Behavioral and neuropsychiatric challenges across the lifespan in individuals with Rubinstein-Taybi syndrome

Abstract

Introduction: Rubinstein-Taybi syndrome (RSTS) is a rare congenital disorder characterized by developmental and intellectual disability, broadening of thumbs and halluces, and characteristic facial features. Pathogenic variants in CREBBP lead to RSTS type 1 (RSTS1) and in EP300 lead to RSTS type 2 (RSTS2). Individuals with RSTS can demonstrate a variety of behavioral and neuropsychiatric challenges, including anxiety, hyperactivity/inattention, self-injury, repetitive behaviors, and aggression. Behavioral challenges are consistently reported as one of the primary factors impacting quality of life. Despite the high prevalence and morbidity of behavioral and neuropsychiatric features of RSTS, a paucity of data exists regarding its natural history. Methods: To better understand the neurocognitive and behavioral challenges faced by individuals with RSTS, 71 caregivers of individuals with RSTS, ranging in age from one to 61 years, completed four questionnaires measuring obsessive compulsive disorder (OCD)-like symptoms, anxiety, challenging behaviors, and adaptive behavior and living skills. Results: Results revealed a high prevalence of neuropsychiatric and behavioral challenges across ages. We found specific challenging behaviors were worse in school age individuals. Scaled adaptive behavior and living skill scores differed across ages with an increased gap between typically developing peers becoming more apparent at older ages. Between types, individuals with RSTS2 had better adaptive behavior and living skills and less stereotypic behaviors but higher social phobia than individuals with RSTS1. Further, female individuals with RSTS1 appear to have increased hyperactivity. However, both groups had impairments in adaptive functioning compared to typically developing peers. Discussion: Our findings support and expand previous reports of a high prevalence of neuropsychiatric and behavioral challenges in individuals with RSTS. However, we are the first to report differences between types of RSTS. Further, age-related differences were seen with higher challenging behaviors within school-age individuals, which may improve over time, and lower adaptive behavioral skills compared to normative scales. Anticipation of these potential differential challenges across age is vital for proactive management for individuals with RSTS. Our study underscores the importance of enacting neuropsychiatric and behavioral screening earlier in childhood so appropriate management can be implemented. However, further longitudinal studies in larger cohorts are needed to understand better how behavioral and neuropsychiatric characteristics of RSTS evolve over the lifespan and differentially affect subpopulation groups.

Keywords: Rubinstein-Taybi syndrome; adaptive living skills; age-related change; anxiety; behavior; epigenetic; obsessive compulsive disorder.

FIGURE 1

Neurobehavioral Phenotype of RSTS Sample. (A) Neuropsychological characteristics represented in our sample including intellectual and developmental disability (IDD), gross motor delay (GMD), fine motor delay (FMD), speech and language delay (SLD), autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD). (B) Breakdown of psychiatric diagnoses in our sample including obsessive compulsive disorder (OCD), disruptive mood dysregulation disorder (DMDD), and oppositional defiant disorder (ODD).

FIGURE 2

Challenging Behaviors across Age and between Age Groups. (A) Stereotypic behavior decreases across age. All data points are included for data visualization, but age regression analysis was performed with only validated ages. (B) Stereotypic behaviors and hyperactivity/noncompliance are highest in school age children. Asterisks represent statistical significance (*p < 0.050; **p < 0.010; ***p < 0.001).

FIGURE 3

Adaptive Behavior and Living Skills between Age Groups. (A) Adaptive Behavior Composite standard scores (SS) are lowest in adults. (B) Communication and Daily Living Skills domain SS are lowest in adults. (C) Coping skills subdomain v-scale scores (VS.) are lower in individuals of school age, adolescence/early adulthood, and adulthood compared to early childhood individuals. Asterisks represent statistical significance (*p < 0.050; **p < 0.010; ***p < 0.001).

FIGURE 4

Communication and Daily Living Skills across Age. (A) Receptive and Expressive language raw scores (RS) are higher among individuals of older age while written language skills were lower in older ages. (B) Personal, Domestic, and Community skills RS increase across age. The black trendline represents the overall trend across all 3 cohorts.

FIGURE 5

Adaptive Behavior and Living Skills between Individuals with RSTS1 and RSTS2. (A) Individuals with RSTS2 have higher social phobia than individuals with RSTS1. (B–C) Adaptive Behavior Composite and Communication and Daily Living Skills domain standard scores (SS) were lower in individuals with RSTS1. (D–F) Across the depicted subdomains, v-scale scores (VS.) were lower in individuals with RSTS1. Asterisks represent statistical significance (*p < 0.05; **p < 0.01; ***p < 0.001).

FIGURE 6

Daily Living Skills between RSTS Types and Based on Age. Individuals with RSTS2 have higher daily living skills between school age and adolescence/early adulthood than individuals with RSTS1 of the same age. Asterisks represent statistical significance (*p < 0.05; **p < 0.01; ***p < 0.001).

FIGURE 7

Challenging Behaviors between RSTS Types and Based on Sex. Females with RSTS1 experienced more hyperactivity/noncompliance than females with RSTS2. Asterisks represent statistical significance (**p < 0.01).