The presence of problem behavior such as self-injury and aggression is a prominent and challenging feature of Cornelia de Lange syndrome (CdLS). Despite the growing body of research on behavior problems associated with behavioral phenotypes in genetic disorders, problem behavior in this population is not well understood. For example, individuals with CdLS are at high risk for developing self-jury, however it is not known why some do not develop this problem behavior. Additionally, few studies have examined environmental influences on problem behavior in CdLS. The field of applied behavior analysis (ABA) offers precise assessment methods that have led to an increased understanding of problem behavior, and improved treatment outcomes for individuals with intellectual and developmental disabilities (IDD). In particular, functional analysis procedures are considered the most rigorous method for determining what variables serve to maintain problem behavior; thereby, leading to the prescription of effective individualized treatments. However, there are only a few cases reported in the literature of functional analysis of problem behavior in CdLS. Preliminary findings from functional analyses and other assessments in CdLS indicate differences in forms of problem behavior, functions for problem behavior, and responsiveness to certain classes of stimuli, relative to other genetic disorders. Previous literature and preliminary data suggest that variables associated with certain genetic conditions may impact form, function, and responsiveness to treatment for problem behavior. Thus, the goals of this clinical trial are to 1) to identify key variables associated with problem behavior in CdLS by comparing children with and without problem behavior across multiple variables including language ability, stimulus preferences, emotion dysregulation, and presence of autism; and 2) evaluate the effectiveness of an outpatient model of ABA-based assessment and treatment for children with CdLS exhibiting problem behavior; and 3) follow children with CDLS without problem behavior over a period of 2 years to begin to obtain information about what variables lead to the emergence of problem behavior, and to apply early intervention strategies.
Individualized function-based treatments will be evaluated with each participant using single-case experimental designs. Assessment and treatment data from all participants will also be combined to evaluate program outcomes within a consecutive controlled case series design. This type of study design minimizes potential selection bias favoring positive outcomes by including all participants encountered regardless of outcome. All participants will complete standardized measures of preference, adaptive skills, problem behavior, ASD, and emotion dysregulation. Program outcomes will also be evaluated using statistical analysis methods with consultation from the Intellectual and Developmental Disabilities Research Center (IDDRC) Behavioral Phenotyping Core at the Kennedy Krieger Institute/Johns Hopkins University. Parent responses on study measures will be combined to evaluate satisfaction with treatment and with services.
Treatment Group
Pre-Visit Assessments
1. Parent will be asked to complete research measures at home including: Vineland Adaptive Behavior Scales (VABS-3) caregiver rating form, which is a standardized measure that provides developmental scores for communication skills, daily living skills, and socialization skills; Emotional Dysregulation Inventory (EDI) which is a caregiver-report questionnaire designed to capture emotional distress and problems with emotion regulation in both minimally verbal and verbal individuals; the Behavior Problem Inventory (BPI) which is a 49-item parent-completed instrument designed to measure the frequency and severity of a child's self-injurious, aggressive/destructive, and stereotypic behaviors; the Repetitive Behavior Scale-Revised (RBS-R), a 44-item inventory which measures the presence of repetitive and stereotypic behaviors in individual with ASD; the Aberrant Behavior Checklist (ABC), a 58-item inventory designed to measure a variety of emotional and behavior difficulties in individuals with IDD; and the Gilliam Autism Rating Scale: 2nd Edition (GARS). Completed measures will be mailed back to the study team.
2. Parent will be asked to provide any records or reports related to problem behavior including functional behavioral assessment, behavioral intervention plan, or behavioral data regarding previous or current behavioral services.
3. After parent returns measures by mail, a study team member will conduct a parent interview by phone to complete the Reinforcer Assessment Inventory for the Severely Disabled (RAISD); and the Functional Analysis Interview.
Study Visit at Kennedy Krieger Institute (KKI)/Day 1
1. For any child with self-injurious behavior (SIB), the team will administer the Self-Injury Trauma scale (SIT), which is designed to quantify the amount of tissue damage associated with SIB.
2. Conduct paired choice preference assessment to identify rank order of preferred stimuli that may be used in treatment.
3. Conduct a functional analysis to identify environmental variables maintaining child problem behavior. Sessions will be conducted in accordance with a standard protocol in use by the Neurobehavioral Unit Outpatient clinic (NBU OPC), including conditions that test for social functions of problem behavior. The study team will video-record these sessions.
Study Visit at KKI/Day 2
1. Study team and parent meet to discuss assessment findings and plan for treatment evaluation.
2. Conduct treatment evaluation of function-based intervention. Treatment options are within the standard of care in the NBU OPC. The study team will video-record these sessions.
3. Parent completes the Intervention Rating Profile-15, a 15-item measure of treatment acceptability.
4. Train parent to implement behavioral treatment, using standard procedures within the NBU OPC.
5. Parent completes the Intervention Rating Profile-15 and the Family Satisfaction Survey.
6. Follow-up phone call: (1 week post treatment) to assess child progress. The study team will also provide a brief summary of the child's preferred items /activities, and a summary of the results from the questionnaires the parent completed.
Study visit at KKI/Follow Up (2 weeks post treatment): During a 3-hour study visit, the continued effectiveness of the behavior plan and parent implementation of such will be assessed via direct observation of parent and child. The study team will video-record these sessions. Results will be reviewed with the family. Parents will also complete the ABC and BPI.
Follow-up phone calls at 4, 8, and 12 weeks post treatment. Refer for additional services if necessary.
Control Group
Once ages and adaptive functioning levels of treatment group participants are established, recruitment for matched controls will be initiated. Investigators will seek to identify children with CdLS between the ages of 3 and 15 years who do not exhibit self-injurious behavior, aggression, or disruptive behavior. Parents of potential participants will be asked to participate in 2 phone interviews. In the first phone interview, a parent will be asked a series of questions to rule out the presence of child problem behavior. Once it is determined that the child does not exhibit problem behavior, parents will be asked if they would like to participate in the study. After the family has consented, the study team will mail the VABS-3 for completion. If VABS-3 results match that of a treatment group participant, a second phone interview will be conducted to complete the RAISD. The BPI, ABC, RBS-R, GARS, and EDI will be mailed. Local families will be invited to attend a 2-hr clinic visit for preference assessments. To monitor for emergence of problem behavior in the control group, the BPI and EDI will be repeated every 3 months for up to 2 yrs. If such behavior does emerge, clinical services will be offered to the participant and family at no cost.
