Here is a summary of a paper recently published out of the Journal of Autism and Developmental Disorders titled “Adaptive Skills of Individuals with Angelman Syndrome Assessed Using the Vineland Adaptive Behavior Scales, 2nd Edition.” This exciting work is from the long-standing Angelman syndrome Natural History Study that started in 2006, thanks to so many families that participated over the years. Thank you to FAST for providing funding for analyzing this important work and the Angelman Syndrome Biomarker and Outcome Measure Consortium (ABOM) for their support in ensuring this work gets published for the benefit of upcoming and ongoing clinical trials.
This study allowed for a closer look at the journey of adaptive skills in Angelman syndrome and how this information is being utilized in both a clinical and clinical trial setting. The Vineland Adaptive Behavior Scales (VABS) is one of the most frequently used assessment tools measuring skills in those living with neurodevelopmental disorders, though it has significant limitations since it was designed for a neurotypical developing individual. This assessment is ideally performed through an interview with a trained neuropsychologist, and it focuses on the activity domains of communication, daily living skills, socialization and motor function. This measure has been adapted over time by the developer and throughout the AS Natural history study the version used was the VABS-II (2006-2019) the VABS-II to an improved 3rd version (VABS-III) from 2019 to the present. The VABS-III is currently being utilized in all of the ongoing clinical trials with an aim to measure changes in adaptive skills over time.
In this new publication, a team of AS researchers, including Drs. Angela Gwaltney, Sarah Nelson Potter, Anjali Sadhwani, and Anne Wheeler, took an in-depth look at the adaptive skills of individuals living with Angelman syndrome (AS) pertaining to these areas of interest over time. The study examined the developmental trajectory of adaptive skills in 257 individuals aged 1 to 13, encompassing all genotypes of AS using the (VABS-II). Prior research has indicated that those with AS experience substantial delays in adaptive skills, however previous studies have lacked an understanding of how these skills evolve over time and are limited due to their small sample sizes. The primary objective of this study was to provide a comprehensive characterization of adaptive skills across different AS genotypes by analyzing data from the Vineland-II collected at a minimum of three timepoints during the course of the NHS. This is a very important need for understanding change overtime after a potential meaningful therapeutic.
The VABS-II is an assessment that measures skills in key areas of importance to AS individuals and their caregivers: communication, daily living skills, socialization, and motor skills (gross and fine motor). This tool helps to document where our loved ones are thriving, where they may need more support, and what the natural trajectory of skill acquisition is over time. This is important for therapeutics being tested in clinical trials. By showing a clear change from the baseline trajectory of skill acquisition, companies and clinicians can better understand if a drug is working.
The VABS assesses communication skills including expressive, receptive, and written subdomains. Daily living skills are split into three subdomains of:
personal (independence in activities like dressing, eating, washing, etc.)
domestic (household tasks like food preparation)
community (functioning outside the home, e.g., traveling, safety, etc.)
Socialization is also subdivided into three categories including:
interpersonal relationships (how one interacts with others)
play and leisure time (engagement with others in play and leisure activities)
coping skills (response to interpersonal situations)
Motor skills are evaluated assessing both gross motor (coordination and movement of limbs and torso) and fine motor (precise muscle movements, e.g., hand movements) assessments.
The 257 individuals that participated in the study had a genotype distribution as follows: 26% had Class I deletion, 40% had Class II deletion, 15% had mutations, and 19% were classified as ICD/UPD cases.
The findings confirm that delays in adaptive skills are significant, but what’s more compelling is how these skills vary across different genotypes and how they develop, or fail to develop, over time. All of those living with AS exhibited substantial delays in adaptive skill development, regardless of genotype when compared to neurotypical peers. While deletion cases had lower scores than their non-deletion counterparts, with some overlap, the difference is minimized when compared to their age matched neurotypical peers. These differences seem somewhat marginal when the big picture of adaptive skills are assessed, but when a clinical trial is being designed, these differences in genotype are important because these differences, which are meaningful to families and caregivers, might potentially be captured, and change might be appreciated. Since the intent is to see how far the needle can shift over a short period of time within the confines of a clinical trial, this baseline difference, built around genotypes, helps more accurately gauge where the different starting points are and to ensure trials are as homogeneous as possible for these assessments.
Here is a summary of the paper:
item 1For daily living skills, communication, socialization assessment, gross and fine motor skills all genotypes were impacted, with the deletion genotype (Class I and II) being statistically more impacted than those with non-deletion genotypes. Compared to neurotypical age-matched peers the difference in all genotypes was significantly different.
Individuals living with AS exhibited progressive improvement in all adaptive skill metrics over time, even through their early adolescent years. This underscores the significance of providing services that support the ongoing enhancement and retention of these acquired abilities at all ages.
This data supported their capabilities to learn new skills and progress over time. Something as caregivers we all know, but standardized tests often don’t show. Their acquisition of skills is incredibly delayed, but they continue to gain skills in many areas of adaptive functioning well into adolescence, and adulthood (though this paper does not capture adult ages).
This study isn’t just numbers and charts; it’s a deeper understanding of our loved one’s unique abilities and needs. By recognizing the differences in adaptive skills between genotypes, we are one step closer to personalized interventions and strategies that can truly make a difference in our loved ones lives, while also being more careful as we design trials and try to measure these specific changes over time. It also serves as the first comprehensive report of significant adaptive skill development across all VABS-II domains.
Here is where it matters the most – an understanding of adaptive skills in AS, the genotype-specific measurements, and the expected developmental trajectory is crucial when formulating interventional strategies and designing clinical trials. Measuring improvements in adaptive skills is part of understanding the steps toward a gain of independence. There is nothing we all want more for our loved ones living with AS than to become more independent over time.