Consensus recommendations on mental health issues in Phelan-McDermid syndrome.

Phelan-McDermid syndrome is a rare genetic condition caused by a deletion encompassing the 22q13.3 region or a pathogenic variant of the gene SHANK3. The clinical presentation is variable, but main characteristics include global developmental delay/intellectual disability (ID), marked speech impairment or delay, along with other features like hypotonia and somatic or psychiatric comorbidities. This publication delineates mental health, developmental and behavioural themes across the lifetime of individuals with PMS as informed by parents/caregivers, experts, and other key professionals involved in PMS care. We put forward several recommendations based on the available literature concerning mental health and behaviour in PMS. Additionally, this article aims to improve our awareness of the importance of considering developmental level of the individual with PMS when assessing mental health and behavioural issues. Understanding how the discrepancy between developmental level and chronological age may impact concerning behaviours offers insight into the meaning of those behaviours and informs care for individuals with PMS, enabling clinicians to address unmet (mental health) care needs and improve quality of life.

Consensus recommendations on communication, language and speech in Phelan-McDermid syndrome.

Phelan-McDermid syndrome is a genetic condition primarily caused by a deletion on the 22q13.3 region or a likely pathogenic/pathogenic variant of SHANK3. The main features comprise global developmental delay, marked impairment or absence of speech, and other clinical characteristics to a variable degree, such as hypotonia or psychiatric comorbidities. A set of clinical guidelines for health professionals covering relevant aspects of clinical management have been written by the European PMS Consortium, and consensus has been reached regarding final recommendations. In this work, attention is given to communication, language and speech impairments in PMS, and the findings from available literature are presented. Findings from the literature review reveal marked speech impairment in up to 88% of deletions and 70% of SHANK3 variants. Absence of speech is frequent and affects 50%-80% of the individuals with PMS. Communicative skills in the expressive domain other than spoken language remain understudied, but some studies offer data on non-verbal language or the use of alternative/augmentative communication support. Loss of language and other developmental skills is reported in around 40% of individuals, with variable course. Deletion size and possibly other clinical variables (e.g., conductive hearing problems, neurological issues, intellectual disability, etc.) are related to communicative and linguistic abilities. Recommendations include regular medical check-ups of hearing and the assessment of other factors influencing communication, thorough evaluation of preverbal and verbal communicative skills, early intervention, and support via alternative/augmentative communication systems.

Speech and Language in 5-year-olds with Different Neurological Disabilities and the Association between Early and Later Consonant Production.

The primary aim was to describe speech and language abilities in a clinical group of verbal 5-year-old children diagnosed with neurological disability (ND) in infancy, and the secondary aim was to trace precursors to consonant production at age 5 years (T2) in data from 12 to 22 months (T1). The participants (n = 11, with Down syndrome (DS), cerebral palsy, and chromosomal deletion syndromes) were tested with a battery of speech and language tests. Consonant production at T2 was compared to data on consonant use at T1. At T2, two participants had age appropriate speech and language and another three had age-appropriate speech, but low results on language tests. The remaining six participants had severe speech and language difficulties. Participants with DS had significantly lower results on consonant production measures. An association between consonant production at T1 and T2 for participants with DS indicates that number of different true consonants might be a predictive measure when evaluating young children with DS.

'More than a box of puzzles': Understanding the parental experience of having a child with a rare genetic condition".

BACKGROUND: Chromosomal microarray (CMA) testing has been adopted as the first-tier diagnostic test for developmental disabilities. However, determining the clinical significance of the results is often complex. This qualitative study seeks to explore parental interpretation, adaption and coping in the context of ambiguous rare genetic findings in order to support parental adjustment and wellbeing. METHODS: In-depth interviews were conducted with parents (n = 30) of children identified with a rare genetic chromosomal abnormality. RESULTS: Three major themes were identified following a thematic analysis: 'Learning of the Genetic Diagnosis', "The Reality of the Rarity' and 'Beyond Genetics: The Child Takes Centre Stage'. Findings demonstrated that parental adjustment to their child's genetic results are mediated by several factors including child difficulties and stage of development, clinician communication, perception of genetics, intrinsic coping strategies, access to practical and emotional support as well as broader contextual experiences. CONCLUSION: This study highlights the importance of considering the parental perspective in the context of genetic testing in clinical practice.

