Difference in age at regression in children with autism with and without Down syndrome

OBJECTIVE: Autism occurs more frequently in individuals with Down syndrome than it does in the general population. Among children with autism and Down syndrome, regression is reported to occur in up to 50%. The aim of this study was to characterize and compare regression in children with autism with and without Down syndrome. METHODS: In this case-control study, children with Down syndrome and autism characterized by a history of developmental regression (n = 12) were compared to children with autism with regression who did not have Down syndrome, matched for chronologic age and gender. Comparisons were made on age at acquisition of language and age at loss of language and other skills as measured by the Autism Diagnostic Interview-Revised (ADI-R). RESULTS: The mean age at acquisition of meaningful use of single words was 40.6 months (SD = 38.0) in children with Down syndrome and autism compared to 14.9 months (SD = 8.5) in children with autism without Down syndrome (p = .005). The mean age at language loss in children with autism with Down syndrome was 61.8 months (SD = 22.9) compared to 19.7 months (SD = 5.8) for those with autism without Down syndrome (p = .01). The mean age at other skill loss was 46.2 months (SD = 19.1) and 19.5 months (SD = 5.6), respectively (p = .006). CONCLUSIONS: When regression occurs in children with autism and Down syndrome it is, on average, much later than is typically seen in children with autism without Down syndrome.     

Behavior in children with Down syndrome

Objective  To highlight the differences in behaviors in children with diagnosis of down syndrome. Method  Eight children with Down syndrome who displayed autistic features were compared with eight Down syndrome children without autistic features. These children were randomly selected and were matched for age and level of retardation. Standardized Psychological tests were administered to tap the behavioral differences. Mann-Whitney U test was used for significance of difference between both the groups. Results  Down syndrome children without Autism Spectrum Disorder had better communication and socialization skills than children with Down syndrome with Autism Spectrum Disorder. Down syndrome children with Autism Spectrum Disorder displayed more restricted repetitive and stereotyped patterns of behaviors, interests and activities. Conclusion  Our findings indicate that Autism Spectrum Disorder manifests as a distinct behavioral phenomenon in Down syndrome. Hence it is important for professionals to consider the possibility of a dual diagnosis which will entitle the child to a more specialized and effective educational and intervention services.     

Bioelectrical impedance for measuring percentage body fat in young persons with Down syndrome: validation with dual‐energy absorptiometry

Aim: Children with Down syndrome have an increased prevalence of obesity, although there is little work describing body composition in this population. The aims of this study were to accurately measure body fat in children with Down syndrome and to identify which existing algorithm best predicts percentage body fat in this population. Methods: Seventy children with Down syndrome had anthropometric, bioelectrical impedance analysis (BIA) and dual‐energy X‐ray absorptiometry (DXA) data collected to calculate percentage body fat (PBF). Pearson correlations were carried out to assess the relationships of various methods for measuring body fat and Bland–Altman plots to assess systematic error. Results: Mean PBF was 30.5% for girls and 22.5% for boys. A total of 38% of girls and 23% of boys were obese according to international criteria. PBF as determined by DXA correlated well with PBF by BIA in both girls and boys (r = 0.91 and 0.89, respectively, p < 0.001). Conclusion: There are high rates of obesity in children with Down syndrome. BIA can be used to accurately determine adiposity in this population. We recommend the use of the Schaeffer algorithm for calculation of PBF in children with Down syndrome.     

Psychosocial adjustment in siblings of children with autism

BACKGROUND: This study investigated psychosocial adjustment in siblings of children with autism compared to siblings of children with Down syndrome and siblings of normally developing children. In addition, the relationships between feelings of loneliness, social support and psychosocial adjustment, and the influence of gender and family size on psychological adjustment were examined. METHODS: Ninety siblings (30 per group) between the ages of 8 and 18 and one parent of each child participated in this study. RESULTS: Results indicated that siblings of children with autism, as well as comparison siblings, were well adjusted and reported low levels of loneliness. Siblings of children with autism also reported that they received high levels of social support in their lives. CONCLUSIONS: Large family size appears to facilitate healthy adjustment in siblings of children with autism.     

Autisme du nourrisson : quoi de neuf dans le diagnostic et l'accompagnement ?

