Qu'd Dima, Schmitt Lauren M, Leston Amber, Harris Jacqueline R, Slavotinek Anne, Riddle Ilka, Brightman Diana S, Simpson Brittany N
Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
Front Genet. 2023 Jun 21;14:1116919. doi: 10.3389/fgene.2023.1116919. eCollection 2023.
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 lead to RSTS type 1 (RSTS1) and in 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. 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 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. 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.
鲁宾斯坦-泰比综合征（RSTS）是一种罕见的先天性疾病，其特征为发育和智力残疾、拇指和拇趾增宽以及具有特征性的面部特征。CREBBP基因的致病变异导致1型鲁宾斯坦-泰比综合征（RSTS1），而EP300基因的致病变异导致2型鲁宾斯坦-泰比综合征（RSTS2）。患有RSTS的个体可能会表现出各种行为和神经精神方面的挑战，包括焦虑、多动/注意力不集中、自我伤害、重复行为和攻击行为。行为挑战一直被报告为影响生活质量的主要因素之一。尽管RSTS的行为和神经精神特征具有较高的患病率和发病率，但关于其自然病史的数据却很少。为了更好地了解RSTS患者所面临的神经认知和行为挑战，71名年龄在1岁至61岁之间的RSTS患者的照料者完成了四份问卷，这些问卷用于测量强迫症（OCD）样症状、焦虑、挑战性行为以及适应性行为和生活技能。结果显示，各年龄段的神经精神和行为挑战患病率都很高。我们发现特定的挑战性行为在学龄期个体中更为严重。适应性行为和生活技能的量表得分在不同年龄段有所不同，随着年龄增长，与正常发育的同龄人之间的差距越来越明显。在不同类型之间，RSTS2患者的适应性行为和生活技能更好，刻板行为更少，但社交恐惧症比RSTS1患者更高。此外，RSTS1的女性患者似乎多动症状更严重。然而，与正常发育的同龄人相比，两组患者在适应性功能方面都存在损害。我们的研究结果支持并扩展了之前关于RSTS患者中神经精神和行为挑战患病率较高的报告。然而，我们是第一个报告RSTS不同类型之间差异的研究。此外，我们发现了与年龄相关的差异，学龄期个体的挑战性行为更高，随着时间推移可能会有所改善，与标准量表相比，适应性行为技能更低。预期这些不同年龄阶段潜在的差异挑战对于RSTS患者的积极管理至关重要。我们的研究强调了在儿童早期进行神经精神和行为筛查的重要性，以便能够实施适当的管理。然而，需要在更大规模队列中进行进一步的纵向研究，以更好地了解RSTS的行为和神经精神特征在整个生命周期中如何演变以及如何不同地影响亚人群组。