Recent developments in Phelan-McDermid syndrome research: an update on cognitive development, communication and psychiatric disorders.

PURPOSE OF REVIEW: The purpose of this review is to summarize the literature on cognitive development, communication, behavioral or psychiatric aspects in Phelan-McDermid syndrome (PMS) and to discuss the clinical implications and recommendations of these summarized findings. RECENT FINDINGS: PMS is often associated with severe communication impairments, behavioral or psychiatric problems and regression. These challenges may adversely affect and impair the quality of life of the individual with PMS and his family. SUMMARY: Individuals with PMS experience intellectual disability, communication and behavioral/psychiatric challenges, such as catatonia, bipolar disorder and regression across the lifespan. Providing appropriate guidance and support to them and their families demands a better understanding of these challenges.

Psychometric Study of the Social Responsiveness Scale in Phelan-McDermid Syndrome.

The Social Responsiveness Scale-2 (SRS-2) is a quantitative measure used to characterize symptoms of autism spectrum disorder (ASD). However, research suggests that SRS-2 scores are significantly influenced by language ability and intellectual disability (ID). Efforts to refine the SRS-2 by Sturm, Kuhfeld, Kasari, and Mccracken [Journal of Child Psychology and Psychiatry, 58(9), 1053-1061] yielded a shortened form, yet its psychometric properties in populations with severe ID remain unknown. This study aims to examine the psychometric properties of the SRS-2 in Phelan-McDermid syndrome (PMS), a genetic condition associated with ASD and ID, thereby guiding score interpretation in this population and future development of targeted scales. Analyses, including Item Response Theory (IRT), were conducted on a sample of individuals with PMS (n = 91) recruited at six sites nationally. Psychometric properties evaluated include measures of reliability (internal consistency, test-retest reliability) and validity (structural, construct, content). While both SRS-2 forms are reliable, the shortened SRS-2 shows superior validity to the full SRS-2 for measuring ASD symptoms in PMS. On IRT analysis, the shortened SRS-2 shows excellent discrimination and precisely evaluates respondents across a wide range of ASD symptomatology but interpretation is limited by uncertain content validity and small sample size. The shortened SRS-2 shows some promise for use in PMS, but future refinements and additions are needed to develop items that are tailored to identify ASD in children with severe ID and specifically PMS. LAY SUMMARY: This study determined that a shortened form of the Social Responsiveness Scale, Second Edition (SRS-2) shows both promise and limitations for the characterization of autism symptomatology in individuals with Phelan-McDermid syndrome (PMS), a population characterized by intellectual disability (ID). Caution should be used when interpreting SRS-2 scores in individuals with ID and future research should modify existing items and develop new items to improve the SRS-2's ability to accurately characterize autism symptomatology in PMS. Autism Res 2020, 13: 1383-1396. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

Who ever heard of 16p11.2 deletion syndrome? Parents' perspectives on a susceptibility copy number variation syndrome.

Chromosomal microarray analysis is an important diagnostic tool to identify copy number variations (CNV). Some of the CNVs affect susceptibility regions, which means that deletions or duplications in these regions have partial penetrance and often give an increased risk for a spectrum of neurocognitive disorders. Not much is known about the impact of rare CNV susceptibility syndromes on the life of patients or their parents. In this study, we focus on one specific susceptibility CNV disorder, 16p11.2 deletion syndrome. This rare condition is characterised by an increased risk of mild intellectual disability, autism spectrum disorder, epilepsy, and obesity. We aimed to explore the impact of such a disorder on the family members involved in the daily care of children with this syndrome. Three focus group discussions were held with 23 Dutch (grand)parents. Thematic analysis was performed by two independent researchers. The following five themes emerged: (1) the end of a diagnostic odyssey and response to the diagnosis, (2) after the diagnosis-life with a child with 16p11.2 deletion syndrome, (3) access to medical care and support services, (4) nobody knows what 16p11.2 deletion syndrome is, and (5) future perspective-ideal care. The participants experienced a lack of knowledge among involved professionals. Together with the large variability of the syndrome, this led to fragmented care and unfulfilled needs regarding healthcare, social, and/or educational assistance. Care for children with a CNV susceptibility syndrome could be improved by a multidisciplinary approach or central healthcare professional, providing education and information for all involved professionals.

Family experiences and attitudes about receiving the diagnosis of sex chromosome aneuploidy in a child.