The field of knowledge on autism has deeply changed within a decade. We know more about the different kinds of pervasive developmental disorders, on their incidence, on the clinical aspects of onset of autism, on the possibility of early detection, as soon as 18 months of age, on the frequency of neurological and genetic disorders which may be associated with autism, and on the necessity of an early intervention. New media, as video, are useful to enhance assessment and therapeutic follow-up. Research allow for a therapeutic follow-up that goes further than the splitting between educative and psychodynamic trends of thoughts. However, prognosis in autism is still a difficult issue, and therapeutic efficiency is still globally low. This paper is not a literature review on pervasive disorders in general or particularly in autism, but aims at highlighting some new aspects which may be of interest for both clinicians and researchers on these several issues, about children up to 3 years of age.     

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.     

应用荧光原位杂交法检测口腔黏膜脱落细胞诊断唐氏综合征

目的：目前,临床应用荧光原位杂交（FISH）法诊断唐氏综合征多采用血液及皮肤活检组织,属于有创检查。该研究探讨应用FISH方法检测口腔黏膜细胞（无创取材）对唐氏综合征的诊断价值。方法：应用FISH方法对2010年3月至2011年3月16例可疑唐氏综合征患儿外周血及口腔黏膜脱落细胞进行检测分析;同时进行外周血淋巴细胞染色体核型分析。结果：FISH法检测外周血及口腔黏膜脱落细胞标本,显示14例为21-三体综合征,2例21号染色体数目正常,结果与外周血染色体核型分析结果一致。结论：应用FISH方法对口腔黏膜脱落细胞标本进行检测可为唐氏综合征的准确、无创性诊断提供新的检测途径。     

Down syndrome: orthopedic issues

PURPOSE OF REVIEW: The purpose of this review is to update the role of the orthopedic surgeon in the management of Down syndrome as these patients are living longer and participating in sporting activities. RECENT FINDINGS: Approximately 20% of all patients with Down syndrome experience orthopedic problems. Upper cervical spine instability has the most potential for morbidity and, consequently, requires close monitoring. Other conditions such as scoliosis, hip instability, patellar instability and foot problems can cause disability if left untreated. In some of these conditions, early diagnosis can prevent severe disability. SUMMARY: Surgical intervention in children with Down syndrome has a high risk of complications, particularly infection and wound healing problems. Careful anesthetic airway management is needed because of the associated risk of cervical spine instability.     

Down syndrome and breastfeeding

AIM: The aim of the study was to investigate the frequency of breastfeeding among children with Down syndrome. METHODS: The mothers of 560 children with Down syndrome attending four university hospitals in Italy were interviewed and the neonatal clinical records retrieved. Information was collected on the type of infant feeding and on why some mothers had not breastfed their children. Two groups of healthy children whose feeding habits had been previously investigated were recruited as control subjects (1601 and 714, respectively). A paediatrician in each hospital was interviewed about the neonatal admission policy of children with Down syndrome. RESULTS: Among the 560 Down children, 246 (44%) were admitted to the neonatal unit. Compared with the two control groups, children with Down syndrome were significantly more frequently bottle-fed (57% vs 15% and 24%, respectively, odds ratio 7.5, 95% CI 6.0-9.4 and 4.2, 95% CI 3.3-5.4. respectively). Only 30% of infants admitted to the neonatal unit were breastfed. The main reasons reported by the mothers for not having breastfed were infants' illness in infants who had been admitted to the neonatal unit and frustration or depression, perceived milk insufficiency and difficulty with suckling for those babies who had not been admitted to the unit. The paediatricians reported that the admission of a baby with Down syndrome to the neonatal unit could sometimes take place not for medical reasons, but for diagnostic work-up or for a more appropriate diagnosis and to maintain communication with the family. CONCLUSIONS: Down syndrome babies are less frequently breastfed compared with healthy children. Support in breastfeeding should become a relevant point of health supervision for children with Down syndrome.     

Down syndrome and coeliac disease: five new cases with a review of the literature

We report five new patients with coeliac disease and Down syndrome and review the 11 cases previously reported in the literature. In 14 of these 16 patients diarrhoea was the presenting symptom and in 2 failure to thrive in combination with anaemia. The frequency of coeliac disease in children with Down syndrome was calculated as being 43 times greater than in children without Down syndrome. Delay between first symptoms and diagnosis in patients with combined coeliac disease and Down syndrome was 2.5 years, while in the other children with coeliac disease it was only 8 months. This distinctive difference could be caused by an underestimation of the seriousness of gastro-intestinal complaints in patients with Down syndrome. It is stressed that coeliac disease should be strongly considered in all children with Down syndrome and either persistent diarrhoea or failure to thrive.     

