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BACKGROUND: We sought to identify patient and provider factors associated with low completion of genetic testing, specifically chromosomal microarray (CMA), for autism spectrum disorder (ASD). METHODS: Medical record review was conducted of children newly diagnosed with ASD without prior genetic testing at a single academic medical center from February 2015 through January 2016. RESULTS: Only 41.9% of individuals with ASD completed CMA testing over at least 18 months from diagnosis (n = 140 of 334). Time to CMA completion varied, with a median of 86.5 days (interquartile range 2 to 214.5 days). Provider recommendation of genetic testing at the diagnostic visit and greater number of follow-up visits were associated with CMA completion. On multivariate regression, CMA completion was inversely associated with age (odds ratio [OR] = 0.8 for each year older, 95% confidence interval [CI] 0.7, 0.9; P = 0.001) and directly associated with intellectual disability or global developmental delay (OR = 2.2, 95% CI 1.3, 3.8; P = 0.004), first-degree relative with ASD (OR = 2.5, 95% CI 1.0, 6.0; P = 0.044), and public insurance (OR = 1.7, 95% CI 1.0, 2.9; P = 0.037). Parental concern and cost/insurance coverage were the most frequently documented barriers. CONCLUSIONS: Workflows to support early genetic testing recommendation and ordering soon after diagnosis may increase utilization, incorporating both family and provider perspectives. Genetic counseling highlighting the utility of genetic testing across the life span, phenotypic variability of genetic disorders, and possibility of de novo variants in ASD may also improve utilization.
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Transtorno do Espectro Autista , Deficiência Intelectual , Criança , Humanos , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/genética , Análise em Microsséries , Deficiência Intelectual/genética , Testes Genéticos , FamíliaRESUMO
OBJECTIVE: We conducted a scoping review of interventions designed to improve the health care experiences of autistic individuals and assessed the methodology and outcomes used to evaluate them. METHODS: Literature from January 2005 to October 2020 was searched using PubMed, Excerpta Medica dataBASE (EMBASE), Cumulated Index to Nursing and Allied Health Literature (CINAHL), PsycINFO as well as hand searching. Studies included described an intervention for autistic individuals in inpatient or outpatient settings and evaluated the intervention using standardized methodology. Results were exported to Covidence software. Ten reviewers completed abstract screening, full text review, and then systematic data extraction of the remaining articles. Two reviewers evaluated each article at each stage, with a third reviewer arbitrating differences. RESULTS: A total of 38 studies, including three randomized controlled trials (RCTs) were included. Twenty-six (68%) took place in dental, psychiatric, or procedural settings. Interventions primarily focused on visit preparation and comprehensive care plans or pathways (Nâ¯=â¯29, 76%). The most frequent outcome was procedural compliance (Nâ¯=â¯15), followed by intervention acceptability (Nâ¯=â¯7) and parent satisfaction (Nâ¯=â¯6). Two studies involved autistic individuals and caregivers in study design, and no studies assessed racial/ethnic diversity on intervention impact. CONCLUSIONS: Well-designed evaluations of interventions to support autistic individuals in pediatric health care settings are limited. There is a need to conduct large multi-site intervention implementation studies.
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Transtorno Autístico , Criança , Humanos , Transtorno Autístico/terapia , Satisfação Pessoal , Pacientes Internados , Atenção à SaúdeRESUMO
OBJECTIVE: Understanding the types of functional challenges faced by adolescents and young adults with disabilities (AYA-WD) can help payers, clinicians, community-based service providers, and policymakers recognize and meet needs. This paper describes state-level prevalence rates for 1) AYA-WD overall and for 2) impairment types singly and in combinations; and 3) examines how rates may differ between those insured by Medicaid versus commercial insurance. METHODS: This descriptive study uses Colorado's All Payer Claims Dataset 2014-2018 to identify insured 10- to 26-year-olds (Medicaid only: 333,931; commercially only: 392,444). It then applies the previously validated Children with Disabilities Algorithm (CWDA) and its companion, the Diagnosis-to-Impairment-Type Algorithm (DITA), to compare state-level prevalence rates by insurance source for disability overall and for each of five impairment types singly and in combination. RESULTS: Disability prevalence was greater among the Medicaid-insured AYA-WD by +7.6% points (pp)-Medicaid: 11.9% (47,654/333,931), commercial: 4.3% (16,907/392,444). Most AYA-WD had a single impairment, but the prevalence of AYA-WD with two or more impairments was greater among the Medicaid-insured than the commercially insured (+9.9 pp; Medicaid: 33.5% [15,963/47,654], commercial: 23.7% [3992/16, 907]), as was the prevalence of impairment types that were physical (+6.7 pp; Medicaid: 54.7% [26,054/47,654], commercial: 48.0% [8121/16,907]); developmental (+4.1 pp; Medicaid: 35.4% [16,874/47,654], commercial: 31.3% [5290/16,907]); psychiatric (+6.7 pp; Medicaid 21.3% [10,175/47,654], commercial: 14.6% [2470/16,907]), and intellectual (+9.3 pp; Medicaid: 26.2% [12,501/47,654], commercial: 16.9% [2858/16,907]). CONCLUSIONS: CWDA and DITA can be used to understand the rates at which impairment types and combinations occur in a population with childhood-onset disabilities.