The most common sex chromosome aneuploidies (SCA) (47, XXY; 47, XYY; 47, XXX) frequently result in a milder phenotype than autosomal aneuploidies. Nevertheless, these conditions are highly variable and more symptomatic phenotypes may require significant clinical involvement, including specialty care. While historically most individuals with mild phenotypes remained undiagnosed during their lifetime, the increasing use of genetic testing in clinical care has increased the prenatal and postnatal diagnosis of SCAs. These genetic tests are frequently ordered by nongenetic providers who are also responsible for delivering the diagnosis. We surveyed parents of children (n = 308) to evaluate their experience of receiving a diagnosis and their support needs. The majority (73.3%) received the diagnosis from a nongenetic medical provider. Following a prenatal diagnosis parents reported experiencing depression, anxiety, and less optimism than those receiving a postnatal diagnosis. Few parents reported receiving materials explaining their child's condition that they found to be up-to-date, accurate, and unbiased. The frequently negative reported experiences of parents at time of diagnosis suggests more educational opportunities should be provided for nongenetic providers in order to become more informed about these conditions and communicate the diagnosis in a way parents experience as supportive.

Psychiatric illness and regression in individuals with Phelan-McDermid syndrome.

BACKGROUND: Phelan-McDermid syndrome (PMS) is a genetic condition characterized by intellectual disability, speech and language deficits, hypotonia, autism spectrum disorder, and epilepsy. PMS is caused by 22q13.33 deletions or mutations affecting SHANK3, which codes for a critical scaffolding protein in excitatory synapses. SHANK3 variants are also known to be associated with an increased risk for regression, as well as for psychiatric disorders, including bipolar disorder and catatonia. This study aimed to further describe these phenomena in PMS and to explore any relationship between psychiatric illness and regression after early childhood. METHODS: Thirty-eight people with PMS were recruited to this study through the Phelan-McDermid Syndrome Foundation based on caregiver report of distinct development of psychiatric symptoms. Caregivers completed a clinician-administered semi-structured interview focused on eliciting psychiatric symptomatology. Data from the PMS International Registry were used to confirm genetic diagnoses of participants and to provide a larger sample for comparison. RESULTS: The mean age of the 38 participants was 24.7 years (range = 13 to 50; SD = 10.06). Females (31 of 38 cases; 82%) and sequence variants (15 of 38 cases; 39%) were over-represented in this sample, compared to base rates in the PMS International Registry. Onset of psychiatric symptoms occurred at a mean age of 15.4 years (range = 7 to 32), with presentations marked by prominent disturbances of mood. Enduring substantial loss of functional skills after onset of psychiatric changes was seen in 25 cases (66%). Symptomst indicative of catatonia occurred in 20 cases (53%). Triggers included infections, changes in hormonal status, and stressful life events. CONCLUSIONS: This study confirms that individuals with PMS are at risk of developing severe neuropsychiatric illness in adolescence or early adulthood, including bipolar disorder, catatonia, and lasting regression of skills. These findings should increase the awareness of these phenotypes and lead to earlier diagnosis and the implementation of appropriate interventions. Our findings also highlight the importance of genetic testing in the work-up of individuals with intellectual disability and acute psychiatric illness or regression. Future research is needed to clarify the prevalence and nature of psychiatric disorders and regression among larger unbiased samples of individuals with PMS.

Incontinence and psychological symptoms in Phelan-McDermid syndrome.

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.

[Cat-eye syndrome (a psychiatric aspect)]. / Sindrom 'koshach'ikh glaz' (psikhiatricheskii aspekt).

Cat-eye syndrome is associated with abnormalities in chromosome 22. Based on the literature on genetic and clinical characteristics of the disease, three clinical cases observed by the authors at different times are analyzed. Mental retardation of different degree was observed in all cases and schizotypal personality disorder in one case. The latter case is described in detail. The patient's stress due to the mockery of peers and teenagers regarding the characteristics of the patient's features plays a considerable role in the exacerbation of mental illness. Early cosmetic surgical intervention (iris's coloboma removal) is necessary to prevent exacerbations of a mental illness and comfortable existence of the patient in the social environment.

Neuropsychiatric decompensation in adolescents and adults with Phelan-McDermid syndrome: a systematic review of the literature.

