Understanding Behavior in Phelan-McDermid Syndrome

BackgroundPhelan-McDermid syndrome (PMS) or 22q13.3 deletion syndrome is a rare genetic disorder characterized by developmental delay, hypotonia and severely delayed speech. Behavioral difficulties are often reported in PMS, although knowledge of behavioral profiles and the interpretation of reported behavior remains limited. Understanding the meaning of behavior requires considering the context as well as other domains of functioning, for example the individual's level of cognitive, social and emotional development. Combining structured direct in-person neurodevelopmental assessments with contextual assessments to enable meaningful interpretations of reported behavior on functional dimensions across multiple units of analysis, as proposed by the RDoc framework, is essential. MethodsIn this article we present a structured multidisciplinary method of assessment through direct in-person neurodevelopmental assessments and assessment of contextual factors. Our study sample includes data of 33 children with an average age of 6.2 years (range 1.1 to 15.7) with PMS, obtained through individual in-person assessments in combination with parent informed questionnaires. We assessed developmental age using the Bayley-III, adaptive behavior was assessed with the Vineland screener, social-emotional development with the ESSEON-R and behavior by using the CBCL. ResultsOur results show a great deal of variability in phenotypic presentation with regard to behavior, symptom expression and symptom severity in individuals with PMS. The data on behavior is interpreted in the context of the individual's level of cognitive, adaptive development and the (genetic) context. Behavioral data showed high levels of withdrawn behavior and attention problems. More than half of the children showed borderline or clinical symptoms related to Autism Spectrum Disorder (ASD). ConclusionsThe interpretation of the meaning of certain behavior in PMS is often based on questionnaires and descriptions without taking the specific context of development into account. Combining questionnaires with direct in-person assessments measuring different domains of functioning should be considered a more accurate method to interpret the meaning of findings in order to understand behavior in rare genetic disorders associated with developmental delay such as PMS. Direct in-person assessment provides valuable and specific information relevant to understanding individual behavior and inform treatment as well as increase knowledge of the neurodevelopmental phenotype in individuals with PMS. More specific application of the proposed frameworks on behavior in PMS is desirable in making useful interpretations

How reliable and valid is the teacher version of the Strengths and Difficulties Questionnaire in primary school children?

Introduction The Strengths and Difficulties Questionnaire (SDQ) is validated for parents, but not yet for teachers in a broad age range of children. We conducted a cross-sectional study with 4-10 years old school children to investigate if the SDQ-T can be used instead of the validated but lengthy Teacher's Report Form (TRF) to acquire information about emotional and behavioral problems in the school community. Methods Teachers of 453 children from primary schools were approached. Teachers of 394 children (response rate 86.9%) with a mean age of 7.1 years filled in the SDQ-T (n = 387), the TRF (n = 349) or both (n = 342). We assessed reliability by calculating internal consistency and concurrent validity (using correlation coefficients, sensitivity, specificity) of the SDQ-T compared with the TRF. Results Internal consistency of the SDQ-T Total Difficulties Score (SDQ-T TDS; Cronbach alpha = 0.80), hyperactivity/inattention-(alpha = 0.86) and prosocial behavior (alpha = 0.81) was very good. Concurrent validity demonstrated a strong correlation of all subscales of the SDQ-T with the corresponding scale on the TRF (range 0.54-0.73), except for peer problems (0.46). Using a SDQ-T TDS cut-off score > 14, the SDQ-T had a good sensitivity (90%) and specificity (94%). Discussion The good reliability, validity and brevity of the SDQ-T make it an easily applicable questionnaire for obtaining information about emotional and behavioral problems from teachers in primary school children

Preface

AimThis was a one-year follow-up of families referred to support services after the parents visited the emergency department due to intimate partner violence, substance abuse or a suicide attempt. Its aim was to evaluate the well-being of any children. MethodsData on families identified a year earlier by the Amsterdam protocol were gathered from child protective services and parent and child self-reports in two Dutch regions from 2012-2015. ResultsWe included 399 children (52%) boys with a median age of eight years (range 1-18) in the study using child protective services data. Of the 101 families who participated in the first measurement, 67 responded one year after the parent's emergency department visit. The results showed that 20% of the children had no or minor problems, voluntary support services were involved in 60% of cases and child protective services were involved in 20%. Compared to their first assessment a year earlier, the children's psychosocial problems had not increased, but this could have been an underestimation due to selective responses. ConclusionThe Amsterdam protocol was valuable in referring families to voluntary support services, but given the ongoing problems in some families, professionals need to carefully monitor whether support services are sufficiently effectiv

