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Aim The Rett Syndrome Gross Motor Scale (RSGMS) is an observational measurement, assessing gross motor skills in individuals with Rett syndrome. A Dutch version is lacking. The current study aims to translate and cross-culturally adapt the original RSMGS to Dutch and assess its inter-rater and intra-rater reliability. Design Translation and cross-cultural adaptation were performed in concordance with internationally accepted guidelines. A pretest was performed, and expert validation was assured. Video data of three girls with Rett syndrome was independently assessed by 27 physiotherapists via an online webinar to measure inter-rater reliability. Additionally, videos of 17 individuals with Rett syndrome were scored twice by two raters to assess intra-rater reliability. The reliability of the total score, the three subscale scores and the new items were analyzed using Intraclass Correlation Coefficients (ICC). Results Good comprehensibility and expert validation of the RSMGS-NL was achieved, and four items were added to the original scale. Inter-rater reliability for the total score was excellent (ICC 0.97, 95% CI 0.89-0.99), and good to perfect inter-rater reliability for the three subscales; Sitting, Standing & walking and Challenge was found (ICC values 1.0 (95% CI 0), 0.98 (95% CI 0.91-0.99) and 0.82 (95% CI 0.93-0.99) respectively). The intra-rater reliability was excellent for the total test score (ICC 0.98, 95% CI 0.97-0.99) and good to excellent for the subscale scores (ICC values 0.87 (95% CI 0.75-0.94), 0.99 (95% CI 0.98-1.0) and 0.97 (95% CI 0.95-0.99) respectively). The four new items (Standing to sitting, walking down a slope, ascending the stairs, descending the stairs) showed good to excellent intra-rater reliability. Conclusion The RSGMS-NL is a reliable measure of gross motor skills in Dutch individuals with Rett syndrome.

Alcohol consumption during pregnancy can lead to fetal alcohol spectrum disorders (FASD). FASD is a spectrum of structural, functional, and neurodevelopmental problems with often lifelong implications, affecting communities worldwide. It is a leading preventable form of intellectual disabilities and therefore warrants effective prevention approaches. However, well-intended FASD prevention can increase stigmatization of individuals with FASD, women who consume or have consumed alcohol during pregnancy, and non-biological parents and guardians of individuals with FASD. This narrative review surveyed the literature on stigmatization related to FASD. Public stigma appears to be the most common form of stigma studied. Less is known about FASD-related self-stigma, stigma by association, and structural stigma. Accordingly, the current literature on FASD-related stigma does not appear to provide sufficient guidance for effectively reducing FASD-related stigma. However, lessons can be learned from other related health topics and the use of a systematic approach for the development of health promotion programs, namely Intervention Mapping.

Difficulties with communication have a profound impact on the lives of individuals with Rett syndrome and their caregivers. Globally, many families report difficulty accessing appropriate and timely information and services from professionals with expertise in augmentative and alternative communication (AAC) as it pertains to Rett syndrome. To address this need, international consensus-based guidelines for managing the communication of individuals with Rett syndrome were developed by combining available evidence and lived experience with expert opinion. A two-phase Delphi survey was built on statements and recommendations extracted from a review of over 300 pieces of literature combined with survey responses from communication professionals and caregivers. All statements that reached a pre-determined threshold of ≥70% agreement were incorporated into guidelines that consist of 268 statements and recommendations relating to (a) rights of the individual; (b) beliefs and attitudes of communication partners; (c) professional knowledge and team work; (d) strategies to optimize engagement; (e) assessment; and (f) intervention (targets and goals, techniques), including the use of AAC. To date, this project is the largest of its kind, with 650 participants from 43 countries contributing to development of consensus-based guidelines for Rett syndrome.

Background: Unhealthy alcohol use is a public health issue, prioritized by the World Health Organization (WHO) for prevention and reduction. Ukraine falls in the highest WHO category of "years of life lost" due to alcohol use. Objective: To investigate perceptions of alcohol consumption in a sample of youth and adults in western Ukraine. Methods: In-depth semi-structured interviews were conducted with 38 adult stakeholders (aged 21-63 years), and 81 adolescents and young adults (aged 12-21 years) completed paper-and-pencil open-ended questions. A combined deductive-inductive thematic analysis of these qualitative data resulted in an initial coding scheme for both parts of the data. These initial codes were organized into patterns, which were further condensed to four themes. Results: The four themes that were developed are: (1) The general historical, socio-economic-political situation and its relation to alcohol use, (2) Alcohol in the home and daily environment, (3) Alcohol use, related feelings, peers, family, and burden to health, and (4) Perceptions of the consequences of alcohol (mis)use. Conclusions: Respondents indicated awareness that daily consumption, also in youth, as well as binge drinking and childhood sipping constitute a risk to health. These risks were described in the context of easy availability, low pricing, and peer pressure. The respondents mentioned awareness that alcohol dependence (AD) of parents affected families with the risk of disadvantageous child development. Interventions may include targeting current norms, stigmatizing beliefs and supporting subjects in developing coping skills. 2020 The Author(s). Published with license by Taylor & Francis Group, LLC This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. Toornstra, A (reprint author), Maastricht Univ, Fac Psychol & Neurosci, Dept Neuropsychol & Neuropharmacol, NL-6200 MD Maastricht, Netherlands. annet.toornstra@maastrichtuniversity.nl

The study aims to establish demographically corrected, pediatric norms for the computerized Delayed Matching to Sample (DMS) test, a measure of "visual matching ability and short-term visual recognition memory, for non-verbalisable problems". The DMS was administered to n = 184 children aged 5.10 to 14.5 years old. The DMS is a 4-choice recognition task of non-verbal, abstract patterns. The child has "to select, among four different choice patterns, the one that matches a complex visual pattern presented," i.e., (the target stimulus). The DMS consists of two conditions: a) the overt condition in which the target stimulus and four choice patterns are shown simultaneously and b) the covert condition, in which the choice patterns are shown after the target pattern is covered. The DMS test provides three outcome measures: the accuracy score (i.e., the number of correct patterns selected), latency (i.e., the response speed) and the probability of making an error after an incorrect response. These outcome measures were calculated for both conditions and for both conditions combined. Results showed that demographic variables, such as age, sex, and/or level of parental education (LPE) affected scores on these outcome measures. Based on these data, demographically corrected norms were established for all outcome measures, per condition and for both conditions combined.

