Identifying latent subgroups of children with developmental delay using Bayesian sequential updating and Dirichlet process mixture modelling.

Identifying children who are at-risk for developmental delay, so that these children can have access to interventions as early as possible, is an important and challenging problem in developmental research. This research aimed to identify latent subgroups of children with developmental delay, by modelling and clustering developmental milestones. The main objectives were to (a) create a developmental profile for each child by modelling milestone achievements, from birth to three years of age, across multiple domains of development, and (b) cluster the profiles to identify groups of children who show similar deviations from typical development. The ensemble methodology used in this research consisted of three components: (1) Bayesian sequential updating was used to model the achievement of milestones, which allows for updated predictions of development to be made in real time; (2) a measure was created that indicated how far away each child deviated from typical development for each functional domain, by calculating the area between each child's obtained sequence of posterior means and a sequence of posterior means representing typical development; and (3) Dirichlet process mixture modelling was used to cluster the obtained areas. The data used were 348 binary developmental milestone measurements, collected from birth to three years of age, from a small community sample of young children (N = 79). The model identified nine latent groups of children with similar features, ranging from no delays in all functional domains, to large delays in all domains. The performance of the Dirichlet process mixture model was validated with two simulation studies.

Testing single/combined clinical categories on 5110 Italian patients with developmental phenotypes to improve array-based detection rate.

BACKGROUND: Chromosomal microarray analysis (CMA) is nowadays widely used in the diagnostic path of patients with clinical phenotypes. However, there is no ascertained evidence to date on how to assemble single/combined clinical categories of developmental phenotypic findings to improve the array-based detection rate. METHODS: The Italian Society of Human Genetics coordinated a retrospective study which included CMA results of 5,110 Italian patients referred to 17 genetics laboratories for variable combined clinical phenotypes. RESULTS: Non-polymorphic copy number variants (CNVs) were identified in 1512 patients (30%) and 615 (32%) present in 552 patients (11%) were classified as pathogenic. CNVs were analysed according to type, size, inheritance pattern, distribution among chromosomes, and association to known syndromes. In addition, the evaluation of the detection rate of clinical subgroups of patients allowed to associate dysmorphisms and/or congenital malformations combined with any other single clinical sign to an increased detection rate, whereas non-syndromic neurodevelopmental signs and non-syndromic congenital malformations to a decreased detection rate. CONCLUSIONS: Our retrospective study resulted in confirming the high detection rate of CMA and indicated new clinical markers useful to optimize their inclusion in the diagnostic and rehabilitative path of patients with developmental phenotypes.

Cardiac manifestations and gene mutations of patients with RASopathies in Taiwan.

RASopathies are developmental diseases caused by mutations in rat sarcoma-mitogen-activated protein kinase pathway genes. These disorders, such as Noonan syndrome (NS) and NS-related disorders (NSRD), including cardio-facio-cutaneous (CFC) syndrome, Costello syndrome (CS), and NS with multiple lentigines (NSML; also known as LEOPARD syndrome), have a similar systemic phenotype. A wide spectrum of congenital heart disease and hypertrophic cardiomyopathy (HCMP) can exhibit major associated characteristics. A retrospective study was conducted at the Mackay Memorial Hospital, National Taiwan University Hospital, Buddhist Tzu-Chi General Hospital, Chang-Gung Memorial Hospital, Taichung Veterans General Hospital, and Chung Shan Medical University Hospital from January 2007 to December 2018. We reviewed the clinical records of 76 patients with a confirmed molecular diagnosis of RASopathies, including NS, CS, CFC syndrome, and NSML. We evaluated the demographic data and medical records with clinical phenotypes of cardiac structural anomalies using cross-sectional and color Doppler echocardiography, electrocardiographic findings, and follow-up data. A total of 47 (61.8%) patients had cardiac abnormalities. The prevalence of cardiac lesions according to each syndrome was 62.7, 50.0, 60.0, and 66.7% in patients with NS, CFC syndrome, CS, and NSML, respectively. An atrial septal defect was usually combined with other cardiac abnormalities, such as pulmonary stenosis (PS), HCMP, ventricular septal defect, or patent ductus arteriosus. Patients with NS most commonly showed PS. In patients with NSRD and cardiac abnormalities, HCMP (29.4%) was the most commonly observed cardiac lesion. PTPN11 was also the most frequently detected mutation in patients with NS and NSRD. Cardiac abnormalities were the most common symptoms observed in patients with RASopathies at the time of their first hospital visit. Performing precise analyses of genotype-cardiac phenotype correlations in a larger cohort will help us accurately diagnose RASopathy as soon as possible.