The phenotypic spectrum of proximal 6q deletions based on a large cohort derived from social media and literature reports

Proximal 6q (6q11-q15) deletions are extremely rare and little is known about their phenotypic consequences. Since parents and caregivers now use social media to seek information on rare disorders, the Chromosome 6 Project has successfully collaborated with a Facebook group to collect data on individuals worldwide. Here we describe a cohort of 20 newly identified individuals and 25 literature cases with a proximal 6q deletion. Microarray results and phenotype data were reported directly by parents via a multilingual online questionnaire. This led to phenotype descriptions for five subregions of proximal 6q deletions; comparing the subgroups revealed that 6q11q14.1 deletions presented less severe clinical characteristics than 6q14.2q15 deletions. Gastroesophageal reflux, tracheo/laryngo/bronchomalacia, congenital heart defects, cerebral defects, seizures, and vision and respiratory problems were predominant in those with 6q14.2q15 deletions. Problems related to connective tissue (hypermobility, hernias and foot deformities) were predominantly seen in deletions including the COL12A1 gene (6q13). Congenital heart defects could be linked to deletions of MAP3K7 (6q15) or TBX18 (6q14.3). We further discuss the role of ten genes known or assumed to be related to developmental delay and/or autism (BAI3, RIMS1, KCNQ5, HTR1B, PHIP, SYNCRIP, HTR1E, ZNF292, AKIRIN2 and EPHA7). The most influential gene on the neurodevelopmental phenotype seems to be SYNCRIP (6q14.3), while deletions that include more than two of these genes led to more severe developmental delay. We demonstrate that approaching individuals via social media and collecting data directly from parents is a successful strategy, resulting in better information to counsel families

Developmental Coordination Disorder in children with specific language impairment:Co-morbidity and impact on quality of life

<p>Co-morbidity of Developmental Coordination Disorder (DCD) in children with specific language impairment (SLI) and the impact of DCD on quality-of-life (QOL) was investigated in 65 5-8 year old children with SLI (43 boys, age 6.8 +/- 0.8; 22 girls, age 6.6 +/- 0.8). The prevalence of DCD was assessed using DSM-IV-TR criteria (American Psychiatric Association (APA), 2000) operationally defined in the clinical practice guideline (CPG): movement ABC scores below 15th percentile, scores on DCDQ and/or MOQ-T below 15th percentile, absence of medical condition according to paediatric-neurological exam. Quality of life (QOL) was measured with the TNO-AZL-Child-Quality-Of-Life (TACQOL) Questionnaire filled out by parents for the SLI group with and without DCD, and compared to a reference group (N=572; age 6.9 +/- 0.9). The TACQOL covers 7 QOL domains: physical, motor, cognitive and social functioning, autonomy, positive and negative moods. Prevalence of DCD in children with SLI was 323%. In children with SLI, mean QOL scores were significantly lower in the autonomy, cognitive, social and positive moods domains compared to the reference group. Children with SLI and DCD differed from children with SLI without DCD by significantly lower mean overall-, motor-, autonomy-, and cognitive domain-QOL scores. Clinicians should be aware that about one third of children with SLI can also be diagnosed with DCD. Assessment of QOL is warranted in order to assess which domains are affected in children with SLI with or without DCD. (C) 2012 Elsevier Ltd. All rights reserved.</p>

Psychometric properties of the TACQOL-asthma, a disease-specific measure of health related quality-of-life for children with asthma and their parents

