Infantile Autism and the Fragile X Syndrome in Japanese Children

A total of 97 children with infantile autism, 85 boys and 12 girls, were screened for the fragile X chromosome. They ranged in age from 2 to 14 years with an average of 5 5/12 years. There were two fra(X) positive boys and no such girls. ( Acta Paediatr Jpn 1989; 31: 163 - 165)     

Incidence of Minor Physical Anomalies in Patients With Early Infantile Autism

The incidence of 28 minor physical anomalies was examined in 118 patients with early infantile autism, 132 patients with 21 trisomy, and 237 normal subjects. Although the incidence of minor physical anomalies in children with early infantile autism was slightly higher than in the group of normal subjects, there was no significant difference between the groups. It was suggested from these findings that there is little possibility of the onset of early infantile autism being due to environmental insults at the embryonic period when minor physical anomalies are formed, and that there is no possibility of minor physical anomalies giving a clue as to the time of onset of early infantile autism. The incidence of minor physical anomalies in patients with 21 trisomy was significantly higher than in the group of normal subjects and of children with early infantile autism (p < 0.00l). Fra (X) was noted in two patients among 40 examined. These patients were not included among the subjects in the present study.     

Pervasive developmental disorders not otherwise specified. A developmental-psychopathological approach for the development of made-to-measure treatment planning.

Diagnosis and classification of autism and related pervasive developmental disorders is both easy and difficult. Infantile autism is a characteristic syndrome on which many publications have appeared in the last 50 years. Conversely, the diagnosis and even the classification of children with pervasive developmental disorders related to autism is difficult. Although children with these disorders are twice as numerous as children with infantile autism, growing attention has been directed to at the latter group since the last decade. In this paper, autism and related disorders are described as a developmental disorder as well as a spectrum disorder. The spectrum of clinical symptoms can be explained, of which infantile autism is the most severe and prototypical manifestation. A working model is presented which accounts for all the problems of children with pervasive developmental disorders. An illustration of working with the model in practice is also given. The main lines of treatment and stages in treatment are briefly described.     

An Epidemiological Study of Infantile Autism in a French Department (Rhône): Research Note

In a French Department (Rh?ne), the prevalence of infantile autism was found to be 10.8 per 10,000 in the 5-9 age group, using broad operational criteria. The prevalence decreases to 5.1 per 10,000 when another set of criteria, similar to DSM-III, is used. The boy/girl sex ratios for these two sets of criteria were 2.1:1 and 2.3:1 respectively. The use of DSM-III turned out to be problematic for taking into account a broad spectrum of early psychotic disorders, autistic-like, yet more polymorphous. A subdivision concerning the existence of associated major neurological anomalies has appeared promising but requires finer validation.     

INFANTILE AUTISM AND OTHER CHILDHOOD PSYCHOSES IN A SWEDISH URBAN REGION. EPIDEMIOLOGICCAL ASPECTS

A total population screening of children born during 1962-1976 and living in the Gothenburg region at the end of 1980 was carried out in order to obtain prevalence figures for infantile autism and other childhood psychoses. It was found that the prevalence figure for infantile autism was 2.0 per 10,000 and for other childhood psychoses 1.9 per 10,000. Boys were much more often affected by infantile autism than girls. In the case of other psychoses, no such over-representation was seen. A majority of the children were mentally retarded, and only 4% had tested IQs exceeding 100. The results are in good agreement with the three earlier epidemiological studies concerned with childhood psychosis.     

