Browsing by Author "Neuhaus, Emily"

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    Characterizing executive functioning and associated behaviors in individuals with dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) syndrome
    (Frontiers Media, 2025-01-07) 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; Pediatrics, School of Medicine
    Introduction: DYRK1A, a protein kinase located on human chromosome 21, plays a role in postembryonic neuronal development and degeneration. Alterations to DYRK1A have been consistently associated with cognitive functioning and neurodevelopmental disorders (e.g., autism, intellectual disability). However, the broader cognitive and behavioral phenotype of DYRK1A 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. Methods: Individuals with DYRK1A variants (n = 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 DYRK1A 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. Results: 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. Discussion: 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 DYRK1A syndrome and for ensuring that caregivers' concerns are addressed, and individuals receive the clinical services that best meet their needs.
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    Characterizing the autism spectrum phenotype in DYRK1A-related syndrome
    (Wiley, 2023) Kurtz-Nelson, Evangeline C.; Rea, Hannah M.; Petriceks, Aiva C.; Hudac, Caitlin M.; Wang, Tianyun; Earl, Rachel K.; Bernier, Raphael A.; Eichler, Evan E.; Neuhaus, Emily; Pediatrics, School of Medicine
    Likely gene-disrupting (LGD) variants in DYRK1A are causative of DYRK1A syndrome and associated with autism spectrum disorder (ASD) and intellectual disability (ID). While many individuals with DYRK1A syndrome are diagnosed with ASD, they may present with a unique profile of ASD traits. We present a comprehensive characterization of the ASD profile in children and young adults with LGDs in DYRK1A. Individuals with LGD variants in DYRK1A (n = 29) were compared to children who had ASD with no known genetic cause, either with low nonverbal IQ (n = 14) or average or above nonverbal IQ (n = 41). ASD was assessed using the ADOS-2, ADI-R, SRS-2, SCQ, and RBS-R. Quantitative score comparisons were conducted, as were qualitative analyses of clinicians' behavioral observations. Diagnosis of ASD was confirmed in 85% and ID was confirmed in 89% of participants with DYRK1A syndrome. Individuals with DYRK1A syndrome showed broadly similar social communication behaviors to children with idiopathic ASD and below-average nonverbal IQ, with specific challenges noted in social reciprocity and nonverbal communication. Children with DYRK1A syndrome also showed high rates of sensory-seeking behaviors. Phenotypic characterization of individuals with DYRK1A syndrome may provide additional information on mechanisms contributing to co-occurring ASD and ID and contribute to the identification of genetic predictors of specific ASD traits.
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    Shared and divergent mental health characteristics of ADNP-, CHD8- and DYRK1A-related neurodevelopmental conditions
    (Springer Nature, 2024-04-15) Neuhaus, Emily; Rea, Hannah; Jones, Elizabeth; Benavidez, Hannah; Miles, Conor; Whiting, Alana; Johansson, Margaret; Eayrs, Curtis; Kurtz‑Nelson, Evangeline C.; Earl, Rachel; Bernier, Raphael A.; Eichler, Evan E.; Pediatrics, School of Medicine
    Background: Neurodevelopmental conditions such as intellectual disability (ID) and autism spectrum disorder (ASD) can stem from a broad array of inherited and de novo genetic differences, with marked physiological and behavioral impacts. We currently know little about the psychiatric phenotypes of rare genetic variants associated with ASD, despite heightened risk of psychiatric concerns in ASD more broadly. Understanding behavioral features of these variants can identify shared versus specific phenotypes across gene groups, facilitate mechanistic models, and provide prognostic insights to inform clinical practice. In this paper, we evaluate behavioral features within three gene groups associated with ID and ASD - ADNP, CHD8, and DYRK1A - with two aims: (1) characterize phenotypes across behavioral domains of anxiety, depression, ADHD, and challenging behavior; and (2) understand whether age and early developmental milestones are associated with later mental health outcomes. Methods: Phenotypic data were obtained for youth with disruptive variants in ADNP, CHD8, or DYRK1A (N = 65, mean age = 8.7 years, 40% female) within a long-running, genetics-first study. Standardized caregiver-report measures of mental health features (anxiety, depression, attention-deficit/hyperactivity, oppositional behavior) and developmental history were extracted and analyzed for effects of gene group, age, and early developmental milestones on mental health features. Results: Patterns of mental health features varied by group, with anxiety most prominent for CHD8, oppositional features overrepresented among ADNP, and attentional and depressive features most prominent for DYRK1A. For the full sample, age was positively associated with anxiety features, such that elevations in anxiety relative to same-age and same-sex peers may worsen with increasing age. Predictive utility of early developmental milestones was limited, with evidence of early language delays predicting greater difficulties across behavioral domains only for the CHD8 group. Conclusions: Despite shared associations with autism and intellectual disability, disruptive variants in ADNP, CHD8, and DYRK1A may yield variable psychiatric phenotypes among children and adolescents. With replication in larger samples over time, efforts such as these may contribute to improved clinical care for affected children and adolescents, allow for earlier identification of emerging mental health difficulties, and promote early intervention to alleviate concerns and improve quality of life.