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Background and Objectives: Deletions and duplications at 16p11.2 (BP4 to BP5; 29.5-30.1 Mb) have been associated with several neurodevelopmental and neuropsychiatric disorders including autism spectrum disorder, intellectual disability (ID), and schizophrenia. Seizures have also been reported in individuals with these particular copy number variants, but the epilepsy phenotypes have not been well-delineated. We aimed to systematically characterize the seizure types, epilepsy syndromes, and epilepsy severity in a large cohort of individuals with these 16p11.2 deletions and duplications. Methods: The cohort of ascertained participants with the recurrent 16p11.2 copy number variant was assembled through the multicenter Simons Variation in Individuals Project. Detailed data on individuals identified as having a history of seizures were obtained using a semistructured phone interview and review of medical records, EEG, and MRI studies obtained clinically or as part of the Simons Variation in Individuals Project. Results: Among 129 individuals with the 16p11.2 deletion, 31 (24%) had at least one seizure, including 23 (18%) who met criteria for epilepsy; 42% of them fit the phenotype of classic or atypical Self-limited (Familial) Infantile Epilepsy (Se(F)IE). Among 106 individuals with 16p11.2 duplications, 16 (15%) had at least one seizure, including 11 (10%) who met criteria for epilepsy. The seizure types and epilepsy syndromes were heterogeneous in this group. Most of the individuals in both the deletion and duplication groups had well-controlled seizures with subsequent remission. Pharmacoresistant epilepsy was uncommon. Seizures responded favorably to phenobarbital, carbamazepine, and oxcarbazepine in the deletion group, specifically in the Se(F)IE, and to various antiseizure medications in the duplication group. Discussion: These findings delineate the spectrum of seizures and epilepsies in the recurrent 16p11.2 deletions and duplications and provide potential diagnostic, therapeutic, and prognostic information.
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PURPOSE OF REVIEW: Autism spectrum disorder is a neurodevelopmental disorder defined by deficits in social communication and the presence of restricted and repetitive behaviors and interests. This article provides the tools to diagnose and manage patients with autism spectrum disorder. RECENT FINDINGS: Autism spectrum disorder is a heterogeneous condition with varying presentations, multiple etiologies, and a number of comorbidities that impact the course and management of the disorder. This article defines the core features of social communication deficits, including problems with social reciprocity, decreased nonverbal communication, and difficulties in developing and maintaining relationships. The second domain of repetitive behaviors and restricted interests, which includes the presence of stereotyped behaviors or speech, insistence on sameness and behavioral rigidity, intense or out of the ordinary interests, and unusual responses to sensory stimulation, is also delineated. Comorbidities commonly seen with autism spectrum disorder include medical, neurologic, and psychiatric conditions. Despite intense research efforts, the etiology of autism spectrum disorder remains unknown in most cases, but it is clear that a strong genetic component exists that interacts with various environmental risk factors. Current research is identifying overlapping neurobiological pathways that are involved in pathogenesis. Treatment involves intensive behavioral therapy and educational programming along with traditional ancillary services, such as speech/language, occupational, and physical therapies. Psychopharmacologic treatments are also used to target certain symptoms and comorbid conditions. SUMMARY: Neurologists can play an important role in diagnosing autism spectrum disorder according to clinical criteria through a comprehensive evaluation that includes a thorough medical and developmental history, behavioral and play observations, and a review of standardized cognitive and language evaluations. Neurologists are also responsible for investigating etiologies, recommending and advocating for appropriate behavioral and educational interventions, and identifying and often managing comorbidities.