The genetics of autism

Autism is a complex, behaviorally defined, static disorder of the immature brain that is of great concern to the practicing pediatrician because of an astonishing 556% reported increase in pediatric prevalence between 1991 and 1997, to a prevalence higher than that of spina bifida, cancer, or Down syndrome. This jump is probably attributable to heightened awareness and changing diagnostic criteria rather than to new environmental influences. Autism is not a disease but a syndrome with multiple nongenetic and genetic causes. By autism (the autistic spectrum disorders [ASDs]), we mean the wide spectrum of developmental disorders characterized by impairments in 3 behavioral domains: 1) social interaction; 2) language, communication, and imaginative play; and 3) range of interests and activities. Autism corresponds in this article to pervasive developmental disorder (PDD) of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition and International Classification of Diseases, Tenth Revision. Except for Rett syndrome--attributable in most affected individuals to mutations of the methyl-CpG-binding protein 2 (MeCP2) gene--the other PDD subtypes (autistic disorder, Asperger disorder, disintegrative disorder, and PDD Not Otherwise Specified [PDD-NOS]) are not linked to any particular genetic or nongenetic cause. Review of 2 major textbooks on autism and of papers published between 1961 and 2003 yields convincing evidence for multiple interacting genetic factors as the main causative determinants of autism. Epidemiologic studies indicate that environmental factors such as toxic exposures, teratogens, perinatal insults, and prenatal infections such as rubella and cytomegalovirus account for few cases. These studies fail to confirm that immunizations with the measles-mumps-rubella vaccine are responsible for the surge in autism. Epilepsy, the medical condition most highly associated with autism, has equally complex genetic/nongenetic (but mostly unknown) causes. Autism is frequent in tuberous sclerosis complex and fragile X syndrome, but these 2 disorders account for but a small minority of cases. Currently, diagnosable medical conditions, cytogenetic abnormalities, and single-gene defects (eg, tuberous sclerosis complex, fragile X syndrome, and other rare diseases) together account for <10% of cases. There is convincing evidence that "idiopathic" autism is a heritable disorder. Epidemiologic studies report an ASD prevalence of approximately 3 to 6/1000, with a male to female ratio of 3:1. This skewed ratio remains unexplained: despite the contribution of a few well characterized X-linked disorders, male-to-male transmission in a number of families rules out X-linkage as the prevailing mode of inheritance. The recurrence rate in siblings of affected children is approximately 2% to 8%, much higher than the prevalence rate in the general population but much lower than in single-gene diseases. Twin studies reported 60% concordance for classic autism in monozygotic (MZ) twins versus 0 in dizygotic (DZ) twins, the higher MZ concordance attesting to genetic inheritance as the predominant causative agent. Reevaluation for a broader autistic phenotype that included communication and social disorders increased concordance remarkably from 60% to 92% in MZ twins and from 0% to 10% in DZ pairs. This suggests that interactions between multiple genes cause "idiopathic" autism but that epigenetic factors and exposure to environmental modifiers may contribute to variable expression of autism-related traits. The identity and number of genes involved remain unknown. The wide phenotypic variability of the ASDs likely reflects the interaction of multiple genes within an individual's genome and the existence of distinct genes and gene combinations among those affected. There are 3 main approaches to identifying genetic loci, chromosomal regions likely to contain relevant genes: 1) whole genome screens, searching for linkage of autism to shared genetic markers in populations of multiplex families (families with >1 affected family member; 2) cytogenetic studies that may guide molecular studies by pointing to relevant inherited or de novo chromosomal abnormalities in affected individuals and their families; and 3) evaluation of candidate genes known to affect brain development in these significantly linked regions or, alternatively, linkage of candidate genes selected a priori because of their presumptive contribution to the pathogenesis of autism. Data from whole-genome screens in multiplex families suggest interactions of at least 10 genes in the causation of autism. Thus far, a putative speech and language region at 7q31-q33 seems most strongly linked to autism, with linkages to multiple other loci under investigation. Cytogenetic abnormalities at the 15q11-q13 locus are fairly frequent in people with autism, and a "chromosome 15 phenotype" was described in individuals with chromosome 15 duplications. Among other candidate genes are the FOXP2, RAY1/ST7, IMMP2L, and RELN genes at 7q22-q33 and the GABA(A) receptor subunit and UBE3A genes on chromosome 15q11-q13. Variant alleles of the serotonin transporter gene (5-HTT) on 17q11-q12 are more frequent in individuals with autism than in nonautistic populations. In addition, animal models and linkage data from genome screens implicate the oxytocin receptor at 3p25-p26. Most pediatricians will have 1 or more children with this disorder in their practices. They must diagnose ASD expeditiously because early intervention increases its effectiveness. Children with dysmorphic features, congenital anomalies, mental retardation, or family members with developmental disorders are those most likely to benefit from extensive medical testing and genetic consultation. The yield of testing is much less in high-functioning children with a normal appearance and IQ and moderate social and language impairments. Genetic counseling justifies testing, but until autism genes are identified and their functions are understood, prenatal diagnosis will exist only for the rare cases ascribable to single-gene defects or overt chromosomal abnormalities. Parents who wish to have more children must be told of their increased statistical risk. It is crucial for pediatricians to try to involve families with multiple affected members in formal research projects, as family studies are key to unraveling the causes and pathogenesis of autism. Parents need to understand that they and their affected children are the only available sources for identifying and studying the elusive genes responsible for autism. Future clinically useful insights and potential medications depend on identifying these genes and elucidating the influences of their products on brain development and physiology.     

