Behaviour disorders in children with an intellectual disability

Behaviour disorders are frequent in children with an intellectual disability, regardless of the underlying etiology. They are often disabling, and can create problems in everyday life and can mask, or reveal, an organic or psychiatric illness. Such behaviours are often chronic and more than one may be present in the same individual. This is further complicated by the fact that parents often do not seek help for the problem, perhaps believing that it is due to the child’s disability and cannot be treated. The present review describes some general concepts dealing with the management of behaviour disorders commonly seen in children and youth with an intellectual disability, and gives a high level overview of behaviours commonly problematic in this patient population including sleep disturbances, agitated and aggressive behaviours, and self-injury behaviour. In general, while pharmacological treatment is possible, behavioural intervention is a more effective and better tolerated form of treatment.     

Epilepsy and associated psychopathology in young people with intellectual disability

OBJECTIVE: This study aimed to investigate the role of epilepsy in psychopathology among an epidemiological sample of young people with intellectual disability (ID). The study also compared behavioural and emotional problems in young people on medication to control their epilepsy with those not on medication, and young people with epilepsy who were having current seizure activity with those with no current seizure activity. METHODOLOGY: An epidemiological cohort of 392 participants, representative of the general Australian population of young people with ID, were used in the study. One hundred and fifteen individuals from this cohort were identified as suffering from epilepsy. The Developmental Behaviour Checklist was used to measure symptoms of behavioural and emotional disturbance. RESULTS: Results confirmed that young people with ID and epilepsy did not differ from controls without epilepsy on measures of psychopathology. Furthermore, those with epilepsy on medication had no difference in levels of problem behaviours than epileptics not on medication. CONCLUSIONS: The results suggest that epilepsy has little or no influence on problem behaviours for young people with ID. Our attempt to understand the pathogenesis of behaviour problems in persons with ID may be better directed towards understanding genetic mechanisms than epilepsy pathologies.     

智力障碍儿童的亚端粒拷贝数变异检测

目的应用多重连接探针扩增技术(MLPA)检测亚端粒拷贝数变异,探讨遗传性智力障碍(ID)的发病机制。方法收集68例G-显带染色体核型分析结果正常的ID患儿,通过MLPA P036筛查亚端粒拷贝数变异。结果 68例患儿中检出亚端粒拷贝数异常者7例(10%),均为缺失突变,其中1例患儿涉及2个亚端粒的缺失变异,另1例患儿涉及4个亚端粒的缺失变异。结论亚端粒拷贝数变异是遗传性ID的重要病因;MLPA可作为研究遗传性ID患儿发病机制的经济、有效的方法。     

Phenotype profiling of patients with intellectual disability and copy number variations

BackgroundNowadays the microarray technology allows whole-genome analysis with a high resolution and performance for the genetic diagnosis in any patient with intellectual disability or autism spectrum disorder. However in the immediate future, with the development of massive sequencing systems for application at clinical diagnosis, it will be necessary to have clinical criteria to guide studies.AimTo perform an exhaustive clinical definition of patients with pathogenic copy number variations in order to establish the clinical criteria most suggestive of this kind of genomic rearrangements.MethodWe designed and implemented a database to collect 190 different clinical variables (pregnancy, neonatal, facial dysmorphism, congenital anomalies, neurological features and family history) in a series of 246 patients, with developmental delay/intellectual disability. All cases were studied with array comparative genomic hybridization.ResultsWe have found a pathogenic genomic imbalance in 73 patients. Frequency analysis of all clinical variables showed that growth disorder, abnormalities of hands, low-set ears and hypertelorism are the more frequent features among patients with genomic rearrangements. However other clinical features, such as genital abnormalities and aggressiveness, are more specifically associated with pathogenic copy number variations in spite of their low frequencies in the overall series, yielding higher statistical significance values than other traits.ConclusionsThe genotype–phenotype comparison may be useful to set in the future the main clinical manifestations associated with deletions, duplications and unbalanced translocations. Theses analyses will improve the clinical indications and protocols to implement genomic arrays in the genetic study of patients with neurodevelopment disorders.     