Syndrome de Moyamoya et trisomie 21 : à propos de 2 cas

Moyamoya syndrome has rarely been reported in association with Down syndrome. We report on 2 cases in 3-year-old and 6-year-old female children with Down syndrome, who presented with neurological deficit. Imaging (magnetic-resonance angiography and digital-subtraction angiography) revealed the classical Moyamoya pattern. The neurological deficits persisted in both cases. One patient has developed epilepsy.     

Technical report: the pediatrician's role in the diagnosis and management of autistic spectrum disorder in children

Autism and its milder variants are not rare. Most pediatricians will have the opportunity to provide a medical home for a child with autism. This technical report serves to complement and expand on the information in the accompanying policy statement to increase the pediatrician's fund of knowledge and comfort level in caring for children with autism. In so doing, it is anticipated that earlier diagnosis and referral for appropriate intervention will be possible and that this will, in turn, have a positive effect on long-term outcomes for children with autism and their families.     

Down综合征患儿睡眠特征多导睡眠图的回顾性研究

目的 探讨Down综合征患儿的睡眠结构和基本睡眠参数的特点。方法 选取10例Down综合征患儿为Down组，采用染色体核型检查进行Down综合征的诊断，其中男7例，女3例，年龄中位数8岁2个月；选取声带小结患儿14例及突发性耳聋6例患儿为对照组，其中男12例，女8例，年龄中位数8岁9个月。两组患儿均接受整夜多导睡眠图监测，按中华医学会耳鼻咽喉科学分会制定的儿童阻塞性睡眠呼吸暂停低通气综合征（OSAHS）诊疗指南（草案）中的标准进行呼吸事件的定义和OSAHS的诊断，阻塞性呼吸暂停指数（OAI）每小时≤1次或呼吸暂停低通气指数(AHI) 每小时≤5次，最低血氧饱和度(LSaO2)≥0.92可以排除OSAHS。应用Mann-Whitney U和精确概率检验，比较Down组和对照组的睡眠结构，并进行睡眠期LSaO2、OAI、AHI、脑电醒觉反应指数及睡眠期肢体运动事件指数的比较。结果 ①两组间在年龄、性别和体重指数等差异无统计学意义（P＞0.05）；②Down组和对照组比较，快动眼睡眠比例减少，且差异有显著统计学意义（Z=-2.6，P= 0.009）；③睡眠期LSaO2较对照组显著下降（P＜0.05），OAI、AHI及睡眠期肢体运动事件指数Down组较对照组显著升高（P＜0.05）；④10例Down综合征患儿中有6例符合OSAHS诊断，6例中有5例为男性。结论 Down综合征患儿存在睡眠呼吸紊乱，应使用多导睡眠检测的方法尽早发现睡眠呼吸紊乱的问题。     

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.     

Systematic review of the effect of therapeutic dietary supplements and drugs on cognitive function in subjects with Down syndrome.

The objective was to evaluate the effects of therapeutic dietary supplements and drugs on cognitive function in subjects with Down syndrome. The study design was a systematic review of randomized controlled trials of dietary supplements and/or drugs reporting any assessment of cognitive function in subjects with Down syndrome. Eleven trials were identified with 373 randomized participants. None of the trials reported cognitive enhancing effect in subjects with Down syndrome. Meta-analysis was not conducted due to the heterogeneous nature of the population, interventions and outcome measures used. Overall, the quality of the trials was poor with few subjects and generally inadequate allocation concealment of the treatments given. This comprehensive systematic review provides no positive evidence that any combination of drugs, vitamins and minerals enhance either cognitive function or psychomotor development in people with Down syndrome. However, because of the small number of subjects involved and the overall unsatisfactory quality of the trials, an effect cannot be excluded at this point. At present there is no justification for the use of such regimes outside the context of large well designed trials. Parents of children with Down syndrome should be actively discouraged from giving these 'miracle drugs' to their children.     