Phelan-McDermid syndrome (PMS) is caused by haploinsufficiency of the SHANK3 gene on chromosome 22q13.33 and is characterized by intellectual disability, hypotonia, severe speech impairments, and autism spectrum disorder. Emerging evidence indicates that there are changes over time in the phenotype observed in individuals with PMS, including severe neuropsychiatric symptoms and loss of skills occurring in adolescence and adulthood. To gain further insight into these phenomena and to better understand the long-term course of the disorder, we conducted a systematic literature review and identified 56 PMS cases showing signs of behavioral and neurologic decompensation in adolescence or adulthood (30 females, 25 males, 1 gender unknown). Clinical presentations included features of bipolar disorder, catatonia, psychosis, and loss of skills, occurring at a mean age of 20 years. There were no apparent sex differences in the rates of these disorders except for catatonia, which appeared to be more frequent in females (13 females, 3 males). Reports of individuals with point mutations in SHANK3 exhibiting neuropsychiatric decompensation and loss of skills demonstrate that loss of one copy of SHANK3 is sufficient to cause these manifestations. In the majority of cases, no apparent cause could be identified; in others, symptoms appeared after acute events, such as infections, prolonged or particularly intense seizures, or changes in the individual's environment. Several individuals had a progressive neurological deterioration, including one with juvenile onset metachromatic leukodystrophy, a severe demyelinating disorder caused by recessive mutations in the ARSA gene in 22q13.33. These reports provide insights into treatment options that have proven helpful in some cases, and are reviewed herein. Our survey highlights how little is currently known about neuropsychiatric presentations and loss of skills in PMS and underscores the importance of studying the natural history in individuals with PMS, including both cross-sectional and long-term longitudinal analyses. Clearer delineation of these neuropsychiatric symptoms will contribute to their recognition and prompt management and will also help uncover the underlying biological mechanisms, potentially leading to improved interventions.

Attitudes Toward Hypothetical Uses of Gene-Editing Technologies in Parents of People with Autosomal Aneuploidies.

Researchers are exploring the use of gene-editing technologies to prevent and/or treat genetic conditions in humans. Stakeholder views, including those of patient and family populations, are important in the ongoing bioethical discussion. We conducted 27 semi-structured interviews with parents of people with trisomy 21 (T21; N = 10), trisomy 18 (T18; N = 8), and trisomy 13 (T13; N = 9)-conditions not previously studied in regard to attitudes toward hypothetical gene editing. While many discussions focus on the morality of gene editing, parents in our study focused on quality of life and concerns about changing their children's identity. All participants prioritized ameliorating life-threatening health issues when those were present; many also emphasized increasing their children's communication and cognitive ability. These results suggest that patient populations with the lived experience of genetic conditions have unique concerns that may differ from broader discourse.

Sensorimotor Cortical Oscillations during Movement Preparation in 16p11.2 Deletion Carriers.

Sensorimotor deficits are prevalent in many neurodevelopmental disorders like autism, including one of its common genetic etiologies, a 600 kb reciprocal deletion/duplication at 16p11.2. We have previously shown that copy number variations of 16p11.2 impact regional brain volume, white matter integrity, and early sensory responses in auditory cortex. Here, we test the hypothesis that abnormal cortical neurophysiology is present when genes in the 16p11.2 region are haploinsufficient, and in humans that this in turn may account for behavioral deficits specific to deletion carriers. We examine sensorimotor cortical network activity in males and females with 16p11.2 deletions compared with both typically developing individuals, and those with duplications of 16p11.2, using magnetoencephalographic imaging during preparation of overt speech or hand movements in tasks designed to be easy for all participants. In deletion carriers, modulation of beta oscillations (12-30 Hz) were increased during both movement types over effector-specific regions of motor cortices compared with typically developing individuals or duplication carriers, with no task-related performance differences between cohorts, even when corrected for their own cognitive and sensorimotor deficits. Reduced left hemispheric language specialization was observed in deletion carriers but not in duplication carriers. Neural activity over sensorimotor cortices in deletion carriers was linearly related to clinical measures of speech and motor impairment. These findings link insufficient copy number repeats at 16p11.2 to excessive neural activity (e.g., increased beta oscillations) in motor cortical networks for speech and hand motor control. These results have significant implications for understanding the neural basis of autism and related neurodevelopmental disorders.SIGNIFICANCE STATEMENT The recurrent ∼600 kb deletion at 16p11.2 (BP4-BP5) is one of the most common genetic etiologies of ASD and, more generally, of neurodevelopmental disorders. Here, we use high-resolution magnetoencephalographic imaging (MEG-I) to define with millisecond precision the underlying neurophysiological signature of motor impairments for individuals with 16p11.2 deletions. We identify significant increases in beta (12-30 Hz) suppression in sensorimotor cortices related to performance during speech and hand movement tasks. These findings not only provide a neurophysiological phenotype for the clinical presentation of this genetic deletion, but also guide our understanding of how genetic variation encodes for neural oscillatory dynamics.

