical intervention or genetic counseling.

Brief report: life history and neuropathology of a gifted man with Asperger syndrome.

Despite recent interest in the pathogenesis of the autism spectrum disorders (pervasive developmental disorders), neuropathological descriptions of brains of individuals with well documented clinical information and without potentially confounding symptomatology are exceptionally rare. Asperger syndrome differs from classic autism by lack of cognitive impairment or delay in expressive language acquisition. We examined the 1,570 g brain of a 63 year old otherwise healthy mathematician with an Autistic Spectrum Disorder of Asperger subtype.

Male predominance in autism: neuroendocrine influences on arousal and social anxiety.

We offer a neurobiologic theory based on animal work that helps account for the conspicuous male predominance in autism spectrum disorders (ASD). In young male animals, testosterone (TST) binds to androgen receptors (AR) in brainstem neurons responsible for enhancing brain arousal. As a consequence, arousal-related neurotransmitters bombard the amygdala hypersensitized by TST acting though AR.

Neuropathology of Cockayne syndrome: Evidence for impaired development, premature aging, and neurodegeneration.

Global growth and development failure, premature, accelerated, pathologic aging, and neurodegeneration characterize Cockayne syndrome (CS) and the cerebro-oculo-facial-skeletal and xeroderma pigmentosum/CS syndromes which overlap CS partially in their genetic, somatic, and neuropathologic features. Mutations of CSA or CSB genes jeopardize transcription-coupled repair of damaged nuclear and mitochondrial DNA and resumption of replication and transcription. Resultant defective proteins or gene silencing eventuate in profound dwarfism and micrencephaly, cachexia, vasculopathy, and neurodegeneration.

Motor stereotypies in children with autism and other developmental disorders.

The purpose of the study was to count and characterize the range of stereotypies--repetitive rhythmical, apparently purposeless movements--in developmentally impaired children with and without autism, and to determine whether some types are more prevalent and diagnostically useful in children with autism. We described each motor stereotypy recorded during 15 minutes of archived videos of standardized play sessions in 277 children (209 males, 68 females; mean age 4y 6mo [SD 1y 5mo], range 2y 11mo-8y 1mo), 129 with autistic disorder (DSM-III-R), and 148 cognitively-matched non-autistic developmentally disordered (NADD) comparison children divided into developmental language disorder and non-autism, low IQ (NALIQ) sub-groups. The parts of the body involved and characteristics of all stereotypies were scored blind to diagnosis.

Convulsing toward the pathophysiology of autism.

The autisms and epilepsies are heterogeneous disorders that have diverse etiologies and pathologies. The severity of impairment and of symptoms associated with autism or with particular epilepsy syndromes reflects focal or global, structurally abnormal or dysfunctional neuronal networks. The complex relationship between autism and epilepsy, as reflected in the autism-epilepsy phenotype, provides a bridge to further knowledge of shared neuronal networks that can account for both the autisms and the epilepsies.

Autism: definition, neurobiology, screening, diagnosis.

Autism (ie, the autism spectrum disorders) is now recognized in 1 in 150 children. This article highlights the definition, neurobiology, screening, and diagnosis of autism. The genetics, immunology, imaging, and neurophysiology of autism are reviewed, with particular emphasis on areas that impact pediatricians.