Global developmental delay and a de novo deletion of the 16p13.13 region.

Many rare genetic variants are associated with the risk of atypical neurodevelopmental trajectories. In this study, we report a patient with developmental delay, autistic traits and multiple congenital anomalies, including congenital heart anomalies and orofacial cleft, with a 0.832 Mb de novo deletion of the 16p13.13 region classified as a variant of uncertain significance. Comparison of similar sized deletions and duplications overlapping the same genes in the DECIPHER database, revealed seven reports of copy number variants (CNVs), four duplications and three deletions. A neurodevelopmental phenotype including learning disability and intellectual disability was noted in some of the DECIPHER entries where phenotype was provided. Although the association between a deletion in this region and an atypical neurodevelopmental trajectory remains to be elucidated, the overlapping CNVs with neurodevelopmental phenotypes suggests possible candidate genes within the 16p13.13 region.

Support to caregivers who have received genetic information about neurodevelopmental and psychiatric vulnerability in their young children: A narrative review.

Diagnosis of pathogenic genetic variants associated with neurodevelopmental and psychiatric disorders (NPDs) is increasingly made early in life. This narrative review focuses on the need for, and provision of, psychological supports following genetic diagnosis. We conducted a literature search of publications on how caregivers are informed about the NPD vulnerability associated with genetic variants, challenges and unmet needs when receiving this information, and whether psychological supports are provided. Given its early recognition, the 22q11.2 deletion has been studied thoroughly for two decades, providing generalizable insights. This literature indicates the complex caregivers' needs related to learning about potential NPD vulnerabilities associated with a genetic variant, include how to communicate the diagnosis, how to identify early signs of NPDs, how to deal with stigma and a lack of medical expertise outside of specialized genetics clinics. With one exception, no publications describe psychotherapeutic support provided to parents. In the absence of support, caregivers struggle with several unmet needs regarding potential longer-term NPD implications of a genetic diagnosis. The field needs to go beyond explaining genetic diagnoses and associated vulnerabilities, and develop approaches to support caregivers with communicating and managing NPD implications across the child's lifespan.

A multidisciplinary approach and consensus statement to establish standards of care for Angelman syndrome.

BACKGROUND: Angelman syndrome (AS) is a rare neurogenetic disorder present in approximately 1/12,000 individuals and characterized by developmental delay, cognitive impairment, motor dysfunction, seizures, gastrointestinal concerns, and abnormal electroencephalographic background. AS is caused by absent expression of the paternally imprinted gene UBE3A in the central nervous system. Disparities in the management of AS are a major problem in preparing for precision therapies and occur even in patients with access to experts and recognized clinics. AS patients receive care based on collective provider experience due to limited evidence-based literature. We present a consensus statement and comprehensive literature review that proposes a standard of care practices for the management of AS at a critical time when therapeutics to alter the natural history of the disease are on the horizon. METHODS: We compiled the key recognized clinical features of AS based on consensus from a team of specialists managing patients with AS. Working groups were established to address each focus area with committees comprised of providers who manage >5 individuals. Committees developed management guidelines for their area of expertise. These were compiled into a final document to provide a framework for standardizing management. Evidence from the medical literature was also comprehensively reviewed. RESULTS: Areas covered by working groups in the consensus document include genetics, developmental medicine, psychology, general health concerns, neurology (including movement disorders), sleep, psychiatry, orthopedics, ophthalmology, communication, early intervention and therapies, and caregiver health. Working groups created frameworks, including flowcharts and tables, to help with quick access for providers. Data from the literature were incorporated to ensure providers had review of experiential versus evidence-based care guidelines. CONCLUSION: Standards of care in the management of AS are keys to ensure optimal care at a critical time when new disease-modifying therapies are emerging. This document is a framework for providers of all familiarity levels.

The role of the behavior analyst on interprofessional mental health teams: opportunities for collaboration and enhancing patient care.

Patients living with mental illness have needs that span a range of professional disciplines, settings, and service systems. These needs are best addressed through interprofessional collaboration. Behavior analysts can play a valuable role in enhancing patient care as part of the interprofessional mental health team. We provide information about the field of applied behavior analysis and its contribution to the assessment and treatment of patients living with mental health and substance use challenges. We outline how behavior analysts are trained and touch upon the practice of behavior analysis in North America and beyond. We describe collaborative relationships with other mental health professionals and, as an example, review the role of the behavior analyst on interprofessional teams in our mental health and addiction teaching hospital in Canada. We highlight some of the challenges faced by behavior analysts working in the mental health field and offer suggestions to increase their profile and opportunities for collaboration in clinical programs.

Supporting Children With Neurodevelopmental Disorders During the COVID-19 Pandemic.