微阵列比较基因组杂交技术对不明原因智力低下/生长发育迟缓患儿的分子诊断

目的　分析不明原因智力低下(ID)和(或)生长发育迟缓(DD)患儿潜在的致病性基因组不平衡, 及其与表型的相关性, 探讨高密度微阵列比较基因组杂交技术(array-CGH)在临床分子遗传学诊断中的应用价值。方法　采用array-CGH技术对16例ID/DD患儿进行全基因组扫描分析, 并用多重连接探针扩增技术(MLPA)对检出的基因组不平衡异位进行验证。结果　16例患儿高分辨G显带核型分析均无异常。6例(38%)患儿存在基因拷贝数异常(CNVs), 其中3例CNVs为正常多态性改变; 1例CNVs涉及4p16.3区域微缺失, 考虑为Wolf-Hirschhorn综合征; 1例CNVs涉及7q11.23区域微缺失, 考虑为Williams-Beuren 综合征; 另1例CNVs临床意义不明确, 包含2个重复突变, 该突变与智力低下、脑发育迟缓、特殊面容、隐睾、牙列不齐等有关, 证实该CNVs具有临床意义。结论 通过array-CGH技术对不明原因ID/DD患儿进行全基因组扫描, 可为部分患儿明确病因诊断。该技术作为一种高通量、快速的疾病研究手段, 在ID/DD的病因诊断中具有重要的临床意义。     

Developmental course of psychopathology in youths with and without intellectual disabilities

BACKGROUND: We aimed to describe similarities and differences in the developmental course of psychopathology between children with and without intellectual disabilities (ID). METHODS: Multilevel growth curve analysis was used to analyse the developmental course of psychopathology, using the Child Behavior Checklist (CBCL), in two longitudinal multiple-birth-cohort samples of 6- to 18-year-old children with ID (N = 978) and without ID (N = 2,047) using three repeated measurements across a 6-year period. RESULTS: Children with ID showed a higher level of problem behaviours across all ages compared to children without ID. A significant difference between the samples in the developmental courses was found for Aggressive Behaviour and Attention Problems, where children with ID showed a significantly larger decrease. Gender differences in the development of psychopathology were similar in both samples, except for Social Problems where males with ID showed a larger decrease in problem behaviour across time than females with ID and males and females without ID. CONCLUSIONS: Results indicate that children with ID continue to show a greater risk for psychopathology compared to typically developing children, although this higher risk is less pronounced at age 18 than it is at age 6 for Aggressive Behaviour. Contrary to our expectations, the developmental course of psychopathology in children with ID was quite similar from age 6 to 18 compared to children without ID. The normative developmental trajectories of psychopathology in children with ID, presented here, can serve as a yardstick against which development of childhood psychopathology can be detected as deviant.     

Psychopathology in children with intellectual disability

Recent advances are reviewed in understanding the heightened prevalence of psychopathology and maladaptive behavior among children with intellectual disability. Researchers have traditionally emphasized measurement and prevalence issues, using either psychiatric assessments or rating scales to identify the prevalence of various problems in children with intellectual disability. Yet the time is ripe to shift directions, and identify more precisely why children are at increased risk for psychopathology to begin with. Although several "biopsycho-social" hypotheses are reviewed, a particularly promising line of work links psychopathology to genetic intellectual disability syndromes. Psychiatric vulnerabilities in several syndromes are reviewed, as are the advantages of phenotypic work for understanding psychopathology among children with intellectual disability more generally.     

智力障碍的病因及诊断方法

智力障碍是儿童常见的神经系统疾病, 人群中发病率为1%~3%。由于多种遗传和环境因素参与其发病过程, 获得明确的病因学诊断是一项充满挑战的工作, 但其对评估患者预后、指导患者治疗及再生育具有重要的意义。该文总结了智力障碍的遗传学病因研究进展及临床常用遗传学诊断方法, 并介绍了最近美国儿科学会发布的智力障碍遗传诊断流程。     

