Simons VIP Phenotyping: What we ve learned so far Ellen Hanson, Ph.D. and Raphael Bernier, Ph.D. Family Meeting Summer, 2015
Outline Brief review of data collection procedures Discussion of Neurodevelopmental and Psychiatric Disorders Cognitive profiles Summary of other disorders Longitudinal Study Phase II Study Future Directions *N s may change throughout
What is Phenotyping in Simons VIP? Phenotyping simply refers to the documentation of observable characteristics or traits of an organism In practice, however, this can become slightly more complicated
Family Flow Recruitment Core Emory Phenotyping Cores Children s Hospital, Boston Texas Children s, Houston UW Seattle 2 nd Level Imaging Cores UCSF CHOP Screening Medical records Multiple day visits All family members Neurocognitive Testing MRI Feedback 2 days Additional neurocognitive measures fmri, MEG
Assessment Measures Diagnostic Assessment - ADI-R and ADI-T - ADOS/ADOS-T - BAPQ - SCQ - SRS/SRS-ARV - ABCL/CBCL - DISC/DISC-YC - SCL-90 Motor - Purdue Pegboard - Movement ABC-II Language - CASL -MCDI - CCC-2 -OSEL - CTOPP -CELF* History - Education History Interview -Intervention History Interview -Previous Diagnosis Interview Executive Function - DKEFS* Adaptive Behaviors - Vineland - PSI Parental Stress Medical* - DAS-II - Mullen - WASI Cognitive Learning/Achievement - WIAT Repetitive Behaviors - BSIQ * Measures done at UCSF and CHOP or Emory
Phenotyping: What are we testing for? Simons VIP looked at a wide range of disorders, but particularly at neurodevelopmental and psychiatric disorders
Family members as comparison We used the extensive testing data that was completed by family members to try to understand which areas of strengths and difficulties tended to run in families and which were more likely to be related to the deletion or duplication Family members data, particularly from siblings, is often very helpful for comparison. This is because they have many of the same genes and are raised in a similar environment and things like cognitive ability tend to be similar in brothers and sisters
What Are Neurodevelopmental Disorders? A group of conditions with an onset in the developmental period, often before a child enters grade school Produce impairments of personal, social, academic or occupational functioning Refer to a wide range of issues very specific limitations of learning or control of executive functions to global impairments of social skills or intelligence. Often frequently co-occur (more than one at a time)
Types of Neurodevelopmental Disorders Intellectual Disability/Cognitive Ability Learning Disorders Motor Skills Disorder/Developmental Coordination Disorder Communication Disorders Autism Spectrum Disorders ADHD and Disruptive Behavior Disorders Tic Disorders
Types of Psychiatric Disorders These can be a bit trickier to diagnose in younger children Diagnoses that may be seen or start in the childhood period include things like Anxiety, Mood Disorders and Depression Also includes diagnoses such as Schizophrenia which is not usually seen until early adulthood
Rates of Neurodevelopmental and Psychiatric Disorders in individuals with 1611.2 del and dup The following slide shows the percent of individuals who were given a diagnosis, meaning that they were having enough difficulty in a specific area that it was associated with significant distress or disability There were other children who may have had some symptoms but didn t meet criteria for the diagnosis (continuum)
Diagnostic Profile: 16p11.2 Deletion 70 60 16p11.2 deletion child carriers (n = 110) Non-carrier siblings (n =66 ) 64 % 61 % 50 45 % Percentage 40 30 24 % 24 % 20 10 14 % 8 % 11 % 14 % 5 % 0
Diagnostic Profile: 16p11.2 Deletion 16 4 n=70 8 15 7 12 8
Diagnostic Profile: 16p11.2 Duplication 60 16p11.2 duplication child carriers (n = 58) Non-carrier siblings (n = 23) 50 Percentage 40 30 20 12 (21%) 10 (17%) 10 (17%) 23 (40%) 12 (21%) 23 (40%) 9 (16%) 10 4 (7%) 2 (3%) 5 (9%) 2 (3%) 0
Diagnostic Profile: 16p11.2 Duplication 4 n=41 2 1 3 12 8 11
What is Intellectual or Cognitive Ability? Also called General Intelligence The ability to think about ideas, analyze situations, and solve problems It is measured through various types of intelligence tests Usually separated into Verbal Intelligence Nonverbal Intelligence
Cognitive Profile in 16p11.2 deletion and duplication syndrome Cognitive challenges across verbal and nonverbal domains. But substantial variability. Performance below the mean (average of the population) and below family member performance. Similar challenges in other cognitive-related areas daily living skills (i.e. taking care of yourself cooking, dressing etc). specific school tasks such as reading and math.