Self-organisation of cognitive processes and psychosis. Development and test of a theoretical model.

The development of a theory of self-control of brain processes leads to a model of disturbance of integration of brain processes in psychotic persons. The theory is that the "novelty-familiarity relation" of the current state of the processed information normally dominates the current mode of information processing. In the second part of the study adults with schizophrenia in remission and children with infantile autism were tested as to the manner in which they used newly introduced elements. The psychotic persons took the different character of the new elements less into consideration. The difference from the normal control persons is significant.     

Infantile autism in Kenya

Clinical features of infantile autism in three African children from Kenya are described. There is no essential difference in features of childhood autism as described in the west. In this prospective study the authors were able to confirm the onset of major symptoms of infantile autism before the age of three years and also an upper socio-economic background of the parents of all three cases.     

Infantile autism in Kenya

Clinical features of infantile autism in three African children from Kenya are described. There is no essential difference in features of childhood autism as described in the west. In this prospective study the authors were able to confirm the onset of major symptoms of infantile autism before the age of three years and also an upper socio-economic background of the parents of all three cases.     

Gait in children with infantile/atypical autism: Age-dependent decrease in gait variability and associations with motor skills

Gait and its associations with prewalking motor milestones, motor skills, and age were investigated in 32 children with infantile/atypical autism and 36 typically developing controls. Gait was assessed using GAITRite recordings of spatiotemporal and variability gait parameters. Parents reported their child's prewalking motor milestones. Motor skills were assessed using the Movement Assessment Battery for Children. Children with infantile/atypical autism showed higher gait variability than controls, indicating a less regular walking pattern. In children with infantile/atypical autism gait variability was negatively associated with motor skills, but there was no such association with prewalking motor milestones. The higher gait variability in children with infantile/atypical autism showed an age-dependent decrease, suggesting that their gait regularity converges toward that of typically developing children.     