The contemporary view of intellectual and developmental disabilities: implications for psychologists / La visión contemporánea de las discapacidades intelectuales y del desarrollo: implicaciones para psicólogos

Background: The field of intellectual and developmental disabilities (IDD) is currently experiencing a significant transformation that encompasses an integrated approach, especially regarding shared aspects such as a focus on the human and legal rights, the eligibility for services and supports, and an emphasis on individualized supports provided within inclusive community-based environments. Accompanying this transformation is the increased need of precision in both the operational definitions of IDD-related constructs, and the terminology used to describe the respective construct. Method: the specialized literature was revised, and previous works on the subject by the authors were updated. Results: This article provides psychologists with the current definition of intellectual disability, operational definitions of intellectual disability and developmental disabilities constructs and associated terminology, and the parameters of an integrated approach to disability. Conclusions: Implications for psychologists who are involved in diagnosis, classification, and planning supports for persons with intellectual or developmental disability are discussed

Antecedentes: el campo de la discapacidad intelectual y del desarrollo (DID) experimenta en la actualidad una significativa transformación que implica un enfoque integrado, especialmente en lo que se refiere a aspectos compartidos como el enfoque en los derechos humanos y legales, la elegibilidad para recibir servicios y apoyos, y el énfasis en los apoyos individualizados proporcionados en entornos comunitarios inclusivos. Esta transformación se acompaña de una creciente necesidad de precisión en cuanto las definiciones operativas de los constructos relacionados con la DID y la terminología utilizada para describir cada uno de ellos. Método: se ha revisado la literatura especializada y se han actualizado los trabajos previos de los autores sobre el tema. Resultados: este artículo proporciona a los psicólogos la definición actual de la discapacidad intelectual, las definiciones operativas de los constructos de discapacidad intelectual y discapacidades del desarrollo, así como de la terminología asociada, y los parámetros de un enfoque integrado de la discapacidad. Conclusiones: se discuten las implicaciones para los psicólogos involucrados en el diagnóstico, la clasificación y la planificación de apoyos a personas con discapacidad intelectual o del desarrollo

The contemporary view of intellectual and developmental disabilities: Implications for psychologists.

BACKGROUND: The field of intellectual and developmental disabilities (IDD) is currently experiencing a significant transformation that encompasses an integrated approach, especially regarding shared aspects such as a focus on the human and legal rights, the eligibility for services and supports, and an emphasis on individualized supports provided within inclusive community-based environments. Accompanying this transformation is the increased need of precision in both the operational definitions of IDD-related constructs, and the terminology used to describe the respective construct. METHOD: the specialized literature was revised, and previous works on the subject by the authors were updated. RESULTS: This article provides psychologists with the current definition of intellectual disability, operational definitions of intellectual disability and developmental disabilities constructs and associated terminology, and the parameters of an integrated approach to disability. CONCLUSIONS: Implications for psychologists who are involved in diagnosis, classification, and planning supports for persons with intellectual or developmental disability are discussed.

Does ICD-11 improve the epidemiological and nosological purposes of mental, behavioral and developmental disorders? / ¿Mejora la CIE-11 los propósitos epidemiológicos y nosológicos de los Trastornos mentales, del comportamiento y del desarrollo?

Editorial of vol 31(3).

Editorial del vol 31(3).

Refining the Phenotype of Recurrent Rearrangements of Chromosome 16.

Chromosome 16 is one of the most gene-rich chromosomes of our genome, and 10% of its sequence consists of segmental duplications, which give instability and predisposition to rearrangement by the recurrent mechanism of non-allelic homologous recombination. Microarray technologies have allowed for the analysis of copy number variations (CNVs) that can contribute to the risk of developing complex diseases. By array comparative genomic hybridization (CGH) screening of 1476 patients, we detected 27 cases with CNVs on chromosome 16. We identified four smallest regions of overlapping (SROs): one at 16p13.11 was found in seven patients; one at 16p12.2 was found in four patients; two close SROs at 16p11.2 were found in twelve patients; finally, six patients were found with atypical rearrangements. Although phenotypic variability was observed, we identified a male bias for Childhood Apraxia of Speech associated to 16p11.2 microdeletions. We also reported an elevated frequency of second-site genomic alterations, supporting the model of the second hit to explain the clinical variability associated with CNV syndromes. Our goal was to contribute to the building of a chromosome 16 disease-map based on disease susceptibility regions. The role of the CNVs of chromosome 16 was increasingly made clear in the determination of developmental delay. We also found that in some cases a second-site CNV could explain the phenotypic heterogeneity by a simple additive effect or a pejorative synergistic effect.