(1) Background: Prader–Willi syndrome (PWS) is characterized by hyperphagia, resulting in morbid obesity if not controlled. The primary aim of this study was to investigate whether PWS patients show altered activation of brain areas involved in hunger. As a secondary objective, we assessed whether there is an association between these brain areas and several endocrine and metabolic factors in the fasting state. (2) Methods: 12 PWS adults and 14 healthy controls (siblings) performed a food-related experimental task after an overnight fast while brain activation in regions of interest was measured by functional MRI. (3) Results: In controls, significantly more activation was found in the left insula (p = 0.004) and the bilateral fusiform gyrus (p = 0.003 and 0.013) when the individuals were watching food as compared to non-food pictures, which was absent in PWS patients. Moreover, in PWS adults watching food versus non-food pictures a significant negative correlation for glucose and right amygdala activation (p_fwe = 0.007) as well as a positive correlation for leptin and right anterior hippocampus/amygdala activation (p_fwe = 0.028) was demonstrated. No significant associations for the other hormonal and metabolic factors were found. (4) Conclusions: PWS individuals show aberrant food-related brain activation in the fasting state. Leptin is associated with activation within the neural motivation/reward circuitry, while the opposite is true for glucose.

Here, we describe a dataset with information about monogenic, rare diseases with a known genetic background, supplemented with manually extracted provenance for the disease itself and the discovery of the underlying genetic cause. We assembled a collection of 4166 rare monogenic diseases and linked them to 3163 causative genes, annotated with OMIM and Ensembl identifiers and HGNC symbols. The PubMed identifiers of the scientific publications, which for the first time described the rare diseases, and the publications, which found the genes causing the diseases were added using information from OMIM, PubMed, Wikipedia, whonamedit.com, and Google Scholar. The data are available under CC0 license as spreadsheet and as RDF in a semantic model modified from DisGeNET, and was added to Wikidata. This dataset relies on publicly available data and publications with a PubMed identifier, but by our effort to make the data interoperable and linked, we can now analyse this data. Our analysis revealed the timeline of rare disease and causative gene discovery and links them to developments in methods., Measurement(s) Gene_Associated_With_Disease • genetic disorder Technology Type(s) digital curation Factor Type(s) disease Sample Characteristic - Organism Homo sapiens Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.14140661

The study aims to establish demographically corrected norms for three computerized tasks measuring different aspects of visual short-term memory (VSTM) in Ukrainian schoolchildren. These tasks measure respectively visual STM (the Pattern Recognition Memory (PRM) test), spatial STM (the Spatial Span (SSP) task), and visual spatial STM (the Paired Associates Learning (PAL) task). All tasks were administered to n = 186 children aged 5.10 years to 14.5 years old to evaluate the influence of demographic variables. Relevant demographic factors that influence task scores (VSTM), i.e., age and level of parental education, are identified and in keeping with the current literature. No sex differences were found. Based on these data, regression-based, demographically corrected norms were established per task. This approach to constructing norms differs from how (worldwide) PRM, SSP, and/or PAL norms have been constructed traditionally. In the latter approach, norms are calculated for each age group separately and without correcting for level of parental education, whereas in the regression-based normative method, multiple regression models are used to compute the expected test scores of an individual (rather than the subgroup means that are used in the traditional approach). Consequently, the regression-based norms for the PRM, SSP, and PAL presented in this paper are individualized, taking into account the unique characteristics of the individual that is tested on these tasks. Last, the confidence intervals of the PRM scores of the Ukrainian schoolchildren and the western norm group largely overlapped, except for the youngest age group, which adds to the literature about cultural effects on cognition.

In 2018, the authors published their analysis of nine online case reports by the Euthanasia Review Committee in the Netherlands, involving people with intellectual disability and/or autism spectrum disorder who were given euthanasia. In this commentary, they reflect further on the challenges of assessing "unbearable suffering without prospect of improvement," which is one of the Dutch legal due care criteria. Two more recent case reports are presented in detail, where doctors struggled to assess and sometimes came to divergent conclusions. In both cases, limitations resulting from the intellectual disability and autism spectrum disorder were seen by physicians as causes of unbearable suffering, leading them to agreeing to the patient's euthanasia request. The authors discuss their concern about the implications of accepting the effects of lifelong disability as reasons for euthanasia, not only for individuals but for society as a whole.

Background: Rett syndrome (RTT) is a neurological disorder characterized by a broad spectrum of symptoms. Communication is a major area of difficulty. Use of eye tracking technology offers a potentially effective method of communication when underpinned by intact oculomotor function. In this study, oculomotor function was assessed using electronystagmography (ENG). However, challenges were encountered when examining individuals with RTT.Purpose: To improve oculomotor examination in individuals with RTT by evaluating the challenges encountered during ENG examination.Material and methods: Oculomotor function was examined in 17 girls and young women with RTT and 16 typically developing (TD) individuals using ENG. Observational analysis of both performance and results indicated that challenges in examination were mainly related to quality of attention and quality of signals. Subsequently these outcome values were explored quantitatively according to percentage looking time for attention and drift for signal quality.Results: A significantly reduced level of attention and suboptimal electrode signals were evident in the RTT group when compared with the TD group for all tests except torsion swing.Conclusion: The challenges in testing confirm that regular oculomotor examination should be adjusted to meet the needs of individuals with RTT. It is hypothesized that the RTT group's higher quality of attention on the torsion swing can be explained by the more forceful vestibular rather than visual-ocular stimulus operating in this test. Suggested adaptations include reducing the number of electrodes, changing the picture stimuli and bringing them closer, performing observational assessments rather than ENG, and using virtual reality goggles. (C) 2018 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Individuals with an intellectual disability (ID) have sexual feelings, are sexually active and have ideas about sexuality. There is limited information available about the ideas and experiences regarding sexual expression, interests and knowledge of sexual rights in this population. This study aims to identify the ideas, expressions, barriers to sexuality, experienced by people with IDs, using the Nominal Group Technique (NGT). The NGT was used to explore the views of people with mild ID on sexual needs and issues. NGT is a structured and specific form of focus group research. It is a single-question' technique that combines quantitative and qualitative methods of data collection for relatively small groups. NGT involves four steps: silent generation of ideas, round robin recording of ideas, clarification of ideas, and ranking of ideas. It was an inclusive research project: people with an ID were involved in the design, planning, performance, and analysis of the study. In total 39 people with mild IDs were able to explore their experiences and ideas on sexuality. They were able to answer questions like: What are their needs? What are their problems? They were capable of expressing their views, needs and barriers on sexuality and sexual rights. The most important items were the relationship between two people (47%), sex and sex related subjects as sex education (23%), and feeling safe and comfortable (10%). People with mild IDs are capable of expressing their views on sexuality and sexual rights. The participants stated that they need support in achieving these rights. The nominal group technique appears to be an appropriate methodology on sensitive issues as sexuality and sexual rights.