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Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/terapia , Criança , Pré-Escolar , Feminino , Humanos , MasculinoRESUMO
Chromosome 16p11.2 deletions and duplications are among the most frequent genetic etiologies of autism spectrum disorder (ASD) and other neurodevelopmental disorders, but detailed descriptions of their neurologic phenotypes have not yet been completed. We utilized standardized examination and history methods to characterize a neurologic phenotype in 136 carriers of 16p11.2 deletion and 110 carriers of 16p11.2 duplication-the largest cohort to date of uniformly and comprehensively characterized individuals with the same 16p copy number variants (CNVs). The 16p11.2 deletion neurologic phenotype is characterized by highly prevalent speech articulation abnormalities, limb and trunk hypotonia with hyporeflexia, abnormalities of agility, sacral dimples, seizures/epilepsy, large head size/macrocephaly, and Chiari I/cerebellar tonsillar ectopia. Speech articulation abnormalities, hypotonia, abnormal agility, sacral dimples, and seizures/epilepsy are also seen in duplication carriers, along with more prominent hyperreflexia; less, though still prevalent, hyporeflexia; highly prevalent action tremor; small head size/microcephaly; and cerebral white matter/corpus callosum abnormalities and ventricular enlargement. The neurologic phenotypes of these reciprocal 16p11.2 CNVs include both shared and distinct features. Reciprocal phenotypic characteristics of predominant hypo- versus hyperreflexia and macro- versus microcephaly may reflect opposite neurobiological abnormalities with converging effects causing the functional impairments shared between 16p11.2 deletion and duplication carriers (i.e., abnormal motor agility and articulation). While the phenotypes exhibit overlap with other genetically-caused neurodevelopmental disorders, clinicians should be aware of the more striking features-such as the speech and motor impairments, growth abnormalities, tremor, and sacral dimples-when evaluating individuals with developmental delay, intellectual disability, ASD, and/or language disorders. © 2016 Wiley Periodicals, Inc.
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Deleção Cromossômica , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Duplicação Cromossômica , Cromossomos Humanos Par 16 , Fenótipo , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Eletroencefalografia , Epilepsia/diagnóstico , Epilepsia/genética , Feminino , Genótipo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: To examine the association between cerebral folate deficiency and autism, this study examined CSF 5-methyltetrahydrofolate (5-MTHF) concentrations in a group of young children with autism, investigated the natural variation in CSF 5-MTHF over time, and assessed the relationship between CSF 5-MTHF and symptoms. METHODS: CSF was collected from 67 children with a diagnosis of DSM-IV-TR autistic disorder (age, mean ± SD 43 ± 11 months), with a second CSF sample obtained 1-3 years later on 31 of these subjects (time to follow-up, 30 ± 8 months). RESULTS: At time 1, 7% (5/67) of participants had 5-MTHF <40 nmol/L. At follow-up, 23% (7/31) of participants had 5-MTHF <40 nmol/L (only one of whom had been low at time 1). A moderate correlation with a very wide confidence interval (CI) was observed between time 1 and time 2 CSF 5-MTHF measurements (Pearson r[p] = 0.38 [0.04]; 95% CI 0.02-0.64). Neither the CSF 5-MTHF levels nor changes over time correlated with the clinical features of autism. CONCLUSIONS: CSF 5-MTHF levels vary significantly over time in an unpredictable fashion and do not show a significant relationship to typical clinical features of autism. Reduced CSF 5-MTHF levels are a nonspecific finding in autism. Our data do not support the use of lumbar puncture for assessment of CSF 5-MTHF in autism.