¿Mejora la CIE-11 los propósitos epidemiológicos y nosológicos de los Trastornos mentales, del comportamiento y del desarrollo? / Does ICD-11 improve the epidemiological and nosological purposes of mental, behavioral and developmental disorders?

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Nablus syndrome: Easy to diagnose yet difficult to solve.

Nablus syndrome was first described by the late Ahmad Teebi in 2000, and 13 individuals have been reported to date. Nablus syndrome can be clinically diagnosed based on striking facial features, including tight glistening skin with reduced facial expression, blepharophimosis, telecanthus, bulky nasal tip, abnormal external ear architecture, upswept frontal hairline, and sparse eyebrows. However, the precise genetic etiology for this rare condition remains elusive. Comparative microarray analyses of individuals with Nablus syndrome (including two mother-son pairs) reveal an overlapping 8q22.1 microdeletion, with a minimal critical region of 1.84 Mb (94.43-96.27 Mb). Whereas this deletion is present in all affected individuals, 13 individuals without Nablus syndrome (including two mother-child pairs) also have the 8q22.1 microdeletion that partially or fully overlaps the minimal critical region. Thus, the 8q22.1 microdeletion is necessary but not sufficient to cause the clinical features characteristic of Nablus syndrome. We discuss possible explanations for Nablus syndrome, including one-locus, two-locus, epigenetic, and environmental mechanisms. We performed exome sequencing for five individuals with Nablus syndrome. Although we failed to identify any deleterious rare coding variants in the critical region that were shared between individuals, we did identify one common SNP in an intronic region that was shared. Clearly, unraveling the genetic mechanism(s) of Nablus syndrome will require additional investigation, including genomic and RNA sequencing of a larger cohort of affected individuals. If successful, it will provide important insights into fundamental concepts such as variable expressivity, incomplete penetrance, and complex disease relevant to both Mendelian and non-Mendelian disorders.

Prediction of postnatal developmental disabilities using the antenatal fetal neurodevelopmental test: KANET assessment.

Objective To assess the usefulness of the antenatal fetal neurodevelopmental test for the prediction of postnatal developmental disabilities. Methods Fetal behavior was assessed with Kurjak's antenatal neurodevelopmental test (KANET) using four-dimensional ultrasound between 28 and 38 weeks of gestation. A score range of 0-5 was characterized as abnormal, from 6 to 9 was considered borderline, and 10-16 was normal. After birth, follow-up was conducted for at least 2 years in all fetuses. Results There were 337 normal (95.47%) and 16 borderline (4.53%) cases among the 353 cases studied, whereas there was no abnormal case. Five cases with postnatal developmental disabilities (one case of Werdig-Hoffmann disease diagnosed just after delivery, one case of autism spectrum disorder diagnosed at 24 months, one case of Ullrich congenital muscular dystrophy diagnosed at 9 months and two cases of developmental disorders diagnosed at age 3 and 18 months) were noted among the 337 normal cases (1.48%), whereas three cases with developmental disabilities (one case of motor development delay diagnosed at 6 months, one case of Duchenne muscular dystrophy diagnosed at 18 months and one case of autism spectrum disorder diagnosed at age 30 months) were found among the 16 borderline cases (18.75%). There was a significant difference in the prevalence of postnatal developmental disabilities between the normal and borderline KANET groups (P<0.001). Conclusion Our results suggest that the KANET assessment may be a useful diagnostic modality for the prediction of postnatal developmental disabilities.

The epileptic encephalopathy jungle - from Dr West to the concepts of aetiology-related and developmental encephalopathies.

