Rationale: The STXBP1-Related Disorders (STXBP1-RD) are an ultra-rare, monogenic, developmental epileptic encephalopathy
with a complex phenotype. In clinic, caregivers often report behavioral difficulties as symptoms of ADHD and Autism. Although these behaviors can be very disruptive day-to-day, specific rates are not well defined. The Behavior Assessment Scale for Children – Third Edition (BASC-3) and Social Responsiveness Scale – 2
nd edition (SRS-2) are two “gold-standard” tools, though they have not been validated specifically in STXBP1-RD. The BASC-3 is a measure of internalizing and externalizing behaviors and other behavioral symptoms for ages 2 to 21-years-old. The SRS-2 is a measure of difficulties in social communication and amount of repetitive, restricted interests and behaviors (RRBs) for ages 2.5 to 18-years-old. The purpose of this study is to determine feasibility and face and content validity for use in STXBP1-RD.
Methods: All individuals completed comprehensive, clinical neuropsychological evaluations at Children’s Hospital Colorado, where behavioral data was collected using the BASC-3 and SRS-2. All participants consented for research via a protocol approved by COMIRB.
Results: For the BASC-3, data from 23 individuals with STXBP1-RD (mean age=9.5 years (SD=5.04), range from 2.17 to 21.92 years) were collected. One hundred percent of caregivers completed all questions. See Figure 1 for the distribution of T-scores across participants. Elevations, defined as a T-score greater-than-or-equal-to 65, were present for every behavioral concern except for anxiety, for which no concerns were raised. The highest frequency of concerns was raised for hyperactivity (48%), atypicality (48%), and attention problems (57%). Symptoms of withdrawal were also notable at 17% (see Table 1).
For the SRS-2, data from 11 individuals (mean age=9.25, SD=5.85) were collected. Once again, 100% of caregivers completed all questions. As shown in Figure 2, the distribution indicates that nearly all participants had elevated scores. The highest elevations (again at T >=65, see Table 2) were observed in terms of the presence of RRBs (64%) and difficulties with social awareness (64%) and social communication (82%). Interestingly, social motivation was a strength for these children.
Conclusions: This study provides evidence that the BASC-3 and SRS-2 capture the behavioral challenges in STXBP1-RD raised by parent report. We find elevated symptoms of attention problems, hyperactivity, and atypicality in around 50% of the sample. Behaviors often implicated in Autism are also endorsed, including difficulties with social communication, social awareness, and RRBs. Limitations include a small sample size. Elevations on either the BASC-3 or the SRS-2 are not diagnostic but may be used to prompt discussion and referral for further evaluation. Developmental level should always be considered when determining the degree to which behavioral problems are greater than expected. The BASC-3 and SRS-2 should be further validated in the STXBP1-RD population.
Funding: This work was supported by the STXBP1 Foundation.