Background Fetal alcohol spectrum disorders (FASD) is a group of conditions resulting from prenatal alcohol exposure (PAE). Patients with FASD experience a variety of neuropsychological symptoms resulting from central nervous system impairment. Little is known about sleep disorders associated with PAE. The objective of this study was to investigate sleep problems related to FASD. Methods Forty patients (median age 8 years (6; 11)) diagnosed with FASD and forty typically developing children (median age 10 years (8; 13)) were recruited for the 1st phase of the study. In the 1st phase, the screening of sleep problems was performed with Child Sleep Habit Questionnaire (CSHQ) filled in by a caregiver. Those of the FASD group who scored above 41 points were qualified to the 2nd phase of the study and had an in-lab attended polysomnography (PSG) performed. The measurements consisted of electroencephalogram, electrooculograms, chin and tibial electromyogram, electrocardiogram, ventilatory monitoring, breathing effort, pulse oximetry, snoring and body position. Their results were compared to PSG laboratory reference data. Results The number of participants with sleep disturbances was markedly higher in the FASD group as compared to typically developing children (55% vs. 20%). The age-adjusted odds ratio for a positive result in CSHQ was 4.31 (95% CI: 1.54–12.11; p = 0.005) for FASD patients as compared to the control group. Significant differences between the FASD as compared to the typically developing children were observed in the following subscales: sleep onset delay, night wakings, parasomnias, sleep disordered breathing, and daytime sleepiness. Children from the FASD group who underwent PSG experienced more arousals during the sleep as compared with the PSG laboratory reference data. The respiratory indices in FASD group appear higher than previously published data from typically developing children. Conclusion The results support the clinical observation that sleep disorders appear to be an important health problem in individuals with FASD. In particular distorted sleep architecture and apneic/hypopneic events need further attention.

© 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), With a diverse set of neuronal and glial cell populations, Central Nervous System (CNS) has one of the most complex structures in the body. Intercellular communication is therefore highly important to coordinate cell-to-cell interactions. Besides electrical and chemical messengers, CNS cells also benefit from another communication route, what is known as extracellular vesicles, to harmonize their interactions. Extracellular Vesicles (EVs) and their subtype exosomes are membranous particles secreted by cells and contain information packaged in the form of biomolecules such as small fragments of DNA, lipids, miRNAs, mRNAs, and proteins. They are able to efficiently drive changes upon their arrival to recipient cells. EVs actively participate in all stages of CNS development by stimulating neural cell proliferation, differentiation, synaptic formation, and mediating reciprocal interactions between neurons and oligodendrocyte for myelination process. The aim of the present review is to enlighten the presence and contribution of EVs at each CNS developmental milestone.

BackgroundFetal alcohol spectrum disorders (FASD) is a group of conditions resulting from prenatal alcohol exposure (PAE). Patients with FASD experience a variety of neuropsychological symptoms resulting from central nervous system impairment. Little is known about sleep disorders associated with PAE. The objective of this study was to investigate the prevalence and characterize sleep problems among individuals with FASD.Methods40 patients from FASD diagnostic center (median age 8 years (6; 11)) diagnosed with one of the FASD diagnosis and 40 patients from the control group (median age 10 years (8; 13)) participated in the study. In the 1st phase, the screening of sleep problems was performed with Child Sleep Habit Questionnaire (CSHQ) filled in by a caregiver. Those who scored above 41 points were qualified to the 2nd phase of the study in which in-lab attended polysomnography (PSG) was performed. The measurements consisted of electroencephalographic channels, left and right electrooculograms, chin electromyogram, left and right tibialis electromyogram, electrocardiogram, ventilatory monitoring, breathing effort, pulse oximetry, snoring and body position.ResultsThe number of participants with sleep disturbances was markedly higher in the study group as compared to controls (55% vs. 20%). The age-adjusted odds ratio for a positive result in CSHQ was 4.31 (95% CI: 1.54-12.11; p=0.005) for FASD patients as compared to the control group. Significant differences between the study and control groups were observed in the following subscales: sleep onset delay, night wakings , parasomnias , sleep disordered breathing, and daytime sleepiness. In PSG children from the FASD group and children from the control group experienced more arousals during the sleep than the children from the laboratory control group. ). There were no significant differences in comparison of respiratory indexes between FASD and control groups although indices in both groups were higher than previously published data for a normal population.ConclusionSleep disorders are more common among individuals with FASD than among healthy children. As distorted sleep can affect daily performance and worsen neurodevelopmental issues, it is vital for the pediatricians and other FASD specialists to include the question about sleep in the anamnesis.

The aim of the study was to establish demographically representative norms for tasks measuring goal setting, and more specifically planning and reasoning in children. Three tasks were administered to n = 195 Ukrainian children aged 5.10 to 14.5 years old: the Spatial Working Memory (SWM), the Stockings of Cambridge (SOC) test, and the Naglieri Nonverbal Ability Test (NNAT). Main outcome per test was accuracy: i.e., the total number correct for the SOC and NNAT, and the total amount of incorrect responses for the SWM. Correlations among accuracy measures varied from − 0.51 to 0.60, indicating these tasks measure related but at the same time unique constructs. Higher age was associated with more accurate test performances on all outcome measures. On the NNAT, we found a curvilinear association between age and accuracy, indicating that younger children’s NNAT accuracy scores increased more with age compared with older children. We found a cubic age effect on accuracy for the SWM and SOC: i.e., test scores were relatively stable at younger and older ages, with a curvilinear increase in test scores in the other age groups. Demographically corrected norms were calculated and presented per test. These indicated that sex was not associated with accuracy scores on any of the tests. Last, a higher level of parental education (LPE) was associated with higher accuracy scores, but only on the NNAT. We conclude that demographic variables in norm analyses enhance insight in the scores and allow for application in clinical settings and research.

Substance use disorders are serious behavioral health problems, and problematic substance use often leads to severe consequences for an individual’s own health and negatively impacts others’ lives. Preventing substance misuse and substance use disorders is imperative. The development of effective prevention intervention programs, including successful health promotion strategies, is complex mainly due to knowledge gaps and the presence of complicated contextual factors. If key interfering factors are overlooked, ineffective or counterproductive programs can, and do, result. For effective prevention of substance use disorders and their associated negative consequences, there is a need for planning systematic, theory-driven, and evidence-based health promotion programs. This chapter provides background information and a framework for the systematic development of health promotion programs for social workers and allied health professionals to apply in addressing substance misuse and related problems.