PURPOSE OF REVIEW: We aim to further disentangle the jungle of terminology of epileptic encephalopathy and provide some insights into the current understanding about the aetiology and pathophysiology of this process. We cover also the key features of epilepsy syndromes of infancy and childhood which are considered at high risk of developing an epileptic encephalopathy. RECENT FINDINGS: The concept of 'epileptic encephalopathy' has progressively been elaborated by the International League Against Epilepsy according to growing clinical and laboratory evidence. It defines a process of neurological impairment caused by the epileptic activity itself and, therefore, potentially reversible with successful treatment, although to a variable extent. Epileptic activity interfering with neurogenesis, synaptogenesis, and normal network organization as well as triggering neuroinflammation are among the possible pathophysiological mechanisms leading to the neurological compromise. This differs from the newly introduced concept of 'developmental encephalopathy' which applies to where the epilepsy and developmental delay are both because of the underlying aetiology and aggressive antiepileptic treatment may not be helpful. SUMMARY: The understanding and use of correct terminology is crucial in clinical practice enabling appropriate expectations of antiepileptic treatment. Further research is needed to elucidate underlying pathophysiological mechanisms, define clear outcome predictors, and find new treatment targets.

Comparison of motor competence levels on two assessments across childhood.

This study compared performances and motor delay classifications for the Test of Gross Motor Development-2nd edition (TGMD-2) and the Körperkoordinationstest Für Kinder (KTK) in a sample of 424 healthy children (47% girls) between 5 and 10 years of age. Low-to-moderate correlations (r range = 0.34-0.52) were found between assessments across age. In general, both boys and girls demonstrated higher raw scores across age groups. However, percentile scores indicated younger children outperformed older children, denoting a normative percentile-based decrease in motor competence (MC) in the older age groups. In total, the TGMD-2 and KTK classified 39.4% and 18.4% children, respectively, as demonstrating very low MC (percentile ≤5). In conclusion, the TGMD-2 classified significantly more children with motor delays than the KTK and the differences between children's motor skill classification levels by these assessments became greater as the age groups increased. Therefore, the TGMD-2 may demonstrate more susceptibility to sociocultural influences and be more influenced by cumulative motor experiences throughout childhood. Low-to-moderate correlations between assessments also suggest the TGMD-2 and KTK may measure different aspects of MC. As such, it may be important to use multiple assessments to comprehensively assess motor competence.

Quantifying infant physical interactions using sensorized toys in a natural play environment.

Infants with developmental delays must be detected early in their development to minimize the progression of motor and neurological impairments. Our objective is to quantify how sensorized toys in a natural play environment can promote infant-toy physical interactions. We created a hanging elephant toy, equipped with an inertial measurement unit (IMU), a pressure transducer, and multiple feedback sensors, to be a hand-grasping toy. We used a 3 DoF robotic model with inputs from the IMU to calculate multiple kinematic metrics and an equation to calculate haptic metrics from the pressure transducer. Six typical infants were tested in the gym set-up. Three infants interacted with the toy for more than half the trial time. The youngest infant exhibited the largest toy displacement with ΔD = 27.6 cm, while the oldest infant squeezed the toy with the largest mean pressure of 4.5 kPa. More data on on both typical and atypical infants needs to be collected. After testing atypical infants in the SmarToyGym set-up, we will be able to identify interaction metrics that differentiate atypical and typical infants.

Empirically Identified Subgroups of Children Served in Part C Early Intervention Programs.

OBJECTIVE: Early intervention (EI) programs under Part C of the Individuals with Disabilities Education Act serve a developmentally heterogeneous population of infants and toddlers with or at risk of developmental delays or disabilities. The aim of this study was to identify empirically distinct subgroups of children in EI so as to inform early prognosis and service planning. METHODS: We applied mixture modeling to developmental assessment data from 1513 children who enrolled in a large, urban EI program between 2009 and 2013. The observed variables were children's EI-entry developmental quotients (DQs) in 5 domains (communication, cognitive, motor, adaptive, and personal-social) as assessed by the Battelle Developmental Inventory, Second Edition. RESULTS: A 4-class model showed the best fit to the data, revealing subgroups with distinct developmental profiles. Children in the first subgroup showed a severe delay in communication with less severe delays in the other domains. Children in the second subgroup likewise showed a severe delay in communication, but with comparably severe delays in the cognitive and motor domains. Profiles for the third and fourth subgroups showed the same overall patterns as those for the first and second subgroups, respectively, but to a less severe degree. Developmental trajectories differed by subgroup. CONCLUSION: Consideration of subgroups based on children's developmental assessment scores provides insight into underlying commonalities among children with different presenting diagnoses on entry into EI. The subgroups also have clinical relevance in terms of both practitioners' and parents' understanding of children's likely service needs and developmental trajectories.