Intellectual, adaptive and behavioural characteristics in four patients with 18p deletion syndrome.

BACKGROUND: The association of behavioural phenotype assessment with cytogenomic characterisation may provide a better comprehension of genotype-phenotype correlations in syndromes caused by chromosomal abnormalities, such as 18p deletion syndrome. METHOD: We report on four Brazilian patients with 18p deletion syndrome characterised by cytogenomic techniques and detailed neuropsychological evaluation. Intellectual, adaptive and behavioural characteristics were assessed through the Wechsler's Scales, the Vineland-II Scale and the Child Behaviour Checklist, respectively. Socio-economic measures including main caretaker educational level and family income as defined by Brazilian criteria for social class classification were also collected to evaluate a possible contribution of environmental factors in neurocognitive variability. RESULTS: Two out of four patients showed intellectual disability (IQ < 70). Wechsler's scale results suggest that in our sample, interpretation of social situations based on observation of non-verbal behaviour constitute a cognitive strength while judgement of social rules and language skills associated with word knowledge and verbal fluency may be a cognitive weakness. Concerning adaptive behaviour, motor and socialisation domains showed to better develop than communication and daily living skills on the Vineland-II Scale. Only one patient presented internalising behavioural problems based on the Child Behaviour Checklist. Our results also suggested that socio-economic status may contribute to overall patient development. CONCLUSION: Our results suggest that some 18p deletion syndrome patients may present average intellectual performance and that the segment deletion size and some families' socio-economic conditions may influence cognitive development.

Blurring boundaries. Interviews with PGT couples about comprehensive chromosome screening.

OBJECTIVE: Comprehensive chromosome examination is a promising approach to Preimplantation Genetic Testing (PGT). Next to testing of specific chromosomes, such as in the case of reduced fertility due to chromosomal translocations, it allows testing of all chromosomes. Hence it potentially reduces the time to pregnancy and the risk of miscarriage. But comprehensive testing also introduces some ethical issues. For example, what is the role of the professional in the decision making regarding embryos with chromosomal abnormalities that are potentially viable? Which chromosomal abnormalities should be communicated to people undergoing fertility treatment? With this paper we wanted to explore the ethical issues related to comprehensive chromosome screening in Preimplantation Genetic Testing. DESIGN: In order to explore these issues, we interviewed seven couples undergoing PGT for chromosomal translocations at the VUB University Hospital, Belgium. We presented them with three fictional cases: the transfer of an embryo with trisomy 21, of an embryo with a sex chromosome aneuploidy and of an embryo with a chromosomal microdeletion. RESULTS: We found that opinions regarding the role of fertility professionals in deciding which embryos to transfer were mixed. Moreover, where to draw the line between healthy and unhealthy embryos was unclear. We also found that couples, although they thought that comprehensive chromosome testing had certain benefits, also considered the increased waiting time for transfer a heavy burden. CONCLUSIONS: In the light of comprehensive chromosome screening of embryos, persons undergoing fertility treatment may have views on the burdens and benefits of the techniques that are not analogous to the views of professionals.

Phelan-McDermid syndrome in adult patient with atypical bipolar psychosis repeatedly triggered by febrility.

Phelan-McDermid syndrome (PMD) is a rare genetic condition with only a few cases describing patients diagnosed as adults. We describe a long diagnostic odyssey of a 30-year-old woman who was diagnosed with Phelan-McDermid syndrom. Array comparative genomic hybridization analysis confirmed a 22q13.33 deletion, encompassing exon 9-23 of the SHANK3 gene and exon 1 of the ACR gene. We provide an uncommon feature of the disease, where psychotic alteration is repeatedly triggered by the same physical factor in our patient - mild fever episodes.

Clinician vs. Machine: Estimating Vocalizations Rates in Young Children With Developmental Disorders.