Author(s): Zhang, Dajie; Bedogni, Francesco; Boterberg, Sofie; Camfield, Carol; Camfield, Peter; Charman, Tony; Curfs, Leopold; Einspieler, Christa; Esposito, Gianluca; De Filippis, Bianca; Goin-Kochel, Robin P; Hoglinger, Gunter U; Holzinger, Daniel; Iosif, Ana-Maria; Lancioni, Giulio E; Landsberger, Nicoletta; Laviola, Giovanni; Marco, Eva M; Muller, Michael; Neul, Jeffrey L; Nielsen-Saines, Karin; Nordahl-Hansen, Anders; O'Reilly, Mark F; Ozonoff, Sally; Poustka, Luise; Roeyers, Herbert; Rankovic, Marija; Sigafoos, Jeff; Tammimies, Kristiina; Townend, Gillian S; Zwaigenbaum, Lonnie; Zweckstetter, Markus; Bolte, Sven; Marschik, Peter B

Rett syndrome (RTT) is a monogenic rare disorder that causes severe neurological problems. In most cases, it results from a loss‐of‐function mutation in the gene encoding methyl‐CPG‐binding protein 2 (MECP2). Currently, about 900 unique MECP2 variations (benign and pathogenic) have been identified and it is suspected that the different mutations contribute to different levels of disease severity. For researchers and clinicians, it is important that genotype–phenotype information is available to identify disease‐causing mutations for diagnosis, to aid in clinical management of the disorder, and to provide counseling for parents. In this study, 13 genotype–phenotype databases were surveyed for their general functionality and availability of RTT‐specific MECP2 variation data. For each database, we investigated findability and interoperability alongside practical user functionality, and type and amount of genetic and phenotype data. The main conclusions are that, as well as being challenging to find these databases and specific MECP2 variants held within, interoperability is as yet poorly developed and requires effort to search across databases. Nevertheless, we found several thousand online database entries for MECP2 variations and their associated phenotypes, diagnosis, or predicted variant effects, which is a good starting point for researchers and clinicians who want to provide, annotate, and use the data.

Alcohol exposure during pregnancy affects the development of the fetus in various ways and may lead to Fetal Alcohol Spectrum Disorders (FASD). FASD is one of the leading preventable forms of neurodevelopmental disorders. In the light of prevention and early intervention, knowledge on how ethanol exposure induces fetal damage is urgently needed. Besides direct ethanol and acetaldehyde toxicity, alcohol increases oxidative stress, and subsequent general effects (e.g., epigenetic imprinting, gene expression, and metabolite levels). The current review provides an overview of the existing knowledge about specific downstream pathways for FASD that affects e.g., the SHH pathway, cholesterol homeostasis, neurotransmitter signaling, and effects on the cytoskeleton. Available human data vary greatly, while animal studies with controlled ethanol exposition are only to a certain limit transferable to humans. The main deficits in knowledge about FASD are the lack of pathophysiological understanding and dose-response relationships, together with the lack of reliable biomarkers for either FASD detection or estimation of susceptibility. In addition to single outcome experiments, omics data should be generated to overcome this problem. Therefore, for future studies we recommend holistic data driven analysis, which allows integrative analyses over multiple levels of genetic variation, transcriptomics and metabolomics data to investigate the whole image of FASD development and to provide insight in potential drug targets for intervention. ispartof: MOLECULAR PSYCHIATRY vol:24 issue:1 pages:10-17 ispartof: location:England status: published

This study aimed to determine whether there is a relationship between abnormal foot position and standing and walking ability in individuals with Rett syndrome (RTT), a rare neurological condition primarily affecting females, often accompanied by impaired gross motor function and musculoskeletal deformities. Through means of an online survey, physiotherapists were asked to share information about their work and experience with individuals with RTT. They were asked about their clients' scores on the Rett Syndrome Gross Motor Scale and measures of their foot deformity, passive range of motion of dorsiflexion of the foot, use of supportive footwear, pressure load on the foot, and symmetry in weight bearing. 45 physiotherapists gave answers relating to 67 individuals with RTT who ranged in age from 2 to over 50 years. Almost 80% had an abnormal foot position which required support of special shoes or orthoses. Approximately 55% experienced abnormal pressure load on the foot and 65% demonstrated asymmetrical weight-bearing; 22% could sit independently and 17% were able to stand and walk independently. Of all the variables investigated, only abnormal distribution of pressure on the foot and asymmetry in weight bearing through the legs were found to be (negatively) correlated with standing and walking ability. Physiotherapists can use this information to give advice on othopedic support for the feet of individuals with RTT.

Purpose of review This article reviews the current molecular genetic studies, which investigate the genetic causes of Rett syndrome or Rett-like phenotypes without a MECP2 mutation. Recent findings As next generation sequencing becomes broadly available, especially whole exome sequencing is used in clinical diagnosis of the genetic causes of a wide spectrum of intellectual disability, autism, and encephalopathies. Patients who were diagnosed with Rett syndrome or Rett-like syndrome because of their phenotype but were negative for mutations in the MECP2, CDKL5 or FOXG1 genes were subjected to whole exome sequencing and the results of the last few years revealed yet 69 different genes. Many of these genes are involved in epigenetic gene regulation, chromatin shaping, neurotransmitter action or RNA transcription/translation. Genetic data also allows to investigate the individual genetic background of an individual patient, which can modify the severity of a genetic disorder. Summary We conclude that the Rett syndrome phenotype has a much broader underlying genetic cause and the typical phenotype overlap with other genetic disorders. For proper genetic counselling, patient perspective and treatment it is important to include both phenotype and genetic information.

Objectives: Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are two syndromes that are caused by the same chromosomal deletion on 15q11.2-q13. Due to methylation patterns, different genes are responsible for the two distinct phenotypes resulting in the disorders. Patients of both disorders exhibit hypotonia in neonatal stage, delay in development and hypopigmentation. Typical features for PWS include hyperphagia, which leads to obesity, the major cause of mortality, and hypogonadism. In AS, patients suffer from a more severe developmental delay, they have a distinctive behaviour that is often described as unnaturally happy, and a tendency for epileptic seizures. For both syndromes, we identified and visualised molecular downstream pathways of the deleted genes that could give insight on the development of the clinical features. Methods: This was done by consulting literature, genome browsers and pathway databases to identify molecular interactions and to construct downstream pathways. Results: A pathway visualisation was created and uploaded to the open pathway database WikiPathways covering all molecular pathways that were found. Conclusions: The visualisation of the downstream pathways of PWS- and AS-deleted genes shows that some of the typical symptoms are caused by multiple genes and reveals critical gaps in the current knowledge.