Current knowledge of environmental exposure in children during the sensitive developmental periods / O estado atual do conhecimento sobre a exposição ambiental no organismo infantil durante os períodos sensíveis de desenvolvimento

Abstract: Objective: This study aims to identify the scientific evidence on the risks and effects of exposure to environmental contaminants in children during sensitive developmental periods. Data source: The search was performed in the Bireme database, using the terms: children's health, environmental exposure, health vulnerability, toxicity pathways and developmental disabilities in the LILACS, MEDLINE and SciELO systems. Data synthesis: Children differ from adults in their unique physiological and behavioral characteristics and the potential exposure to risks caused by several threats in the environment. Exposure to toxic agents is analyzed through toxicokinetic processes in the several systems and organs during the sensitive phases of child development. The caused effects are reflected in the increased prevalence of congenital malformations, diarrhea, asthma, cancer, endocrine and neurological disorders, among others, with negative impacts throughout adult life. Conclusion: To identify the causes and understand the mechanisms involved in the genesis of these diseases is a challenge for science, as there is still a lack of knowledge on children's susceptibility to many environmental contaminants. Prevention policies and more research on child environmental health, improving the recording and surveillance of environmental risks to children's health, should be an ongoing priority in the public health field.

Resumo: Objetivo: O presente estudo busca identificar as evidências científicas sobre os riscos e efeitos da exposição de contaminantes ambientais no organismo infantil durante os períodos sensíveis de seu desenvolvimento. Fonte de dados: As pesquisas foram feitas pelo banco de dados da Bireme, com os termos children's health, environmental exposure, health vulnerability, toxicity pathways e developmental disabilities nos sistemas Lilacs, Medline e SciELO. Síntese de dados: A criança difere do adulto por suas características singulares de ordem fisiológica, comportamental e do potencial de exposição a riscos frente às ameaças do ambiente. A exposição a agentes tóxicos é analisada por meio dos processos toxicocinéticos nos sistemas e órgãos durante as janelas sensíveis do desenvolvimento infantil. Os efeitos causados transparecem no aumento da prevalência de malformações congênitas, diarreia, asma, cânceres, distúrbios endócrinos e neurológicos, entre outros, com impactos negativos ao longo da vida adulta. Conclusão: Identificar as causas e compreender os mecanismos envolvidos na gênese desses agravos é um desafio que se impõe à ciência, visto que ainda há uma lacuna de conhecimento sobre a suscetibilidade infantil para muitos contaminantes ambientais. Políticas de prevenção e mais pesquisas em saúde ambiental infantil, que impulsionem o registro e a vigilância epidemiológica dos riscos ambientais à saúde da criança, devem ser uma prioridade contínua no campo da saúde pública.

Current knowledge of environmental exposure in children during the sensitive developmental periods.

OBJECTIVE: This study aims to identify the scientific evidence on the risks and effects of exposure to environmental contaminants in children during sensitive developmental periods. DATA SOURCE: The search was performed in the Bireme database, using the terms: children's health, environmental exposure, health vulnerability, toxicity pathways and developmental disabilities in the LILACS, MEDLINE and SciELO systems. DATA SYNTHESIS: Children differ from adults in their unique physiological and behavioral characteristics and the potential exposure to risks caused by several threats in the environment. Exposure to toxic agents is analyzed through toxicokinetic processes in the several systems and organs during the sensitive phases of child development. The caused effects are reflected in the increased prevalence of congenital malformations, diarrhea, asthma, cancer, endocrine and neurological disorders, among others, with negative impacts throughout adult life. CONCLUSION: To identify the causes and understand the mechanisms involved in the genesis of these diseases is a challenge for science, as there is still a lack of knowledge on children's susceptibility to many environmental contaminants. Prevention policies and more research on child environmental health, improving the recording and surveillance of environmental risks to children's health, should be an ongoing priority in the public health field.

DIAGNOSTIC CLASSIFICATION OF MENTAL HEALTH AND DEVELOPMENTAL DISORDERS OF INFANCY AND EARLY CHILDHOOD DC:0-5: SELECTIVE REVIEWS FROM A NEW NOSOLOGY FOR EARLY CHILDHOOD PSYCHOPATHOLOGY.

The Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood: Revised Edition (DC:0-5; ZERO TO THREE) is scheduled to be published in 2016. The articles in this section are selective reviews that have been undertaken as part of the process of refining and updating the nosology. They provide the rationales for new disorders, for disorders that had not been included previously in the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood: Revised Edition (DC:0-3R; ZERO TO THREE, 2005), and for changes in how certain types of disorders are conceptualized.