Rea Hannah M, Webb Sara Jane, Kurtz-Nelson Evangeline C, Hudac Caitlin M, Bernier Raphael A, Miles Conor, Earl Rachel, Whiting Alana, Eayrs Curtis, Johansson Margaret, Wang Tianyun, Eichler Evan E, Neuhaus Emily
Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, United States.
Seattle Children's Research Institute, Center on Child Health, Behavior and Development, Seattle, WA, United States.
Front Neurosci. 2025 Jan 7;18:1485499. doi: 10.3389/fnins.2024.1485499. eCollection 2024.
, a protein kinase located on human chromosome 21, plays a role in postembryonic neuronal development and degeneration. Alterations to have been consistently associated with cognitive functioning and neurodevelopmental disorders (e.g., autism, intellectual disability). However, the broader cognitive and behavioral phenotype of syndrome requires further characterization. Specifically, executive functioning, or cognitive processes that are necessary for goal-directed behavior, has not yet been characterized in this population.
Individuals with variants ( = 29; ages 4 to 21 years) were assessed with a standardized protocol with multiple measures of executive functioning: Delis-Kaplan Executive Function Schedule, and chronologically age-appropriate caregiver-report forms of the Behavior Rating Inventory of Executive Function (BRIEF) and Achenbach System of Empirically Based Assessment (ASEBA). We first examined the feasibility and appropriateness of established executive functioning measures among participants with syndrome to inform selection of executive functioning tools in future research. We then characterized executive functioning among the group, including associations with other phenotypic features.
Neurocognitive assessments of executive functioning were deemed infeasible due to cognitive and verbal functioning. Caregiver-report revealed elevated executive functioning concerns related to self-monitoring, working memory, and planning/organization on the BRIEF, and attention and ADHD on the CBCL. Only two participants had existing ADHD diagnoses; however, 5 participants (out of 10 participants with data) exceeded the cutoff on the BRIEF, 13 individuals (out of 27 with data) exceeded the cutoff on the ASEBA ADHD subscale, and 18 exceeded the cutoff on the ASEBA attention subscale. There was concordance between ADHD diagnosis and the ASEBA, but not BRIEF. Executive functioning was correlated with nonverbal IQ and autism traits.
Objective measures of executive functioning are needed for individuals with intellectual disability who are nonverbal and/or have motor limitations. Diagnostic overshadowing, or the tendency to attribute all problems to intellectual disability and to leave other co-existing conditions, such as executive functioning challenges or ADHD, undiagnosed, is common. Phenotypic characterization of executive functioning is therefore important for our understanding of syndrome and for ensuring that caregivers' concerns are addressed, and individuals receive the clinical services that best meet their needs.
[某种蛋白质激酶]位于人类21号染色体上，在胚胎后期神经元发育和退化过程中发挥作用。该蛋白质激酶的改变一直与认知功能和神经发育障碍（如自闭症、智力残疾）相关。然而，[该蛋白质激酶相关]综合征更广泛的认知和行为表型需要进一步明确。具体而言，执行功能，即目标导向行为所需的认知过程，在这一人群中尚未得到明确。
对携带[该蛋白质激酶]变异的个体（n = 29；年龄4至21岁）采用标准化方案进行评估，该方案包含多种执行功能测量方法：德利斯-卡普兰执行功能量表，以及按年龄顺序适配的照顾者报告形式的执行功能行为评定量表（BRIEF）和基于经验的评估阿肯巴克系统（ASEBA）。我们首先检验了在[该蛋白质激酶相关]综合征参与者中既定执行功能测量方法的可行性和适用性，以为未来研究中执行功能工具的选择提供参考。然后我们明确了该组人群的执行功能特征，包括与其他表型特征的关联。
由于认知和语言功能原因，对执行功能的神经认知评估被认为不可行。照顾者报告显示，在BRIEF量表上，与自我监控、工作记忆和计划/组织相关的执行功能问题有所增加，在儿童行为检查表（CBCL）上，注意力和多动症方面的问题有所增加。只有两名参与者已有多动症诊断；然而，5名参与者（在有数据的10名参与者中）超过了BRIEF量表的临界值，13名个体（在有数据的27名个体中）超过了ASEBA多动症分量表的临界值，18名个体超过了ASEBA注意力分量表的临界值。多动症诊断与ASEBA量表结果一致，但与BRIEF量表结果不一致。执行功能与非言语智商和自闭症特征相关。
对于存在语言障碍和/或运动受限的智力残疾个体，需要客观的执行功能测量方法。诊断掩盖现象，即将所有问题都归因于智力残疾，而使其他并存状况（如执行功能挑战或多动症）未被诊断出来的倾向很常见。因此，执行功能的表型特征对于我们理解[该蛋白质激酶相关]综合征以及确保照顾者的担忧得到解决、个体获得最符合其需求的临床服务而言非常重要。