Etiological yield of SNP microarrays in idiopathic intellectual disability

Intellectual disability (ID) has a prevalence of 3% and is classified according to its severity. An underlying etiology cannot be determined in 75–80% in mild ID, and in 20–50% of severe ID. After it has been shown that copy number variations involving short DNA segments may cause ID, genome-wide SNP microarrays are being used as a tool for detecting submicroscopic copy number changes and uniparental disomy. This study was performed to investigate the presence of copy number changes in patients with ID of unidentified etiology. Affymetrix^® 6.0 SNP microarray platform was used for analysis of 100 patients and their healthy parents, and data were evaluated using various databases and literature. Etiological diagnoses were made in 12 patients (12%). Homozygous deletion in NRXN1 gene and duplication in IL1RAPL1 gene were detected for the first time. Two separate patients had deletions in FOXP2 and UBE2A genes, respectively, for which only few patients have recently been reported. Interstitial and subtelomeric copy number changes were described in 6 patients, in whom routine cytogenetic tools revealed normal results. In one patient uniparental disomy type of Angelman syndrome was diagnosed. SNP microarrays constitute a screening test able to detect very small genomic changes, with a high etiological yield even in patients already evaluated using traditional cytogenetic tools, offer analysis for uniparental disomy and homozygosity, and thereby are helpful in finding novel disease-causing genes: for these reasons they should be considered as a first-tier genetic screening test in the evaluation of patients with ID and autism.     

Prevalence and outcomes of renal transplantation in children with intellectual disability

To describe the prevalence and outcomes of renal transplantation in children with ID we performed a retrospective cohort analysis of all children receiving a first kidney‐alone transplant in the UNOS dataset from 2008 to 2011. Recipients with definite, probable, and without ID were compared using chi‐square tests. Kaplan–Meier curves were constructed for patient and graft survival. Cox proportional hazard models were used to estimate the association between ID and graft failure and patient survival. Over the study period, 332 children with definite (117) or probable (215) ID underwent first renal transplant, accounting for 16% of all first pediatric renal transplants (n = 2076). Children with definite ID were not significantly different from children without ID with respect to sex, ethnicity, or prevalence of acute rejection. ID was associated with increased likelihood of deceased donor source. ID was not significantly associated with decreased graft or patient survival. In this first large‐scale study, up to 16% of first pediatric renal transplants were performed in children with ID. Short‐term graft and patient survival after transplant were equivalent between children with and without ID. Further research is needed to examine long‐term outcomes of transplant in this population.     

6~18岁智力障碍人群的孤独症谱系障碍样症状分析

目的 了解智力障碍（ID）人群的孤独症谱系障碍（ASD）样症状的发生情况。方法 选取2017年1~6月就读于上海市某特殊学校的6~18岁ASD人群和ID人群,以及同期在上海市某普通学校就读的同年龄段普通（TD）人群,由父母或其他监护人填写社交反应量表（SRS）,分别对其进行ASD样症状评估。结果 共纳入69例ASD、74例ID和177例TD研究对象。ID组SRS量表检查阳性率（47.3%）显著高于TD组（1.7%）（P < 0.001）,低于ASD组（87.0%）（P < 0.001）。ASD组、ID组和TD组SRS量表总分分别为114±26、80±24、38±19分,其中ID组SRS量表总分显著高于TD组得分（P < 0.05）,以社交认知维度差异最为显著（Cohen's d值为2.00）。轻-中度ID亚组和重-极重度ID亚组的SRS总分及各维度得分差异无统计学意义（P > 0.05）,且SRS得分与IQ之间无明显相关性（P > 0.05）。结论 6~18岁ID人群较普通人群存在更显著的ASD样症状,应对ID人群尽早进行ASD筛查并给予干预。     

Psychological and school functioning of Latino siblings of children with intellectual disability