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??Abstract?? Objective To investigate the occurrence of comorbidity in school-aged children with high-functioning and low-functioning autism disorder. Methods Sixty-two outpatients in Peking University Institute of Mental Health?? aged 6 to 16 years old?? meeting the criteria of the Diagnostic and Statistical Manual of Mental Disorders?? Fourth Edition??DSM-IV?? visiting the hospital for autism were included in this cross-sectional study from September 2011 to November 2011. They were assessed with the self-made general condition questionnaire and Chinese Wechsler Intelligence Scale for Children ??WISC??. Raven’s Standard Progressive Matrices??SPM????Stanford-Binet Intelligence Scale and Peabody picture vocabulary test??PPVT?? were performed for patients who could not perform WISC test??. Kiddie-Sade-Present and Lifetime Version ??K-SADS-PL?? ?? Child-Global Assessment Scale??C-GAS ??and Childhood Autism Rating Scale??CARS?? were also performed. Results The lifetime prevalence and current prevalence of comorbidity in high-functioning autism??HFA?? group??IQ≥70??were 100%??29/29?? and 96.5%??28/29?? respectively. The lifetime prevalence and current prevalence of comorbidity in low-functioning autism??LFA?? group??IQ??70??were all 100%??33/33??. The lifetime prevalence and current prevalence of mood disorders?? anxiety disorders?? generalized anxiety disorder?? attention deficit hyperactivity disorder?? oppositional defiant disorder and tic disorders in high-functioning autism group were higher those of low-functioning autism group ??all P??0.05??. High-functioning autism group had more psychiatric medication taking history and poor development history?? higher current percentage of attending school??and lower CARS score and higher C-GAS score than low-functioning autism group ??all P??0.05??. Conclusion Comorbidity in school-aged children with high-functioning and low-functioning autism disorder are very common. Children with high-functioning autism disorder have more emotional and behavior disorders?? milder symptoms of autism?? more psychiatric medication taking history?? and higher overall function than children with low-functioning autism disorder.     

Autism medical comorbidities

Medical comorbidities are more common in children with autism spectrum disorders (ASD) than in the general population. Some genetic disorders are more common in children with ASD such as Fragile X syndrome, Down syndrome, Duchenne muscular dystrophy, neurofibromatosis type I, and tuberous sclerosis complex. Children with autism are also more prone to a variety of neurological disorders, including epilepsy, macrocephaly, hydrocephalus, cerebral palsy, migraine/headaches, and congenital abnormalities of the nervous system. Besides, sleep disorders are a significant problem in individuals with autism, occurring in about 80% of them. Gastrointestinal (GI) disorders are significantly more common in children with ASD; they occur in 46% to 84% of them. The most common GI problems observed in children with ASD are chronic constipation, chronic diarrhoea, gastroesophageal reflux and/or disease, nausea and/or vomiting, flatulence, chronic bloating, abdominal discomfort, ulcers, colitis, inflammatory bowel disease, food intolerance, and/or failure to thrive. Several categories of inborn-errors of metabolism have been observed in some patients with autism including mitochondrial disorders, disorders of creatine metabolism, selected amino acid disorders, disorders of folate or B12 metabolism, and selected lysosomal storage disorders. A significant proportion of children with ASD have evidence of persistent neuroinflammation, altered inflammatory responses, and immune abnormalities. Anti-brain antibodies may play an important pathoplastic mechanism in autism. Allergic disorders are significantly more common in individuals with ASD from all age groups. They influence the development and severity of symptoms. They could cause problematic behaviours in at least a significant subset of affected children. Therefore, it is important to consider the child with autism as a whole and not overlook possible symptoms as part of autism. The physician should rule out the presence of a medical condition before moving on to other interventions or therapies. Children who enjoy good health have a better chance of learning. This can apply to all children including those with autism.     

西安市城区托幼机构孤独症谱系障碍儿童现患率调查

目的:了解西安市城区托幼机构儿童中孤独症谱系障碍(ASD)的患病情况。方法:采用分层整群抽样方法,在西安市6个城区抽取12所幼儿园,先采用儿童家长对数据填写孤独症行为评定量表(ABC)及保教人员报告的方法确定ASD初筛阳性儿童,然后专科医师现场行为观察确定可疑ASD儿童,最后至医院行孤独症诊断观察量表第2版(ADOS-...     

Prevalence of overweight in children and adolescents with attention deficit hyperactivity disorder and autism spectrum disorders: a chart review

Background  

The condition of obesity has become a significant public health problem in the United States. In children and adolescents, the prevalence of overweight has tripled in the last 20 years, with approximately 16.0% of children ages 6–19, and 10.3% of 2–5 year olds being considered overweight. Considerable research is underway to understand obesity in the general pediatric population, however little research is available on the prevalence of obesity in children with developmental disorders. The purpose of our study was to determine the prevalence of overweight among a clinical population of children diagnosed with attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD).     