The disease-specific-TACQOL-asthma questionnaire measures health-status and appraisal of health-status. The TACQOL-asthma evaluates the personal feelings about problems in the domains, 'complaints, situations, emotions, treatment and medication'. The TACQOL-asthma can be used alone or in combination with the generic TACQOL. Our objective was to study the psychometric properties of the TACQOL-asthma-questionnaire. Responses of 298 parents and children with asthma (age eight to 16 years) in four paediatric practices in the northern part of the Netherlands were studied. The factor-analysis and item-domain correlation analysis show a moderate to strong correlation between the different items and their hypothesised domains. For all items, the correlation of the separate item with the hypothesized domain is stronger than with any other domain. The internal consistency (Cronbach's alpha) of the domains is moderate to good. Concurrent correlation with the Paediatric-Asthma-Quality-of-Life-Questionnaire- (PAQLQ) was significant. Effect sizes of differences between asthma-severity classes in TACQOL-asthma and PAQLQ-scores were similar and of clinical importance. This study validates the TACQOL-asthma as a new disease-specific questionnaire. The TACQOL-asthma ensures a measurement of health status as well as appraisal of health problems. The TACQOL-asthma has good reliability and validity properties to serve as an evaluative and discriminate disease-specific health-related-quality-of-life questionnaire. © 2006 Edward Arnold (Publishers) Ltd

Validity and reliability of the Movement Assessment Battery for Children-2 Checklist for children with and without motor impairments

Aim The aim of this study was to investigate the validity and reliability of the Movement Assessment Battery for Children-2 Checklist (MABC-2). METHOD Teachers completed the Checklist for 383 children (age range 5-8y; mean age 6y 9mo; 190 males; 193 females) and the parents of 130 of these children completed the Developmental Disorder Coordination Questionnaire 2007 (DCDQ'07). All children were assessed with the MABC2 Test. The internal consistency of the 30 items of the Checklist was determined to measure reliability. Construct validity was investigated using factor analysis and discriminative validity was assessed by comparing the scores of children with and without movement difficulties. Concurrent validity was measured by calculating correlations between the Checklist, Test, and the DCDQ'07. Incremental validity was assessed to determine whether the Checklist was a better predictor of motor impairment than the DCDQ'07. Sensitivity and specificity were investigated using the MABC-2 Test as reference standard (cut-off 15th centile). RESULTS The Checklist items measure the same construct. Six factors were obtained after factor analysis. This implies that a broad range of functional activities can be assessed with the Checklist, which renders the Checklist useful for assessing criterion B of the diagnostic criteria for DCD. The mean Checklist scores for children with and without motor impairments significantly differed (p <0.001). The scores for the Checklist/Test and DCDQ' 07 were significantly correlated (r(S) = -0.38 and p <0.001, and r(S) = -0.36 and p <0.001, respectively). The Checklist better predicted motor impairment than the DCDQ'07. Overall, the sensitivity was low (41%) and the specificity was acceptable (88%). INTERPRETATION The Checklist meets standards for validity and reliability

Mean scores, standard deviations (SD) and clinical cut-off scores (p90^* & p80) for the teacher SDQ.

<p>Mean scores, standard deviations (SD) and clinical cut-off scores (p90^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0176605#t002fn001" target="_blank">*</a>} & p80) for the teacher SDQ.</p

Is there an effect of intranasal insulin on development and behaviour in Phelan-McDermid syndrome?: A randomized, double-blind, placebo-controlled trial

Phelan-McDermid syndrome (PMS) or 22q13.3 deletion syndrome is a rare neurodevelopmental disorder with at least 60 children and 35 adults diagnosed in the Netherlands. Clinical features are moderate to severe intellectual disability and behavioural problems in the autism spectrum. Other researchers had observed a beneficial effect of intranasal insulin on development and behaviour in a pilot study in six children with PMS. To validate this effect, we conducted a randomized, double-blind, placebo-controlled clinical trial using a stepped-wedge design. From March 2013 to June 2015, 25 children aged 1-16 years with a molecularly confirmed 22q13.3 deletion including the SHANK3 gene participated in the clinical trial for a period of 18 months. Starting 6 months before the trial, children were systematically assessed for cognitive, language and motor development and for adaptive, social and emotional behaviour every 6 months. The second, third and fourth assessments were followed by daily nose sprays containing either intranasal insulin or intranasal placebo for a 6-month period. A fifth assessment was done directly after the end of the trial. Intranasal insulin did not cause serious adverse events. It increased the level of developmental functioning by 0.4-1.4 months per 6-month period, but the effect was not statistically significant in this small group. We found a stronger effect of intranasal insulin, being significant for cognition and social skills, for children older than 3 years, who usually show a decrease of developmental growth. However, clinical trials in larger study populations are required to prove the therapeutic effect of intranasal insulin in PMS