Sleep problems are reported to be extremely prevalent in individuals with developmental disabilities. The consensus guidelines for Angelman syndrome (AS) consider abnormal sleep-wake cycles and diminished need for sleep as associated features. We report an integrative research review and a meta-analysis of studies with sleep as the primary aim of investigation in an AS sample. 14 studies met eligibility criteria with half of them being surveys. Thirteen of the 17 conceptually formed sleep disorder item-groups showed to be significant for individuals with AS. There is evidence that arousal during sleep, somnolence and possibly short sleep duration are the primary sleep problems in individuals with AS. According to the results of this review and meta-analyses, there is clear evidence for sleep problems in individuals with AS. Individual effect sizes remain overall small, but nevertheless findings suggest disorders of arousal and sleepiness to be distinctive. In light of these findings, other sleep complaints in individuals with AS should be carefully examined. Consistent standards for research on sleep in individuals with AS are critical for new lines of investigation. (C) 2017 Elsevier Ltd. All rights reserved.

Background Sexual rights and sexuality are important aspects of quality of life, also for people with intellectual disabilities (IDs). However, providing support in this area to people with ID poses some challenges. In this study, the content of individual support plan (ISP) documents was analysed to determine the extent to which sexuality and sexual rights are addressed in part of the ISP documents. Method Content analysis was carried out on a sample of 187 ISP documents from seven different service provider organisations in the Netherlands. First, we conducted a lexical search using terms related to sexuality and sexual health. The retrieved segments were then analysed. Results A total of 159 ISP documents (85%) of 60 men and 99 women contained some reference to aspects of sexuality. However, these references were mostly descriptive and offered little guidance in terms of providing support. Moreover, these notations mostly described negative or problematic aspects of sexuality. References to sexual education, treatment, intervention programs or support strategies were rarely found in the ISP documents. Conclusions Although sexuality is addressed in most ISP documents, there is little information available about the provision of professional support in this area that would give people the opportunity to exert sexual rights. As sexuality and exerting sexual rights are important for people with ID as well as for other people, it is recommended that issues surrounding proactive sex education, shared decision-making and the implementation of sexual healthcare plans are addressed in the ISP.

AimsTo assess the rates of incontinence and associated psychological problems in children, adolescents and adults with Down Syndrome, a genetic syndrome caused by partial or complete triplication (trisomy) of chromosome 21 and characterized by typical facial features, a physical growth delay and mild or moderate intellectual disability.MethodsThree hundred and seventeen persons with Down Syndrome (4-51 years) were recruited through a German parent support group (59.6% male, mean age 19.2 years). The Parental Questionnaire: Enuresis/Urinary Incontinence, the Incontinence Questionnaire-Pediatric Lower Urinary Tract Symptoms, as well as the Developmental Behavior Checklist (DBC) for parents or for adults were filled out by parents or care-givers.Results17.2% of the sample had nocturnal enuresis, 15.9% had daytime urinary incontinence, and 14.2% had fecal incontinence. Incontinence was present in 64.0% of young children (4-12 years), 10.3% of teens (13-17 years), 12.8% of young adults (18-30 years) and in 22.4% of older adults (>30 years). 13.6% of children and 8.4% of adults had a DBC score in the clinical range. 19.5% of children and 27.8% of adults with incontinence had behavioral problems. There was a significant association between nocturnal enuresis, daytime urinary incontinence and clinical DBC scores in adults.ConclusionsIncontinence in Down Syndrome is mainly present in young children and increases in older adults. Behavioral comorbidity is associated with incontinence only in adults with Down Syndrome. Screening and treatment of incontinence in individuals with Down Syndrome is recommended.

Existing sex education programmes have failed in involving people with intellectual disabilities in the development of these programmes. Not involving the target population decreases the likelihood that the sex education programme will be effective. This study was conducted to assess the perspectives of people with intellectual disabilities on several sexuality-related topics. Semi-structured interviews were held with 20 people with intellectual disabilities covering topics such as: sex education, relationships, sex, social media, parenthood and support. The reported frequency of sex education the participants receive is low. Their knowledge regarding sex education is mainly limited to topics such as safe sex, contraception and STI's and tends to be superficial. Additionally, knowledge on safe sex does not always translate to safe sex behaviour. Finally, relationships are important for most participants; mainly because they don't want to be alone. Findings from both this study and literature shows that there seems to be a need for high quality sex education. Topics to consider to include are: online relationships, social media and parenthood. It would also be beneficial to focus on sexuality-related skills. Finally, to increase the effectiveness of a sex education programme, it is advisable that a theory-and evidence-based framework, such as Intervention Mapping, is used for its development.

In circadian rhythm sleep–wake disorders precision medicine is less developed than in other medical disciplines mainly because homeostatic sleep and circadian timing have a very complex phenotype with multiple genetic regulation mechanisms. However, biomarkers, phenotyping and psychosocial characteristics are increasingly used. Devices for polysomnography, actigraphy and sleep-tracking applications in mobile phones and other consumer devices with eHealth technologies are increasingly used. Also sleep-related questionnaires and the assessment of co-morbidities influencing sleep in circadian rhythm sleep–wake disorders are major contributors to precision sleep medicine. To further strengthen the (pharmaco-)genetic and biomarker pillar, technology needs to be evolved further. Routinely measuring treatment results using patient-reported outcome measures and clinical neurophysiological instruments will boost precision sleep medicine.

Dim Light Melatonin Onset (DLMO) is a reliable marker of the endogenous circadian rhythm. To determine if sleep timing can predict DLMO, we investigated the relationship between sleep timing and DLMO in patients in various circadian sleep-wake rhythm disorders (CSWRDs), ages and genders. We found that correlations were only moderate between DLMO and sleep-onset in the complete data-set, but they increased in patients with delayed sleep-wake phase disorder (DSWPD), DSWPD patients with a regular sleep pattern and patients with advanced sleep-wake phase disorder (ASWPD); the levels of correlation were r = 0.542, 0.657, 0.728 and 0.814, respectively. In DSWPD patients with a regular sleep pattern, mid-sleep strongly correlated (r = 0.839) with DLMO. Correlation in other CSRWDs was not significant. DLMO, sleep-onset and age were most discriminated factors between the various CSRWDs. Estimation of DLMO is only possible in patients with ASWPD and in DSWPD patients with a regular sleep pattern.