Tuberous Sclerosis Complex in Autism

Objective

To study the prevalence rate of tuberous sclerosis complex in autistic disorder.

Methods

We studied one cohort of children followed up since 2005 until 2009, with autistic disorder, to determine the incidence of tuberous sclerosis complex. We established an autistic disorder registry in 2005 at China Rehabilitation Research Center. During the 4-year period (2005–2009), we collected a database of 429 children (390 boys and 39 girls; male to female ratio 10:1) with autistic disorder and pervasive developmental disorders. We routinely examined all children with autistic disorder for any features of tuberous sclerosis complex by looking for neurocutaneous markers such as depigmented spots. In those with infantile spasm or epilepsy, the clinical features of tuberous sclerosis complex were monitored regularly during follow-up.

Findings

Of these, five had tuberous sclerosis complex. Thus, the prevalence rate of tuberous sclerosis complex in autistic disorder is 1.17%. All of these children were mentally retarded with moderate to severe grades. Their IQ or developmental quotient was less than 70.

Conclusion

The prevalence rate of tuberous sclerosis complex in autistic disorder was 1.17% in our region; autism spectrum disorder is a condition that might be associated with development of tuberous sclerosis complex.     

Neurofibromatosis in infantile autism and other types of childhood psychoses.

Recent findings have suggested that the simultaneous occurrence of neurofibromatosis and childhood psychosis might be more than a coincidence. In this study of 341 children with infantile autism and other types of childhood psychosis seen as inpatients in two university clinics of child psychiatry in a 25-year period, only one case (0.3%) of concomitant occurrence of the disorders was found, which is a frequency no higher than expected by chance.     

Platelet serotonin concentration in children under 5 years of age]

High platelet serotonin concentrations have been reported in children with early infantile autism. However, as yet there are no reference values regarding platelet serotonin in normal infants and young children so that it remains difficult to define the exact significance of this finding. We report here with the platelet serotonin concentration found in 57 infants and children (20 girls, 37 boys) ranging in age from 10 days to 5 years old. Our results show that mean platelet serotonin concentrations in infants and young children are significantly greater than mean values obtained in older children (+11%) and neonates in the umbilical cord (+64%). No significant variations were found relating to sex, leucocyte count and platelet count. There therefore appears to be a physiological elevation of platelet serotonin concentration in infants and young children, and this has to be taken into consideration in the interpretation of the elevated values found in cases of infantile autism.     

高功能与低功能学龄期孤独症儿童共患病研究

目的 了解学龄期高功能与低功能孤独症儿童共患病的发生情况。方法 采用横断面研究,对2011年9月至2011年11月北京大学精神卫生研究所门诊连续就诊、能够配合检查的62例孤独症儿童,年龄6～16岁、符合美国精神障碍诊断与统计手册第4版（DSM-IV）中孤独症诊断标准的儿童进行调查和评定。内容包括：一般状况调查、中国修订韦氏儿童智力量表（WISC）评定（不能进行韦氏测查者进行瑞文标准推理测验、比奈测验或图片词汇测验评定）、学龄儿童情感障碍和精神分裂症问卷（K-SADS-PL）评定、儿童总评问卷（C-GAS）评定、儿童孤独症评定量表（CARS）评定。结果 高功能孤独症组（IQ≥70）共患病终生共患率100%（29/29）,目前共患率为96.5%（28/29）。低功能孤独症组（IQ＜70）共患病终生共患率及目前共患率均为100%（33/33）。高功能孤独症组终生及目前共患情感障碍、焦虑障碍、广泛焦虑障碍、注意缺陷多动障碍、对立违抗障碍、抽动障碍的比例高于低功能孤独症组（P均＜0.05）。高功能孤独症组精神科用药史、目前上学比例高于低功能孤独症组,自幼发育落后比例低于低功能孤独症组（P均＜0.05）。高功能孤独症组CARS得分低于低功能孤独症组,C-GAS得分高于低功能孤独症组（P均＜0.05）。结论 共患病在学龄期高功能及低功能孤独症儿童中均非常常见。高功能孤独症患儿较低功能孤独症患儿具有更多的情绪行为障碍、较轻的孤独症症状、更多的精神科用药史,总体功能优于低功能孤独症患儿     