Autism Spectrum Disorders at 20 and 42 Months of Age: Stability of Clinical and ADI-R Diagnosis

The association between, and stability of, clinical diagnosis and diagnosis derived from the Autism Diagnostic Interview-Revised (ADI-R; Lord, Rutter, & Le Couteur, 1994) was examined in a sample of prospectively identified children with childhood autism and other pervasive developmental disorders assessed at the age of 20 months and 42 months. Clinical diagnosis of autism was stable, with all children diagnosed with childhood autism at age 20 months receiving a diagnosis of childhood autism or a related pervasive developmental disorder (PDD) at age 42 months. Clinical diagnosis of childhood autism was also reasonably sensitive, with all children who went on to receive a clinical diagnosis of childhood autism at 42 months being identified as having autism or PDD at 20 months. However, clinical diagnosis for PDD and Asperger's syndrome lacked sensitivity at 20 months, with several children who subsequently received these diagnoses at 42 months receiving diagnoses of language disorder or general developmental delay, as well as in two cases being considered clinically normal, at the earlier timepoint. The ADI-R was found to have good specificity but poor sensitivity at detecting childhood autism at 20 months; however, the stability of diagnosis from 20 to 42 months was good. In addition, the ADI-R at age 20 months was not sensitive to the detection of related PDDs or Asperger's syndrome. The continuity and discontinuity between behavioural abnormalities identified at both timepoints in the three domains of impairment in autism was examined, both in children who met final clinical criteria for an autistic spectrum disorder, and for children with language disorder who did not, as well as for a small sample of typically developing children.     

Immunological patterns in young children with Down syndrome: is there a temporal trend?

Down syndrome is associated with an increased susceptibility to infections due to a deficiency of both specific and nonspecific immunity. AIM: The aim of the study was to analyze the temporal trends, if any, of some variables related to the immunological status of children affected by Down syndrome. METHODS: Heparinized blood samples were obtained by venipuncture in 30 children with Down syndrome, who were regularly followed in our department and analyzed for hematologic values, lymphocyte subpopulations, immunoglobulin dosage and zinc level. Results were compared with those of the normal population. RESULTS: In the first 5 years of life, we observed a progressive decrease in the medium values of lymphocytes, CD4(+) and plasma zinc levels, and an increase in CD8(+), immunoglobulin A, immunoglobulin G, immunoglobulin M and natural killer, but generally without exceeding the interval of normality. CONCLUSIONS: In Down syndrome children, the immune cellular status is similar to the normal population as far as white blood cell, lymphocyte, CD4(+), CD8(+), natural killer and immunoglobulins are concerned. Plasma level of zinc is normal from birth until 5 years but with a temporal trend of progressive reduction. This observation supports the hypothesis that a pharmacological supplementation may be necessary in Down syndrome children only after 5 years of age.     

Continuity and change from early childhood to adolescence in autism

BACKGROUND: This longitudinal study of 48 children diagnosed with autism at 2-5 years of age was designed to test the hypothesis that diagnosis would remain stable for most of the sample but that there would be improvements in symptom severity, adaptive behavior, and emotional responsiveness in adolescence. METHODS: A sample of children with autism assessed in both early and middle childhood were observed in late adolescence with the Autism Diagnostic Observation Scale (ADOS) and their parents were administered the Autism Diagnostic Interview-Revised (ADI-R) and the Vineland Adaptive Behavior Scale. RESULTS: All but 2 adolescents (46 of 48) met lifetime criteria for autism according to the ADI-R, and all but 4 adolescents (40 of 44) met criteria for autism spectrum disorder on the ADOS. In contrast to the continuity in diagnosis, parents described improvements in social interactions, repetitive/stereotyped behaviors, adaptive behaviors, and emotional responsiveness to others' distress in adolescence compared to middle childhood. High-functioning adolescents with autism showed more improvement in these domains than low-functioning adolescents with autism. The extent to which the adolescents were observed to be socially engaged with their peers in school in middle childhood predicted adaptive behavior skills even when intelligence level was statistically constrained. CONCLUSIONS: The developmental trajectory of children with autism appears to show both continuity and change. In this sample, most individuals continued to be diagnosed in the autism spectrum but parents reported improvements in adolescence. The results suggest that social involvement with peers improves adaptive behavior skills, and this argues for focusing intervention programs in this area. In addition, it is clear that high-functioning adolescents improve more than low-functioning individuals not only in cognitive abilities but also in social interaction skills. Thus, any early intervention that impacts the cognitive abilities of young children with autism is likely to have a parallel influence on their social skills as they mature into late adolescence and early adulthood.