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Transtorno Autístico/líquido cefalorraquidiano , Tetra-Hidrofolatos/líquido cefalorraquidiano , Transtorno Autístico/sangue , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Criança , Pré-Escolar , Ácido Fólico/sangue , Seguimentos , Humanos , Estudos Longitudinais , Testes Neuropsicológicos , Índice de Gravidade de DoençaRESUMO
IMPORTANCE: The 16p11.2 BP4-BP5 duplication is the copy number variant most frequently associated with autism spectrum disorder (ASD), schizophrenia, and comorbidities such as decreased body mass index (BMI). OBJECTIVES: To characterize the effects of the 16p11.2 duplication on cognitive, behavioral, medical, and anthropometric traits and to understand the specificity of these effects by systematically comparing results in duplication carriers and reciprocal deletion carriers, who are also at risk for ASD. DESIGN, SETTING, AND PARTICIPANTS: This international cohort study of 1006 study participants compared 270 duplication carriers with their 102 intrafamilial control individuals, 390 reciprocal deletion carriers, and 244 deletion controls from European and North American cohorts. Data were collected from August 1, 2010, to May 31, 2015 and analyzed from January 1 to August 14, 2015. Linear mixed models were used to estimate the effect of the duplication and deletion on clinical traits by comparison with noncarrier relatives. MAIN OUTCOMES AND MEASURES: Findings on the Full-Scale IQ (FSIQ), Nonverbal IQ, and Verbal IQ; the presence of ASD or other DSM-IV diagnoses; BMI; head circumference; and medical data. RESULTS: Among the 1006 study participants, the duplication was associated with a mean FSIQ score that was lower by 26.3 points between proband carriers and noncarrier relatives and a lower mean FSIQ score (16.2-11.4 points) in nonproband carriers. The mean overall effect of the deletion was similar (-22.1 points; P < .001). However, broad variation in FSIQ was found, with a 19.4- and 2.0-fold increase in the proportion of FSIQ scores that were very low (≤40) and higher than the mean (>100) compared with the deletion group (P < .001). Parental FSIQ predicted part of this variation (approximately 36.0% in hereditary probands). Although the frequency of ASD was similar in deletion and duplication proband carriers (16.0% and 20.0%, respectively), the FSIQ was significantly lower (by 26.3 points) in the duplication probands with ASD. There also were lower head circumference and BMI measurements among duplication carriers, which is consistent with the findings of previous studies. CONCLUSIONS AND RELEVANCE: The mean effect of the duplication on cognition is similar to that of the reciprocal deletion, but the variance in the duplication is significantly higher, with severe and mild subgroups not observed with the deletion. These results suggest that additional genetic and familial factors contribute to this variability. Additional studies will be necessary to characterize the predictors of cognitive deficits.
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Transtorno do Espectro Autista/psicologia , Transtorno Autístico/psicologia , Transtornos Cromossômicos/psicologia , Duplicação Cromossômica , Cromossomos Humanos Par 16/genética , Cognição , Deficiência Intelectual/psicologia , Esquizofrenia/genética , Adolescente , Adulto , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/genética , Transtorno Autístico/epidemiologia , Transtorno Autístico/genética , Estudos de Casos e Controles , Cerebelo/anormalidades , Criança , Pré-Escolar , Deleção Cromossômica , Transtornos Cromossômicos/epidemiologia , Transtornos Cromossômicos/genética , Estudos de Coortes , Comorbidade , Variações do Número de Cópias de DNA , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/genética , Epilepsia/epidemiologia , Epilepsia/genética , Feminino , Humanos , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/genética , Masculino , Microcefalia/epidemiologia , Microcefalia/genética , Pessoa de Meia-Idade , Malformações do Sistema Nervoso/epidemiologia , Malformações do Sistema Nervoso/genética , Esquizofrenia/epidemiologia , Psicologia do Esquizofrênico , Adulto JovemRESUMO
The association between autism spectrum disorder (ASD) and epilepsy has been described for decades, and yet we still lack the full understanding of this relationship both clinically and at the pathophysiologic level. This review evaluates the available data in the literature pertaining to the clinical characteristics of patients with autism spectrum disorder who develop epilepsy and, conversely, patients with epilepsy who develop autism spectrum disorder. Many studies demonstrate an increased risk of epilepsy in individuals with ASD, but rates vary widely. This variability is likely secondary to the different study methods employed, including the study population and definitions of the disorders. Established risk factors for an increased risk of epilepsy in patients with ASD include intellectual disability and female gender. There is some evidence of an increased risk of epilepsy associated with other factors such as ASD etiology (syndromic), severity of autistic features, developmental regression, and family history. No one epilepsy syndrome or seizure type has been associated, although focal or localization-related seizures are often reported. The age at seizure onset can vary from infancy to adulthood with some evidence of a bimodal age distribution. The severity and intractability of epilepsy in populations with ASD have not been well studied, and there is very little investigation of the role that epilepsy plays in the autism behavioral phenotype. There is evidence of abnormal EEGs (especially epileptiform abnormalities) in children with ASD even in the absence of clinical seizures, but very little is known about this phenomenon and what it means. The development of autism spectrum disorder in patients with epilepsy is less well studied, but there is evidence that the ASD risk is greater in those with epilepsy than in the general population. One of the risk factors is intellectual disability, and there is some evidence that the presence of a particular seizure type, infantile spasms, may increase risk, but some of the data are conflicting. We believe that one of the reasons that so little is known about this phenomenon is the lack of cross talk between researchers and clinicians alike in the two fields. We conclude that large systematic studies that employ strict ascertainment of samples using standardized definitions of both disorders, validated data collection tools, and appropriate longitudinal follow-up are needed to better shed light on certain clinical aspects of the comorbidity of ASD and epilepsy. Ideally, we could provide the optimal diagnostic and treatment services to these patients in a multidisciplinary setting with both epilepsy and neurobehavioral specialists. This article is part of a Special Issue entitled "Autism and Epilepsy".
