Sleep disturbances correlate with behavioral problems among individuals with Wiedemann-Steiner syndrome

Abstract

Wiedemann-Steiner syndrome (WSS) is a rare genetic disorder caused by mutation in KMT2A and characterized by neurodevelopmental delay. This study is the first prospective investigation to examine the sleep and behavioral phenotypes among those with WSS through parent-informant screening inventories. A total of 24 parents of children/adults with WSS (11F, Mean age = 12.71 years, SD = 8.17) completed the Strengths and Difficulties Questionnaire (SDQ) and 22 of these caregivers also completed the Modified Simonds and Parraga Sleep Questionnaire (MSPSQ). On average, the majority of those with WSS (83%) were rated to show borderline to clinical level of behavioral difficulties on the SDQ. Approximately 83% were rated in these ranges for hyperactivity, 63% for emotional problems, and 50% for conduct problems. When applying prior published clinical cut-off for risk of sleep disturbance among those with neurodevelopmental disorders, over 80% of our sample exceeded this limit on the MSPSQ. Largely, caregivers’ ratings suggested restless sleep, rigid bedtime rituals, sleep reluctance and breathing through the mouth in sleep were most consistent problems observed. Partial correlations between sleep and behavioral domains showed elevated emotional problems were associated with parasomnia characteristics after controlling for age. Daytime drowsiness and activity were associated with more hyperactivity. Those with more night waking problems and delayed sleep onset were rated to show more severe conduct problems. Overall, these findings suggest dysfunctional sleep behaviors, hyperactivity, and affective problems are part of the neurobehavioral phenotype of WSS. Routine clinical care for those affected by WSS should include close monitoring of sleep and overactive behaviors.

Attention challenges in Kabuki syndrome

“…For example, individuals with Sotos syndrome, caused by heterozygous loss of function of NSD1, a histone methyltransferase like KMT2D, commonly display autism spectrum disorder, ADHD, anxiety and aggression (Lane et al 2016). Individuals with Wiedemann-Steiner syndrome, caused by heterozygous loss of function of KMT2A, another histone methyltransferase, present with elevated rates of anxiety, ADHD and aggression (Durand et al 2022;Ng et al 2023b). In a review of a single clinic population of individuals with MDEMs including KS, ADHD was one of the most common features (Harris et al 2023).…”

“…2022; Ng et al . 2023b). In a review of a single clinic population of individuals with MDEMs including KS, ADHD was one of the most common features (Harris et al .…”

Epigenetics of cognition and behavior: insights from Mendelian disorders of epigenetic machinery

“…Those with WSS present with elevated rates of anxiety [75,78,85] and behaviors concerning for ADHD [78,85]. In contrast to the low levels of aggression seen in those with KS [80][81][82], relatively high rates of aggression [75] and conduct problems have been reported among those with WSS [85][86][87] which may be due to poorer executive functioning skills [85][86][87].…”

“…Rates of autism spectrum disorder in WSS vary widely across case studies given different clinical sample sizes and types of assessments used to determine diagnostic classification [75,85,88], although new evidence highlights similar high sociability and strong prosocial skills in those affected regardless of diagnosis of intellectual disability or autism spectrum disorder [88,89]. In brief, KS and WSS are neurogenetic disorders with some common neuropsychological characteristics that may be reflective of shared disease-causing pathways which can be considered for future development of clinical trials.…”