Sleep Problem Profiles of Individuals with ASD-Associated Mutations

Thursday, May 14, 2015: 5:30 PM-7:00 PM
Imperial Ballroom (Grand America Hotel)
R. K. Earl1, C. M. Hudac1, T. Ward2, J. Gerdts1, E. E. Eichler3 and R. Bernier1, (1)University of Washington, Seattle, WA, (2)Clinical Psychology, Seattle Pacific University, Seattle, WA, (3)Howard Hughes Medical Institute, Seattle, WA

Classifying ASD phenotypes by recurrent gene disrupting mutations has promise as an effective means of identifying potential subtypes of the disorder (Bernier et al, 2014). Sleep difficulties, such as difficulty falling asleep, frequent waking, and restless sleep, are frequently reported comorbidities in ASD (Liu et al, 2006; Matsuoka et al, 2014; Williams, Sears, & Allard, 2004). Recent studies report profound sleep problems in children with ASD-associated gene disruptions, CHD8 and ADNP (Bernier et al, 2014; Helsmoortel et al, 2014; Vandeweyer et al, 2014). Further exploration of sleep problems in individuals with disruptive, ASD-associated gene mutations can inform common etiological contributions to ASD and sleep by expanding symptom profiles associated with gene disruptions. Clarifying specific kinds of sleep issues accompanying ASD can better inform support of daytime behavior and functioning for children and their families. 


To provide an assay of sleep problems in individuals with ADNP, CHD8, DYRK1A, and TBR1 loss-of-function mutations. 


Participants were 14 children from the Simons Simplex Collection (SSC) sample who met strict criteria for ASD and had an ASD-associated loss-of-function gene event. Due to recurrence in the literature, the following gene events were chosen for analysis out of a larger sample of 265 children (54 female) with identified loss-of-function mutations in the SSC: CHD8 (n=8 (2 female)), ADNP (n=2 (1 female)), DYRK1A (n=2 (1 female)), and TBR1 (n=2 (1 female)). Incidences of various sleep problems were measured by parent report on a clinician-administered medical history questionnaire. Sleep-specific items were clustered into summary variables: bedtime problems, daytime sleepiness, night-time awakenings, and sleep-disordered breathing (see Table 1 for category items). For preliminary analysis, sleep summary variables were analyzed with a multivariate general linear model in relation to gene disruption type, controlling for IQ and comorbid behavior problems.


See Table 1 for incidence of sleep problems for each gene mutation group in the present sample. Preliminary analysis indicated that ADNP, CHD8, DYRK1A, and TBR1 groups differ significantly from each other in parent-reported night-time awakenings (F(1,2) = 21.05, p = 0.046). Half of each gene group endorsed frequent or prolonged awakenings at night, while the CHD8 group shows additional awakening problems in the form of sleepwalking and frequent nightmares (See Table 1, Figure 1). The incidence of night-time awakenings appears to be a significant sleep issue for individuals with one of these selected mutations (>50% endorsed) compared to the whole loss-of-function sample (<40% endorsed, see Figure 1). As additional subjects are being evaluated, continued analyses will tease apart group differences.


Deeper inspection of sleep problems in individuals with noted ASD-associated mutations to ADNP, CHD8, DYRK1A, and TBR1, while preliminary, suggests that endorsement of night-time awakenings is exacerbated in individuals with particular ASD-associated mutations. This suggests a potentially disruptive impact of these loss-of-function mutations on biological mechanisms responsible for sleep maintenance. Findings highlight night-time awakenings in this population as an area needing further study.

See more of: Genetics
See more of: Genetics