Aims Phelan-McDermid syndrome (PMD) is a congenital syndrome caused by a deletion on chromosome 22q13.3. About 600 cases have been identified worldwide. PMD is characterized by neonatal hypotonia, moderate/severe intellectual impairment, impaired expressive language, and typical dysmorphic features. Psychological symptoms as hyperactivity, attention problems, restlessness, and stereotyped-repetitive behavior were reported. The aim of the study was to assess incontinence and associated psychological problems in PMD. Methods Forty-one individuals with PMD were recruited through a German support group (48.8% male; mean age 13.4 years; range, 4-55 years). Parents or caregivers completed the developmental behavior checklist (DBC), as well as the parental questionnaire: enuresis/urinary incontinence, including six questions on adaptive toileting skills. Results Rates of nocturnal enuresis (NE), daytime urinary incontinence, and fecal incontinence were 86%, 73%, and 79%. Rates were similar in all age groups (children, teens, adults). Constipation was present in 19%. Forty-two percent of the sample had a clinically relevant DBC score, with adults more affected than teens. Persons with NE had significantly higher "anxiety/depression" subscale scores. Toileting skills were more developed in adults than in children. Sixty-eight percent had further physical disabilities. Conclusions Incontinence rates in PMD are high in all age groups. However, persons with PMD can improve their toilet skills. Therefore, the assessment and treatment of incontinence in persons with PMD is recommended. Constipation does not seem to be a major problem in PMD. Due to the high prevalence rates of somatic conditions, an assessment for organic and functional incontinence is recommended.

BackgroundFetal Alcohol Spectrum Disorders (FASD) is an important global health problem in need of prevention. For FASD prevention it is important to understand why pregnant women engage or do not engage in drinking alcohol. It remains unknown which psychosocial determinants related to maternal alcohol consumption are most in need of prevention. The objective of this study was to identify these.MethodWe searched in PubMed, PsychINFO, PsychARTICLES, ERIC, CINAHL, EMBASE and MEDLINE databases up to May 2018 using an extensive query consisting of keywords related to pregnancy (e.g., maternal, prenatal), alcohol use (e.g., alcohol, drink) and determinants (e.g., attitude, norm). Studies were excluded when not published in English, were reviews, or involved non-human subjects. Substantial heterogeneity precluded aggregation or meta-analysis of the data. Instead, data were qualitatively inspected.ResultsA total of 23 studies including 150 identified items were eligible for data analysis. Studies covered over 15 psychosocial determinants (e.g., attitude, perceived social norm, risk perception). Studies differed in their operationalizations. As a majority of data was based on univariate analysis, little is known about the relationship with specific drinking behaviors. The majority of studies targeted perceived risk and motivation to comply with each social referents' approval or disapproval. A large proportion of studies focused on disadvantages and risks of maternal alcohol consumption. Results from these studies show that women do not continue to drink because the risks are unknown to them. Cautious interpretation is needed while the observed heterogeneity hindered firm conclusions. Conclusion We aimed to identify all relevant psychosocial determinants of maternal alcohol consumption behavior(s). The state of the literature precludes such conclusions. It remains unknown which determinants are most in need of intervention. It is recommended for future studies to (i) identify all possible psychosocial determinants of drinking during pregnancy using both quantitative and qualitative methods; (ii) include different target groups (e.g., women with unplanned pregnancies, pregnant women, women in childbearing age); (iii) identify key environmental agents; (iv) operationalize their measures based on theoretical models; (v) report specific variables such as the study method and association with behavior.

ObjectivesFetal alcohol spectrum disorders (FASD) is a worldwide problem. Maternal alcohol consumption is an important risk factor for FASD. It remains unknown which alcohol consumption patterns most strongly predict FASD. The objective of this study was to identify these.DesignSystematic literature review.MethodsWe searched in PubMed, PsychINFO, PsycARTICLES, ERIC, CINAHL, Embase and MEDLINE up to August 2018. The query consisted of keywords and their synonyms related to FASD, pregnancy and behaviour. Studies were excluded when not published in English, were reviews or involved non-human subjects. Substantial heterogeneity precluded aggregation or meta-analysis of the data. Instead, data were qualitatively inspected.ResultsIn total, 21 studies were eligible for further data analysis. All studies that measured both maternal alcohol drinking behaviours and FASD reported retrospective data on maternal drinking patterns, employing both continuous and categorical measures and exhibiting substantial heterogeneity in measures of alcohol consumption (eg, timing of exposure, quantification of alcohol measure and definition of a standard drink). Study quality improved over time and appeared higher for studies based on active case ascertainment, especially when conducted in schools and when behaviour was assessed through interviews.ConclusionsWe aimed to identify specific maternal drinking behaviour(s) related to FASD. The state of the literature precludes such conclusions. Evidence-based preventive measures necessitate identifying which prenatal alcohol drinking behaviour(s) are most in need of intervention. Therefore, we formulate three recommendations for future research. First, future studies can optimise the value of the collected dataset through specifying measurements and reporting of maternal drinking behaviours and avoiding categorised measures (nominal or ordinal) whenever possible. Second, samples should not be selected based on FASD status, but instead, FASD status as well as maternal alcohol consumption should both be measured in a general population sample. Finally, we provide 10 reporting guidelines for FASD research.

Introduction Individualized support planning (ISP) has become a key aspect of supports for people with ID and is mandated in several countries. Different stakeholders develop policies and expectations regarding ISP. In this study, we report on requirements as found in Dutch official ID policy and on the results of consultations of panels of stakeholders and experts working in the field of ID. It was intended to describe, summarize and discuss these requirements for the purpose of enhancing ISP practices. Method A combination of desk research of policy documents and consultation of two expert panels was performed. Results A variety of criteria on content, procedures, quality and person-centeredness of ISP is being used by different stakeholders. These criteria were described and summarized. Discussion The broad range of inconsistent requirements and sometimes conflicting expectations from different stakeholders hamper a clear conceptualization of ISP and affect the use of ISP in practice.