Background: Siblings of children with disabilities are at risk for internalizing psychological disorders; however, little is known about how culture influences this effect. This study examined the psychological and school functioning of Latino siblings of children with intellectual disability (ID). Methods: Participants were 100 Latino (L) and nonLatino (NL) siblings (8–15 years) of children with ID (50 LID, 50 NLID) and 100 Latino and nonLatino control siblings (50 LC, 50 NLC). Siblings, parents, and teachers completed standard questionnaires regarding sibling emotional and behavioral functioning; sibling school report cards were obtained. Analyses of variance were conducted, controlling for parent age and family income; planned contrasts compared LID siblings to the other sibling groups. Results: LID siblings reported significantly more internalizing (t(1) = 2.41, p < .05) and emotional t(1) = 3.06, p < .05) symptoms, poorer awareness of (t(1) = 2.26, p < .01) and greater reluctance to express (t(1) = 3.12, p < .01) their emotions, and more problems in personal adjustment and relationships with parents (t(1) = ?2.50, p < .05). Significantly higher percentages of LID siblings scored in the at‐risk or clinical range for internalizing and emotional symptoms, and were more likely to score above the clinical cut‐off for separation anxiety disorder and to endorse global impairment. LID siblings experienced more school absences and lower academic performance. There were no group differences in externalizing behavior problems, somatic symptoms, or teacher‐reported internalizing symptoms. Conclusions: Latino siblings of children with ID are at greater risk for internalizing psychological disorders and greater impairment in personal and school functioning. Results are discussed in terms of their sociocultural significance and clinical implications.     

High prevalence of cardio-metabolic risk factors among adolescents with intellectual disability

Adults with intellectual disabilities (IDs) have poor lifestyle-related health compared with the general population. Our aim was to study whether such differences are present already in adolescents.
Aim: To compare the prevalence and severity of cardio-metabolic risk factors and cardio-vascular fitness in adolescents with and without IDs.
Methods: Intellectual disability (ID) students (n = 66) and non-intellectual disability (non-ID) students from practical (non-ID-p) (n = 34) and theoretical (non-ID-t) (n = 56) programmes were recruited from three upper secondary schools. Anthropometric data, blood pressure, body composition, fasting-insulin, fasting-glucose, fasting-lipids and cardio-vascular fitness were measured.
Results: Participants with and without ID differed significantly in the prevalence of cardio-metabolic risk factors with participants with ID having a higher percentage of total fat mass, wider waist circumferences (WCs), lower levels of fat-free mass (FFM), lower bone mineral density (BMD) and higher insulin and homeostasis model assessment of insulin resistance (HOMA) levels and poorer cardio-vascular fitness. The healthiest levels were found in the non-ID-t group compared to the group with ID and the group with non-ID-p in between.
Conclusion: The prevalence of cardio-metabolic risk factors and poor cardio-vascular fitness was found to be high in this young population with intellectual disabilities. Measures should be taken to improve the health messages directed towards children and adolescents with intellectual disabilities.     

School performance and intellectual outcome in adolescents with phenylketonuria

In a retrospective study, 34 treated adolescents with phenylketonuria and their relatives were tested with scale 2 of the Culture Fair Intelligence Test (CFT 20) and self-developed questionnaire concerning their development in school. The patients also filled in the Anxiety Questionnaire for Children. With an IQ of 93.6, the patients reached a normal mean intellectual performance but this was significantly below the mean IQ of the general population (100, p < 0.01), the IQ of their mothers (98.2, p < 0.05), their fathers (105.4, p<0.05) and their siblings (110.3, p<0.05 ). The patients' IQs correlated significantly with the IQs of their mothers, the socio-economic status of their families, the quality of dietary control since birth and the serum phenylalanine concentration at the moment of testing. With respect to age at which the patients started school, type of school attended and number of school years which had to be repeated, there were no significant differences between the patients and their siblings. The patients did not display a markedly higher degree of general anxiety, nervousness at examination time or a greater reluctance to attend school.     

Practitioner review: stress intervention for parents of children with intellectual disabilities

BACKGROUND: Parents of children with intellectual disabilities are at increased risk for stress and other mental health problems. The purpose of the present review is to consider the evidence base for psychological intervention to remediate stress in these parents. METHODS: A selective review of interventions designed to reduce stress in parents of children with intellectual disabilities, with a focus on group interventions that incorporate various cognitive behavioural techniques. RESULTS: Research evidence suggests that standard service models (e.g., respite care, case management) probably help to reduce parental stress. The strongest evidence base is for cognitive behavioural group interventions, especially for the reduction of stress in mothers. Some data also indicate the potential value of parent-led support networks. CONCLUSIONS: More research and clinical development are needed to establish a firmer evidence base for stress interventions with parents of children with intellectual disabilities. There are also a number of potential practical implications of reducing parental stress for maximising the efficacy of general parent training interventions and also behavioural programmes for children's challenging behaviours.