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Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/psicologia , Epilepsia/complicações , Epilepsia/psicologia , Transtorno do Espectro Autista/epidemiologia , Criança , Epilepsia/epidemiologia , Humanos , Adulto JovemRESUMO
OBJECTIVE: Seizures are common in individuals with duplications of chromosome 15q11.2-q13 (Dup15q). The goal of this study was to examine the phenotypes and treatments of seizures in Dup15q in a large population. METHODS: A detailed electronic survey was conducted through the Dup15q Alliance containing comprehensive questions regarding seizures and their treatments in Dup15q. RESULTS: There were 95 responses from Dup15q families. For the 83 with idic(15), 63% were reported to have seizures, of which 81% had multiple seizure types and 42% had infantile spasms. Other common seizure types were tonic-clonic, atonic, myoclonic, and focal. Only 3 of 12 individuals with int dup(15) had seizures. Broad spectrum antiepileptic drugs (AEDs) were the most effective medications, but carbamazepine and oxcarbazepine were also effective, although typical benzodiazepines were relatively ineffective. There was a 24% response rate (>90% seizure reduction) to the first AED tried. For those with infantile spasms, adrenocorticotropic hormone (ACTH) was more effective than vigabatrin. SIGNIFICANCE: This is the largest study assessing seizures in Duplication 15q syndrome, but because this was a questionnaire-based study with a low return rate, it is susceptible to bias. Seizures are common in idic(15) and typically difficult to control, often presenting with infantile spasms and progressing to a Lennox-Gastaut-type syndrome. Seizures in those with int dup(15) are less common, with a frequency similar to the general autism population. In addition to broad spectrum AED, medications such as carbamazepine and oxcarbazepine are also relatively effective in controlling seizures in this population, suggesting a possible multifocal etiology, which may also explain the high rate of infantile spasms. Our small sample suggests a relative lack of efficacy of vigabatrin and other γ-aminobutyric acid (GABA)ergic medications, such as typical benzodiazepines, which may be attributable to abnormal GABAergic transmission resulting from the duplication of a cluster of GABAß3 receptor genes in the 15q11.2-13 region.
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Anticonvulsivantes/uso terapêutico , Coleta de Dados/métodos , Convulsões/tratamento farmacológico , Convulsões/genética , Trissomia/genética , Adolescente , Criança , Pré-Escolar , Cromossomos Humanos Par 15/genética , Feminino , Humanos , Masculino , Convulsões/diagnóstico , Síndrome , Resultado do TratamentoRESUMO
Epilepsy is common in children with autism spectrum disorder (ASD) but little is known about how seizures impact the autism phenotype. The association between epilepsy and autism symptoms and associated maladaptive behaviors was examined in 2,645 children with ASD, of whom 139 had epilepsy, from the Simons Simplex Collection. Children with ASD and epilepsy had significantly more autism symptoms and maladaptive behaviors than children without epilepsy. However, after adjusting for IQ, only hyperactivity symptoms remained significantly increased (13% higher) in the epilepsy group. Among children with ASD without co-occurring intellectual disability, children with epilepsy had significantly more irritability (20% higher) and hyperactivity (24% higher) symptoms. This is the largest study to date comparing the autism phenotype in children with ASD with and without epilepsy. Children with ASD and epilepsy showed greater impairment than children without epilepsy, which was mostly explained by the lower IQ of the epilepsy group. These findings have important clinical implications for patients with ASD.