Prévalence de l’autisme et autres troubles envahissants du développement : données des registres français de population. Générations 1995–2002

Aim and background

In France, prevalence data of pervasive developmental disorders in children are rare despite recently dedicated public health plans aimed to improve the knowledge and types of care of these disorders. Within this context, the two French childhood disabilities registers of Haute-Garonne and Isere counties have been asked to provide recent prevalence data on autism spectrum disorders.

Methods

These two population-based registers record all the cases of pervasive developmental disorders in children residing in covered counties in their eighth year of life, after parental approval. Data are actively collected from the medical records available in various data sources. The main data source is the “county house for people with disabilities” i.e. the local authority which determines the orientation for special education and the decision of special allocation for disabled children. Other data sources are “autism resource centres” and psychiatric hospitals. Diagnoses were coded according to the International Classification of Disease (ICD 10). For this analyze, diagnoses selected were typical and atypical autism (F84.0 and F84.1), Asperger disorder (F84.5), other pervasive developmental disorders (F84.8) and pervasive developmental disorders not otherwise specified (F84.9). The data presented here concerned children born between 1995 and 2002. Prevalence rates were calculated for 10 000 children living in their eighth year of life in each counties.

Results

The overall prevalence rate in the eighth year of life over the whole study period was 31.9 per 10,000 children in Haute-Garonne and 34.9 per 10,000 in Isere, with a significant increasing trend between 1995 and 2002 in Haute-Garonne county. The sex-ratio was 3.8 and 3.5 respectively in Haute-Garonne and Isere. In both counties, about half of the children had an associated intellectual deficiency and about one third if only severe impairment (defined by an IQ below 50) was considered. An epilepsy was more often present when an intellectual deficiency was associated.

Conclusion

Data from the two French registers were quite comparable and demonstrated that prevalence rates of pervasive developmental disorders in the eighth year of life were in the lower range of those published in the international literature.     

Extraction and Refinement Strategy for detection of autism in 18-month-olds: a guarantee of higher sensitivity and specificity in the process of mass screening

Background: For early detection of autism, it is difficult to maintain an efficient level of sensitivity and specificity based on observational data from a single screening. The Extraction and Refinement (E&R) Strategy utilizes a public children’s health surveillance program to produce maximum efficacy in early detection of autism. In the extraction stage, all cases at risk of childhood problems, including developmental abnormality, are identified; in the refinement stage, cases without problems are excluded, leaving only cases with conclusive diagnoses. Methods: The city of Yokohama, Japan, conducts a routine child health surveillance program for children at 18 months in which specialized public health nurses administer YACHT‐18 (Young Autism and other developmental disorders CHeckup Tool), a screening instrument to identify children at risk for developmental disorders. Children who screen positive undergo further observation, and those without disorders are subsequently excluded. To study the efficacy of early detection procedures for developmental disorders, including autism, 2,814 children born in 1988, examined at 18 months of age, and not already receiving treatment for diseases or disorders were selected. Results: In the extraction stage, 402 (14.3%) children were identified for follow‐up. In the refinement stage, 19 (.7%) of these were referred to the Yokohama Rehabilitation Center and diagnosed with developmental disorders. The extraction stage produced four false negatives, bringing total diagnoses of developmental disorders to 23 (.8%) – including 5 with autistic disorder and 9 with pervasive developmental disorder – not otherwise specified (PDDNOS). Sensitivity was 60% for autistic disorder and 82.6% for developmental disorders. Specificity for developmental disorders rose to 100% with the E&R Strategy. Picture cards used in YACHT‐18 provided a finer screen that excluded some false positive cases. Conclusions: An extraction and refinement methodology utilizing child health surveillance programs achieve high efficacy for early detection of autism.