Fragile-X-syndrome (FXS) is caused by a mutation on the X chromosome (Xq27.3). Males with a full mutation have typical dysmorphic signs, moderate intellectual disability and psychological disorders. Twenty-five to fifty percent are affected by incontinence. The aim of the study was to assess subtypes of incontinence and psychological problems in children with FXS in their home environments. Twenty-two boys with FXS (mean age 11.0 years) and 22 healthy controls (mean age 11.1 years) were examined with sonography, uroflowmetry, 48-h bladder diary, physical examination, IQ test, parental psychiatric interview and questionnaires regarding incontinence and psychological symptoms in a home setting. Boys with FXS had higher rates of incontinence than controls (59.1 vs. 4.8 %). The most common subtypes in FXS boys were primary non-monosymptomatic nocturnal enuresis, urge incontinence and nonretentive faecal incontinence. 90.9 % boys with FXS had a psychological comorbidity. Incontinence and behavioural symptoms were not associated.Boys with FXS have a higher risk for physical disabilities, psychological disorders and incontinence than healthy boys. Constipation is not a major problem in FXS. As effective treatment is available for children with ID, we recommend offering assessment and therapy to all children with FXS and incontinence.• Boys with fragile-X-syndrome (FXS) have higher rates of incontinence, psychological disorders and somatic conditions than typically developing boys. What is New: • Constipation is a rare condition in FXS in contrast to other genetic syndromes. • Although incontinence rates are higher, urological findings (uroflowmetry, sonography) are not more pathological per se in FXS.

Background Not much is known about Do-Not-Attempt-Resuscitation (DNAR) decision-making for people with intellectual disabilities (IDs). The aim of this study was to clarify the problems and pitfalls of non-emergency DNAR decision-making for people with IDs, from the perspective of ID physicians. Methods This qualitative study was based on semi-structured individual interviews, focus group interviews and an expert meeting, all recorded digitally and transcribed verbatim. Forty ID physicians and trainees were interviewed about problems, pitfalls and dilemmas of DNAR decision-making for people with IDs in the Netherlands. Data were analysed using Grounded Theory procedures. Results The core category identified was ‘Patient-related considerations when issuing DNAR orders’. Within this category, medical considerations were the main contributory factor for the ID physicians. Evaluation of quality of life was left to the relatives and was sometimes a cause of conflicts between physicians and relatives. The category of ‘The decision-maker role’ was as important as that of ‘The decision procedure in an organisational context’. The procedure of issuing a non-emergency DNAR order and the embedding of this procedure in the health care organisation were important for the ID physicians. Conclusion The theory we developed clarifies that DNAR decision-making for people with IDs is complex and causes uncertainties. This theory offers a sound basis for training courses for physicians to deal with uncertainties regarding DNAR decision-making, as well as a method for advance care planning. Health care organisations are strongly advised to implement a procedure regarding DNAR decision-making.

Background: People with intellectual disabilities often present with unique challenges that make it more difficult to meet their palliative care needs. Aim: To define consensus norms for palliative care of people with intellectual disabilities in Europe. Design: Delphi study in four rounds: (1) a taskforce of 12 experts from seven European countries drafted the norms, based on available empirical knowledge and regional/national guidelines; (2) using an online survey, 34 experts from 18 European countries evaluated the draft norms, provided feedback and distributed the survey within their professional networks. Criteria for consensus were clearly defined; (3) modifications and recommendations were made by the taskforce; and (4) the European Association for Palliative Care reviewed and approved the final version. Setting and participants: Taskforce members: identified through international networking strategies. Expert panel: a purposive sample identified through taskforce members’ networks. Results: A total of 80 experts from 15 European countries evaluated 52 items within the following 13 norms: equity of access, communication, recognising the need for palliative care, assessment of total needs, symptom management, end-of-life decision making, involving those who matter, collaboration, support for family/carers, preparing for death, bereavement support, education/training and developing/managing services. None of the items scored less than 86% agreement, making a further round unnecessary. In light of respondents’ comments, several items were modified and one item was deleted. Conclusion: This White Paper presents the first guidance for clinical practice, policy and research related to palliative care for people with intellectual disabilities based on evidence and European consensus, setting a benchmark for changes in policy and practice.

Background Although fetal alcohol spectrum disorders (FASD) affect communities worldwide, little is known about its prevalence. The objective of this study was to provide an overview of the global FASD prevalence. Methods We performed a search in multiple electronic bibliographic databases up to August 2015, supplemented with the ascendancy and descendancy approach. Studies were considered when published in English, included human participants, and reported empirical data on prevalence or incidence estimates of FASD. Raw prevalence estimates were transformed using the Freeman–Tukey double arcsine transformation so that the data followed an approximately normal distribution. Once the pooled prevalence estimates, 95% confidence intervals and prediction intervals were calculated based on multiple meta-analyses with transformed proportions using random effects models, these estimates were transformed back to regular prevalence rates. Heterogeneity was tested using Cochran's Q and described using the I2 statistic. Results Among studies that estimated prevalence in general population samples, considerable differences in prevalence rates between countries were found and therefore separate meta-analyses for country were conducted. Particularly high-prevalence rates were observed in South Africa for fetal alcohol syndrome (55.42 per 1,000), for alcohol-related neurodevelopmental disorder (20.25 per 1,000), and FASD (113.22 per 1,000), For partial fetal alcohol syndrome high rates were found in Croatia (43.01 per 1,000), Italy (36.89 per 1,000), and South Africa (28.29 per 1,000). In the case of alcohol-related birth defects, a prevalence of 10.82 per 1,000 was found in Australia. However, studies into FASD exhibited substantial heterogeneity, which could only partly be explained by moderators, most notably geography and descent, in meta-regressions. In addition, the moderators were confounded, making conclusions as to each moderator's relevance tentative at best. Conclusions The worldwide pooled prevalence estimates are higher than assumed so far, but this was largely explained by geography and descent. Furthermore, prevalence studies varied considerably in terms of used methodology and methodological quality. The pooled estimates must therefore be interpreted with caution and for future research it is highly recommended to report methodology in a more comprehensive way. Finally, clear guidelines on assessing FASD prevalence are urgently needed, and a first step toward these guidelines is presented.

Little is known about the involvement of nurses in the process of making end-of-life decisions for people with intellectual disability (ID). The aim of this study was to clarify this process from the perspective of nurses. This qualitative study involved nine semistructured interviews with nurses working in chronic care, conducted after the deaths of patients with ID in the Netherlands. The interviews were transcribed verbatim and analyzed using Grounded Theory procedures. The core characteristic of the position of the nurses and of the way they supported the patient was Being at the center of communication. Related categories of topics emerging from the interviews were Having a complete picture of the patient, Balancing involvement and distance, Confidence in one's own opinion, and Knowledge about one's own responsibility, all of which were focused on the patient. This focus on the patient with ID might explain why the nurses could make valuable contributions to such an important subject as end-of-life decisions. People with ID themselves were not involved in the decisions. The nurses were not always aware who was ultimately responsible for the end-of-life decisions. Nurses are in a unique position to support the process of end-of-life decision-making. It is important to use their knowledge and give them a more prominent position in this decision-making process. It should be clear to all involved who is ultimately responsible for making the end-of-life decisions.