Purpose: The purpose of this study was to investigate the reliability of an automated language analysis system, the Language Environment Analysis (LENA), compared with a human transcriber to determine the rate of child vocalizations during recording sessions that were significantly shorter than recommended for the automated device. Method: Participants were 6 nonverbal male children between the ages of 28 and 46 months. Two children had autism diagnoses, 2 had Down syndrome, 1 had a chromosomal deletion, and 1 had developmental delay. Participants were recorded by the LENA digital language processor during 14 play-based interactions with a responsive adult. Rate of child vocalizations during each of the 84 recordings was determined by both a human transcriber and the LENA software. Results: A statistically significant difference between the 2 methods was observed for 4 of the 6 participants. Effect sizes were moderate to large. Variation in syllable structure did not explain the difference between the 2 methods. Vocalization rates from the 2 methods were highly correlated for 5 of the 6 participants. Conclusions: Estimates of vocalization rates from nonverbal children produced by the LENA system differed from human transcription during sessions that were substantially shorter than the recommended recording length. These results confirm the recommendation of the LENA Foundation to record sessions of at least 1 hr.

Study protocol for The Emory 3q29 Project: evaluation of neurodevelopmental, psychiatric, and medical symptoms in 3q29 deletion syndrome.

BACKGROUND: 3q29 deletion syndrome is caused by a recurrent hemizygous 1.6 Mb deletion on the long arm of chromosome 3. The syndrome is rare (1 in 30,000 individuals) and is associated with mild to moderate intellectual disability, increased risk for autism and anxiety, and a 40-fold increased risk for schizophrenia, along with a host of physical manifestations. However, the disorder is poorly characterized, the range of manifestations is not well described, and the underlying molecular mechanism is not understood. We designed the Emory 3q29 Project to document the range of neurodevelopmental and psychiatric manifestations associated with 3q29 deletion syndrome. We will also create a biobank of samples from our 3q29 deletion carriers for mechanistic studies, which will be a publicly-available resource for qualified investigators. The ultimate goals of our study are three-fold: first, to improve management and treatment of 3q29 deletion syndrome. Second, to uncover the molecular mechanism of the disorder. Third, to enable cross-disorder comparison with other rare genetic syndromes associated with neuropsychiatric phenotypes. METHODS: We will ascertain study subjects, age 6 and older, from our existing registry ( 3q29deletion.org ). Participants and their families will travel to Atlanta, GA for phenotypic assessments, with particular emphasis on evaluation of anxiety, cognitive ability, autism symptomatology, and risk for psychosis via prodromal symptoms and syndromes. Evaluations will be performed using standardized instruments. Structural, diffusion, and resting-state functional MRI data will be collected from eligible study participants. We will also collect blood from the 3q29 deletion carrier and participating family members, to be banked at the NIMH Repository and Genomics Resource (NRGR). DISCUSSION: The study of 3q29 deletion has the potential to transform our understanding of complex disease. Study of individuals with the deletion may provide insights into long term care and management of the disorder. Our project describes the protocol for a prospective study of the behavioral and clinical phenotype associated with 3q29 deletion syndrome. The paradigm described here could easily be adapted to study additional CNV or single gene disorders with high risk for neuropsychiatric phenotypes, and/or transferred to other study sites, providing a means for data harmonization and cross-disorder analysis.

Profile of women choosing the Harmony® Prenatal Test.

INTRODUCTION: The Harmony® Prenatal Test, a noninvasive cell-free DNA (cfDNA) method for major trisomies has been available since January 2013 at our unit, and tests were sent to the Ariosa Clinical Laboratory Improvement Amendments (CLIA) laboratory in California. From July 2017 onward, prenatal cfDNA has been reimbursed in Belgium for all pregnancies; however, since then samples are sent to a local laboratory. Little data are available on patient's profile and choices toward cfDNA and on the performance of local technology transfer centers. Areas covered: The profiles and choices of women regarding this test were evaluated. Further, the performance of cfDNA at the local laboratory was compared to the one in California. Our results showed that women from the Netherlands, as compared to Belgium, were more likely to undergo cfDNA testing for maternal request and would be less likely to undergo karyotyping if cfDNA were unavailable, therefore are better candidates for cfDNA testing, when this is used as first-line screening. Expert commentary: Our findings highlight the importance of conducting these types of studies, before decisions about clinical implementation are made by national governments and ministries of health.