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Transtornos do Comportamento Infantil/epidemiologia , Transtornos Globais do Desenvolvimento Infantil/epidemiologia , Epilepsia/epidemiologia , Adolescente , Criança , Pré-Escolar , Comorbidade , Feminino , Humanos , Deficiência Intelectual/epidemiologia , Masculino , Estados Unidos/epidemiologiaRESUMO
OBJECTIVES: To estimate the prevalence of epilepsy in children with Autism Spectrum Disorder (ASD) and to determine the demographic and clinical characteristics of children with ASD and epilepsy in a large patient population. METHODS: Cross-sectional study using four samples of children with ASD for a total of 5,815 participants with ASD. The prevalence of epilepsy was estimated from a population-based sample. Children with and without epilepsy were compared on demographic and clinical characteristics. Multivariate logistic regression was used to examine the association between demographic and clinical characteristics and epilepsy. RESULTS: The average prevalence of epilepsy in children with ASD 2-17 years was 12.5%; among children aged 13 years and older, 26% had epilepsy. Epilepsy was associated with older age, lower cognitive ability, poorer adaptive and language functioning, a history of developmental regression and more severe ASD symptoms. The association between epilepsy and the majority of these characteristics appears to be driven by the lower IQ of participants with epilepsy. In a multivariate regression model, only age and cognitive ability were independently associated with epilepsy. Children age 10 or older had 2.35 times the odds of being diagnosed with epilepsy (p<.001) and for a one standard deviation increase in IQ, the odds of having epilepsy decreased by 47% (p<.001). CONCLUSION: This is among the largest studies to date of patients with ASD and co-occurring epilepsy. Based on a representative sample of children with ASD, the average prevalence of epilepsy is approximately 12% and reaches 26% by adolescence. Independent associations were found between epilepsy and older age and lower cognitive ability. Other risk factors, such as poor language and developmental regression, are not associated with epilepsy after controlling for IQ. These findings can help guide prognosis and alert clinicians to patients with ASD who are at increased risk for epilepsy.
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Transtornos Globais do Desenvolvimento Infantil/fisiopatologia , Cognição , Epilepsia/fisiopatologia , Adolescente , Criança , Transtornos Globais do Desenvolvimento Infantil/complicações , Transtornos Globais do Desenvolvimento Infantil/epidemiologia , Pré-Escolar , Estudos Transversais , Epilepsia/complicações , Epilepsia/epidemiologia , Feminino , Humanos , Desenvolvimento da Linguagem , Masculino , Vigilância da População , Prevalência , Prognóstico , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: The recurrent ~600 kb 16p11.2 BP4-BP5 deletion is among the most frequent known genetic aetiologies of autism spectrum disorder (ASD) and related neurodevelopmental disorders. OBJECTIVE: To define the medical, neuropsychological, and behavioural phenotypes in carriers of this deletion. METHODS: We collected clinical data on 285 deletion carriers and performed detailed evaluations on 72 carriers and 68 intrafamilial non-carrier controls. RESULTS: When compared to intrafamilial controls, full scale intelligence quotient (FSIQ) is two standard deviations lower in carriers, and there is no difference between carriers referred for neurodevelopmental disorders and carriers identified through cascade family testing. Verbal IQ (mean 74) is lower than non-verbal IQ (mean 83) and a majority of carriers require speech therapy. Over 80% of individuals exhibit psychiatric disorders including ASD, which is present in 15% of the paediatric carriers. Increase in head circumference (HC) during infancy is similar to the HC and brain growth patterns observed in idiopathic ASD. Obesity, a major comorbidity present in 50% of the carriers by the age of 7 years, does not correlate with FSIQ or any behavioural trait. Seizures are present in 24% of carriers and occur independently of other symptoms. Malformations are infrequently found, confirming only a few of the previously reported associations. CONCLUSIONS: The 16p11.2 deletion impacts in a quantitative and independent manner FSIQ, behaviour and body mass index, possibly through direct influences on neural circuitry. Although non-specific, these features are clinically significant and reproducible. Lastly, this study demonstrates the necessity of studying large patient cohorts ascertained through multiple methods to characterise the clinical consequences of rare variants involved in common diseases.