Background Goals and objectives as mentioned in Individual Support Plans (ISPs) were analysed to explore what domains of quality of life they are associated with, what support resources are referenced for achieving the goals, and how domains and resources are related to clients age, gender and intellectual disability (ID) level. Method A total of 209 ISPs for persons with ID from eight residential Dutch service provider organisations were analysed. Mixed linear regression analyses were conducted to examine the relations between client characteristics and the content of goals and support resources. Results Results showed that ISPs of people with mild and moderate ID had significantly more goals related to independence and social participation as compared to the ISPs of people with severe and profound ID. ISPs of clients with profound ID addressed quality of life factors related to ‘well-being’ more than ISPs of all other clients. ISPs of people aged 20–34 years had significantly more goals on independence than the two other age groups. ISPs of people under the age of 50 had significantly fewer goals with respect to well-being than found in ISPs of older people. Regarding the use of resources, 42.6% of the ISP goals were associated with resources from specialised services, 31.5% associated with natural resources and 25.9% associated with a combination of both natural and specialised services. In ISPs of people with mild ID, natural resources are more often mentioned, and specialised service-based resources are less often mentioned than for other people. Conclusions This study offers empirical feedback on ISP practices in the field of ID in the Netherlands. In light of current ISP practices, results suggest that attention should be paid to: (1) distinguishing between a ‘service contract’ and an ISP; (2) keeping a focus on the whole person in all age groups and levels of functioning and (3) involving the service recipient in ISP development and implementation.

Empirical research that addresses sexual orientation in people with an intellectual disability (ID) is limited, and very little is known regarding the personal experiences of lesbian and bisexual women with ID. This study set out to answer the question: What are the experiences of lesbian and bisexual women with a mild intellectual disability in the Netherlands? Ten lesbian and bisexual women (average age of 33 years) with a mild intellectual disability took part in our study comprising of semi-structured interviews. Participants reported that they had found it hard to talk to others about sensitive subjects such as their sexuality, and had been left to figure out information regarding their sexual orientation without support or guidance. Our results point to a lack of information, sexual education and role models when it comes to lesbian sex and women with an intellectual disability. Social contact was often limited, and participants experienced difficulties finding a partner. Furthermore, participants often had to cope with mental health problems and had struggled with loneliness, depression and addiction. Last but not least, our participants reported that they had been discriminated against. Coming out (revealing your sexual orientation) is not easy when you have an intellectual disability. To enable women with ID who have lesbian or bisexual feelings to understand and secure their sexual rights in their daily lives is important. Therefore, it is necessary to provide support in the following domains: sexual education and training, social contact and assertiveness.

Background Euthanasia and assisted suicide (EAS) have been legally possible in the Netherlands since 2001, provided that statutory due care criteria are met, including: (a) voluntary and well-considered request; (b) unbearable suffering without prospect of improvement; (c) informing the patient; (d) lack of a reasonable alternative; (e) independent second physician’s opinion. ‘Unbearable suffering’ must have a medical basis, either somatic or psychiatric, but there is no requirement of limited life expectancy. All EAS cases must be reported and are scrutinised by regional review committees (RTE). The purpose of this study was to investigate whether any particular difficulties arise when the EAS due care criteria are applied to patients with an intellectual disability and/or autism spectrum disorder. Methods The 416 case summaries available on the RTE website (2012–2016) were searched for intellectual disability (6) and autism spectrum disorder (3). Direct content analysis was used on these nine cases. Results Assessment of decisional capacity was mentioned in eight cases, but few details given; in two cases, there had been uncertainty or disagreement about capacity. Two patients had progressive somatic conditions. For most, suffering was due to an inability to cope with changing circumstances or increasing dependency; in several cases, suffering was described in terms of characteristics of living with an autism spectrum disorder, rather than an acquired medical condition. Some physicians struggled to understand the patient’s perspective. Treatment refusal was a common theme, leading physicians to conclude that EAS was the only remaining option. There was a lack of detail on social circumstances and how patients were informed about their prognosis. Conclusions Autonomy and decisional capacity are highly complex for patients with intellectual disabilities and difficult to assess; capacity tests in these cases did not appear sufficiently stringent. Assessment of suffering is particularly difficult for patients who have experienced life-long disability. The sometimes brief time frames and limited number of physician-patient meetings may not be sufficient to make a decision as serious as EAS. The Dutch EAS due care criteria are not easily applied to people with intellectual disabilities and/or autism spectrum disorder, and do not appear to act as adequate safeguards. Electronic supplementary material The online version of this article (10.1186/s12910-018-0257-6) contains supplementary material, which is available to authorized users.

Background: In patients with Prader-Willi syndrome (PWS) body composition is abnormal and alterations in appetite regulating factors, bone mineral density and insulin-like growth factor-1 (IGF-1) levels have been described. Studies in PWS adults are limited. In this study, we investigated body composition, appetite regulating peptides, bone mineral density and markers of bone remodeling in an adult PWS population. Furthermore, we investigated the association between these different parameters and IGF-1 levels because of the described similarities with growth hormone deficient patients.Methods: In this cross-sectional observational cohort study in a university hospital setting we studied fifteen adult PWS patients. Anthropometric and metabolic parameters, IGF-1 levels, bone mineral density and bone metabolism were evaluated. The homeostasis model assessment of insulin resistance (HOMA2-IR) was calculated. Fourteen healthy siblings served as a control group for part of the measurements.Results: In the adult PWS patients, height, fat free mass, IGF-1 and bone mineral content were significantly lower when compared to controls; body mass index (BMI), waist, waist-to-hip ratio and fat mass were higher. There was a high prevalence of osteopenia and osteoporosis in the PWS patients. Also, appetite regulating peptides and bone remodelling markers were aberrant when compared to reference values. Measurements of body composition were significantly correlated to appetite regulating peptides and high-sensitive C-reactive protein (hs-CRP), furthermore HOMA was correlated to BMI and adipokines.Conclusion: In adults with Prader-Willi syndrome alterations in body composition, adipokines, hs-CRP and bone mineral density were demonstrated but these were not associated with IGF-1 levels. Further investigations are warranted to gain more insight into the exact pathophysiology and the role of these alterations in the metabolic and cardiovascular complications seen in PWS, so these complications can be prevented or treated as early as possible.