Families of children with neurodevelopmental disorders are especially vulnerable during the COVID-19 pandemic. Physical distancing requirements and closure of schools and services in the context of the COVID-19 pandemic are likely challenging to everyone but may be particularly impactful for families with children with neurodevelopmental disorders ([NDDs], eg, intellectual disability, attention-deficit/hyperactivity disorder [ADHD], autism spectrum disorder [ASD]). Although a small number of children may experience less stress or anxiety due to reduced social and academic expectations,1 for many children with NDDs, and particularly those with ASD, carefully developed behavioral and environmental supports, and consistent and predictable routines and expectations, are vital for their mental well-being.2 Consequently, abrupt discontinuation of these supports during quarantine and prolonged isolation creates a real risk for behavioral exacerbations in this vulnerable population.3-6 Possible consequences for family members include physical and mental strain,7 whereas for the child with an NDD, increased emotional distress and challenging behavior may create safety concerns and the need for hospitalization.4,6 Children with NDDs may be at increased risk for COVID and COVID-related complications,8 emphasizing the need for preventive and/or crisis behavioral health care availability outside of emergency and hospital settings.

A novel intronic variant in UBE3A identified by genome sequencing in a patient with an atypical presentation of Angelman syndrome.

Angelman syndrome (AS) is a genetic neurodevelopmental disorder caused by loss or deficient expression of UBE3A on the maternally inherited allele. In 10-15% of individuals with a clinical diagnosis of AS, a molecular diagnosis cannot be established with conventional testing. We describe a 13-year-old male with an atypical presentation of AS, who was found to have a novel, maternally inherited, intronic variant in UBE3A (c.3-12T>A) using genome sequencing (GS). Targeted sequencing of RNA isolated from blood confirmed the creation of a new acceptor splice site. These GS results ended a six-year diagnostic odyssey and revealed a 50% recurrence risk for the unaffected parents. This case illustrates a previously unreported splicing variant causing AS. Intronic variants identifiable by GS may account for a proportion of individuals who are suspected of having well-known genetic disorders despite negative prior genetic testing.

Using Behavioral Approaches to Assess Memory, Imitation and Motor Performance in Children with Angelman Syndrome: Results of a Pilot Study.

Purpose: This study was designed to assess memory, imitation of motor actions and motor performance by 12 children (age range 40-151 months) with Angelman syndrome (AS), a rare neurogenetic disorder associated with learning and memory impairments. Methods: Children's functioning was assessed at several time points over a 3-month period. Results: Memory and motor performance tests had acceptable test-retest and inter-rater reliability whereas the motor imitation test did not. Children were able to recall action sequences after a 24-h delay. Memory and motor performance scores were correlated with children's chronological age and raw scores on subdomains of the Vineland-II. Conclusions: These behavioral tests require further development and evaluation but may show promise to accompany standardized assessments that are currently in use with children with AS.

Self-Injury in Autism Spectrum Disorder and Intellectual Disability: Exploring the Role of Reactivity to Pain and Sensory Input.

This paper provides information about the prevalence and topography of self-injurious behavior in children and adults with autism spectrum disorder and intellectual disability. Dominant models regarding the etiology of self-injury in this population are reviewed, with a focus on the role of reactivity to pain and sensory input. Neuroimaging studies are presented and suggestions are offered for future research.

Neurodevelopmental outcomes in children with Angelman syndrome after 1 year of behavioural intervention.

OBJECTIVE: To examine the impact of teaching approaches based on the principles of applied behaviour analysis (ABA) on neurodevelopmental outcomes in children with Angelman syndrome (AS). METHODS: A non-randomized pre-test-post-test control group design was used. The intervention group consisted of four children with AS aged 3.1-9.2 years. Controls were other children with AS who were individually matched on the basis of chronological age, gender and molecular sub-type. Children in the intervention group were provided two-to-three ABA-based therapy sessions per week over a 1-year period. Standardized measures of cognitive, adaptive and language functioning were administered at baseline and after 1 year. RESULTS: There were no statistically significant differences between the two groups at baseline or after 1 year. However, positive trends were observed in the intervention group for some cognitive and adaptive measures. CONCLUSION: ABA-based intervention improved aspects of neurodevelopment for some children with AS and warrants further study.

Angelman syndrome 2005: updated consensus for diagnostic criteria.

In 1995, a consensus statement was published for the purpose of summarizing the salient clinical features of Angelman syndrome (AS) to assist the clinician in making a timely and accurate diagnosis. Considering the scientific advances made in the last 10 years, it is necessary now to review the validity of the original consensus criteria. As in the original consensus project, the methodology used for this review was to convene a group of scientists and clinicians, with experience in AS, to develop a concise consensus statement, supported by scientific publications where appropriate. It is hoped that this revised consensus document will facilitate further clinical study of individuals with proven AS, and assist in the evaluation of those who appear to have clinical features of AS but have normal laboratory diagnostic testing.

Comparing rates of psychiatric and behavior disorders in adolescents and young adults with severe intellectual disability with and without autism.

Eight males and four females with an Autism Diagnostic Interview-Revised (ADI-R) diagnosis of autism (mean age of 16.3 years) and severe intellectual disability (IQ < 40) were individually matched to controls on the basis of chronological age, gender, and nonverbal IQ. The dependent measure was the Diagnostic Assessment for the Severely Handicapped-II, which is used to screen for psychiatric and behavior disorders in lower-functioning individuals. Participants with autism showed significantly greater disturbances as measured by the Diagnostic Assessment for the Severely Handicapped-II total score and seven of 13 subscales. They also averaged 5.25 clinically significant disturbances compared with 1.25 disturbances for participants without autism. Specific vulnerabilities to anxiety, mood, sleep, organic syndromes, and stereotypies/ tics were found in the participants with comorbid autism.