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Transtornos Globais do Desenvolvimento Infantil/genética , Deleção Cromossômica , Cromossomos Humanos Par 16 , Deficiências do Desenvolvimento/genética , Fenótipo , Adolescente , Adulto , Índice de Massa Corporal , Criança , Transtornos Globais do Desenvolvimento Infantil/diagnóstico , Deficiências do Desenvolvimento/diagnóstico , Feminino , Ordem dos Genes , Heterozigoto , Humanos , Testes de Inteligência , Masculino , Síndrome , Adulto JovemRESUMO
The challenges of gathering in-vivo measures of brain anatomy from young children have limited the number of independent studies examining neuroanatomical differences between children with autism and typically developing controls (TDCs) during early life, and almost all studies in this critical developmental window focus on global or lobar measures of brain volume. Using a novel cohort of young males with Autistic Disorder and TDCs aged 2 to 5 years, we (i) tested for group differences in traditional measures of global anatomy (total brain, total white, total gray and total cortical volume), and (ii) employed surface-based methods for cortical morphometry to directly measure the two biologically distinct sub-components of cortical volume (CV) at high spatial resolution-cortical thickness (CT) and surface area (SA). While measures of global brain anatomy did not show statistically significant group differences, children with autism showed focal, and CT-specific anatomical disruptions compared to TDCs, consisting of relative cortical thickening in regions with central roles in behavioral regulation, and the processing of language, biological movement and social information. Our findings demonstrate the focal nature of brain involvement in early autism, and provide more spatially and morphometrically specific anatomical phenotypes for subsequent translational study.
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PURPOSE OF REVIEW: Autism spectrum disorders (ASDs) are heterogeneous neurodevelopmental disorders associated with various co-morbidities. Neurological co-morbidities include motor impairments, epilepsy, and sleep dysfunction. These impairments have been receiving more attention recently, perhaps because of their significant impact on the behavior and cognitive function of children with ASDs. Here, we review the epidemiology, etiology, and clinical approach to these neurological co-morbidities and highlight future research directions. RECENT FINDINGS: Motor impairments include stereotypies, motor delays, and deficits, such as dyspraxia, incoordination, and gait problems. Sleep dysfunction typically presents as difficulty with sleep onset and prolonged awakenings during the night. Recent data suggest that abnormalities in melatonin may affect sleep and may be a potential treatment target. There is no classic epilepsy syndrome associated with ASDs. Intellectual disability, syndromic autism, and female sex are specific risk factors. Recent research has focused on identifying the overlapping pathways between these neurological co-morbidities and the core deficits in ASDs, which may have direct and powerful implications for treatment and prognosis. SUMMARY: Motor impairment, epilepsy, and sleep dysfunction are common neurological co-morbidities in ASDs. Clinicians should be aware that recognition and treatment of these issues may improve the function and outcome of children with ASDs.
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Apraxias/epidemiologia , Transtornos Globais do Desenvolvimento Infantil/epidemiologia , Epilepsia/epidemiologia , Transtornos Mentais/epidemiologia , Transtornos do Sono-Vigília/epidemiologia , Criança , Comorbidade , HumanosAssuntos
Terapia Comportamental/métodos , Comportamento Infantil , Transtornos Globais do Desenvolvimento Infantil , Terapias Complementares/métodos , Técnicas de Diagnóstico Neurológico , Criança , Transtornos Globais do Desenvolvimento Infantil/diagnóstico , Transtornos Globais do Desenvolvimento Infantil/psicologia , Transtornos Globais do Desenvolvimento Infantil/terapia , HumanosRESUMO
Autism is a neurodevelopmental disorder of unknown etiology characterized by social and communication deficits and the presence of restricted interests/repetitive behaviors. Higher rates of epilepsy have long been reported, but prevalence estimates vary from as little as 5% to as much as 46%. This variation is probably the result of sample characteristics that increase epilepsy risk such as sample ascertainment, lower intelligence quotient (IQ), the inclusion of patients with nonidiopathic autism, age, and gender. However, critical review of the literature reveals that the rate in idiopathic cases with normal IQ is still significantly above the population risk suggesting that autism itself is associated with an increased risk of epilepsy. Recently, there has been interest in the occurrence of epileptiform electroencephalograms (EEGs) even in the absence of epilepsy. Rates as high as 60% have been reported and some investigators propose that these abnormalities may play a causal role in the autism phenotype. Although this phenomenon is still not well understood and risk factors have yet to be determined, the treatment implications are increasingly important. We review the recent literature to elucidate possible risk factors for both epilepsy and epileptiform EEGs. We then review existing data and discuss controversies surrounding treatment of EEG abnormalities.