Cognitive Ability: 16p11.2 Deletion and Duplication vs Non-Carrier 140 120 16p11.2 deletion child carrier (n = 110) 16p11.2 duplication child carrier (n=66) Non-carrier siblings (n = 106) 106 103 106.5 100 80 85.5 80 89 76 85 93 60 40 20 0 Full Scale IQ Non-verbal IQ Verbal IQ
Summary of 16p11.2 Duplication and Deletion Cases Duplication Full Scale IQ 80 86 One or more DSM Dx 80% 95% ASD 20% 24% Most Frequent Dx Intellectual Disability DCD ADHD ASD Deletion Speech Sound Disorder DCD Language Disorders Mean Raw BSIQ Total 13.1 8.7
Behavior and Sensory Interests Questionnaire (BSIQ) Individuals with 16p11.2 deletion and duplication have also been found to have higher rates of repetitive and restrictive behaviors and sensory interests (RRB s). Examples include flapping and lining up items as well as being overly interested in the sight, feel smell or taste of items. Simons VIP used a new measure, the BSIQ to measure these behaviors as well as helped to finalize the standardization of this measure. The final measure and paper will be out this summer.
BSIQ Children with ASD vs. Non-ASD with 16p11.2 Duplication 70 Child Non-ASD (n=11) 80 Child ASD (n=4) 60 70 67 67 % of total Behaviors 50 40 30 45 36 36 36 36 % of total Behaviors 60 50 40 30 50 50 50 20 20 10 10 0 Adverse to loud noises Delayed echolalia Difficulties with changes in daily routine Interest in sensory stimuli Line up objects 0 Immediate echolalia Delayed echolalia Difficulties Interest in Line up objects with changes sensory stimuli in daily routine
90 80 BSIQ Children with ASD vs. Non-ASD with 16p11.2 Deletion Top 5 most endorsed behaviors Child Non-ASD (n = 25) 90 86 80 Child ASD (n = 7) 70 70 60 56 60 57 57 57 % of total behaviors 50 40 30 44 40 32 32 % of total Behaviors 50 40 30 43 20 20 10 10 0 Adverse to loud noises Pushing face Difficulties Difficulties with changes inwith changes in school schedule Inspect objects out of corner of eyes 0 Adverse to loud noises Difficulties with changes in school Limited food choices Interest in sensory stimuli Pushing face
Challenging Behaviors Behavioral challenges increase with language impairments, cognitive deficits and neurodevelopmental disorders. Behavioral challenges can significantly impact quality of life Potential Resources: Expert support: Psychologists with expertise in neurodevelopmental disorders Experts with behavioral therapies, applied behavioral analysis Books: The Explosive Child (Greene) Your Defiant Child: 8 Steps to Better Behavior (Barkley) Your Defiant Teen (Barkley & Robin)
Longitudinal Study As part of Simons-VIP we re also following many families with young children over time. This data is still preliminary Looks at growth in cognitive ability over time Seeing gains across both domains of cognitive functioning (verbal and nonverbal) with strong gains in verbal abilities Hope to see continued closing of the gap between children with 16p11.2 del and dup and their peers with appropriate, intensive intervention
Longitudinal Study of Children 54 families enrolled and young children are followed longitudinally Cognitive Ability
PHASE 1 Simons VIP Phase 2 Online www.simonsvipconnect.org Register Site Visit PHASE 2 A portal to direct participation Register At home: 4 surveys per person + phone call 2.5 hours Annual followup Reach more families, more flexible, annual follow-up of developmental changes, and study results provided
Phase 2 Process Register Account Setup Consent Surveys
Take Home Points Children with the del and dup are at higher risk for wide range and level of developmental issues Early assessment is essential Early, intensive intervention is best Parents have to be advocates for services Issues and interventions may change as children age Regular re-assessment for children with concerns is vital
Future Directions Best Practice for clinical psychological and medical evaluation of individuals diagnosed with 16p11.2 deletion and duplication More analysis to thoroughly understand current data Longitudinal studies to understand course of development Phase Two On-Line follow up of families
Thank YOU for your time, energy and commitment to helping understand 16p11.2 deletion and duplication syndrome