Psychiatric Characteristics Across Individuals With PTEN Mutations

Abstract

Germline heterozygous PTEN mutations have been associated with high prevalence of autism spectrum disorder (ASD) and elevated rates and severity of broadly defined behavioral problems. However, limited progress has been made toward understanding whether PTEN mutation is associated with specific psychiatric co-morbidity profiles when compared to idiopathic ASD. The current study aimed to utilize a cross-measure approach to compare concurrent psychiatric characteristics across children and adolescents with PTEN mutation with (PTEN-ASD; n = 38) and without ASD (PTEN-No ASD; n = 23), and ASD with macrocephaly but no PTEN mutation (macro-ASD; n = 25) using the Child Behavior Checklist (CBCL) and the Aberrant Behavior Checklist (ABC). There were significant group effects for the CBCL Internalizing and Externalizing broad symptom score, the majority of specific CBCL syndrome scores, and all ABC subscale scores. Post-hoc comparisons revealed greater behavioral symptoms in the ASD groups (PTEN-ASD and macro-ASD) compared to the PTEN-no ASD group on nearly all subtest scores examined. There were no statistically significant differences between the PTEN-ASD and macro-ASD groups; however, there was a trend for the macro-ASD group showing higher levels of aggressive behaviors. Our findings provide evidence of specific behavior profiles across PTEN-No ASD, PTEN-ASD, and macro-ASD groups and highlight the importance of early identification of behavioral vulnerabilities in individuals with PTEN mutations in order to provide access to appropriate evidence-based interventions.

Development of informant‐report neurobehavioral survey scales for PTEN hamartoma tumor syndrome and related neurodevelopmental genetic syndromes

“…The pronounced variability and complexity in the profiles of NDD and NPD symptoms, cognitive processing, and adaptive abilities seen in individuals with PHTS (Balci et al, 2018; Busch et al, 2013, 2019; Frazier et al, 2015; Frazier et al, 2021; Hansen‐Kiss et al, 2017; Hobert et al, 2014; Steele et al, 2021; Uljarevic et al, 2021a, 2021b) and other NDGS (Agarwal et al, 2019; Arnett et al, 2018; Berryer et al, 2013; Jimenez‐Gomez et al, 2019; Mulder et al, 2020; Parker et al, 2015; Rai et al, 2018) present a significant assessment challenge. Although a range of currently available and widely‐used instruments have been developed to capture discrete clinical presentations in PHTS and other NGDS, including ASD, ADHD, internalizing and externalizing symptoms, these tools tend to evaluate either a single broad construct or only a subset of relevant symptoms or behaviors.…”

“…Social communication/interaction, daily living skills, executive functioning, and quality of life levels tended to fall 1-2SD below the control mean, and motor skills fell more than 3SD below the control mean. The pronounced variability and complexity in the profiles of NDD and NPD symptoms, cognitive processing, and adaptive abilities seen in individuals with PHTS (Balci et al, 2018;Busch et al, 2013Busch et al, , 2019Frazier et al, 2015;Frazier et al, 2021;Hansen-Kiss et al, 2017;Hobert et al, 2014;Steele et al, 2021;Uljarevic et al, 2021aUljarevic et al, , 2021b and other NDGS (Agarwal et al, 2019;Arnett et al, 2018;Berryer et al, 2013;Jimenez-Gomez et al, 2019;Mulder et al, 2020;Parker et al, 2015;Rai et al, 2018) present a significant assessment challenge. Although a range of currently available and widely-used instruments have been developed to capture discrete clinical presentations T A B L E 2 Factor analysis results by survey scale.…”

“…Levels of RRB and other clinical symptoms, including anxiety, have also been linked to difficulties in executive functioning in PHTS (Uljarevic et al, 2021a), emphasizing the need for simultaneous assessment of multiple domains. Further supporting the need for broad neurobehavioral evaluation, a recent study using a cross-measure approach has demonstrated high prevalence as well as significant individual differences in concurrent psychiatric symptoms among children and adolescents with PHTS (Steele et al, 2021), with a significant negative impact on affected individuals and their families (Macken et al, 2019).…”

Systematic Bibliometric and Visualized Analysis of Research Hotspots and Trends on Autism Spectrum Disorder Neuroimaging

“…Several studies have also demonstrated that ASD has atypical features of FA and FC when performing language judgment, facial difference recognition, and memory tasks [51][52][53]. Neuroscience research on early identification of ASD or people at high risk for ASD has been emphasized [54,55]. Earlier studies have established that the atypical development of ASD is related to the abnormal wholebrain connection, which may be congenital [56].…”

Development of webcam‐collected and artificial‐intelligence‐derived social and cognitive performance measures for neurodevelopmental genetic syndromes

“…This work is crucial to developing patient support guidelines and ensuring that patients with NDGS receive appropriate supports that maximize their development. For example, in individuals with PTEN hamartoma tumor syndrome (PHTS) resulting from germline heterozygous mutations in PTEN , a spectrum of frontal‐systems deficits has been identified from no impairment to very severe impairment associated with intellectual disability (ID) and autism spectrum disorder (ASD) (Busch et al, 2019; Ciaccio et al, 2018; Frazier et al, 2015; Steele et al, 2021). This pattern has been found to be stable over a period of 2 years (Busch et al, 2023), even in young children, and the specific profile of frontal systems impairment can be used to inform clinical and educational care (Frazier, 2019).…”