Longitudinal neurobehavioral profiles in children and young adults with PTEN hamartoma tumor syndrome and reliable methods for assessing neurobehavioral change

Abstract

Background: Individuals with PTEN hamartoma tumor syndrome (PHTS) demonstrate a distinct neurobehavioral profile suggesting primary disruption of frontal lobe symptoms, with more severe cognitive deficits in those with associated autism spectrum disorder (ASD) that extend to other areas of neurobehavioral function as well (e.g., adaptive behavior, sensory deficits). The current study sought to characterize longitudinal neurobehavioral profiles in individuals with PHTS who completed serial assessments (2-3 evaluations) over a 2-year time period.

Methods: Comprehensive neurobehavioral evaluations were conducted on 92 participants (age range 6-21) with PHTS and/or ASD. Spaghetti plots and linear mixed effects models were used to visualize the individual patient profiles and group trends and examine the group differences in cognitive/behavioral test scores over time. Practice-adjusted reliable change indices (RCIs) and standardized regression-based change scores (SRBs) were calculated for those measures in the battery with adequate sample sizes and test-retest reliabilities for future use in assessing neurobehavioral change in children and young adults with PHTS.

Results: Wide individual differences were observed at baseline across all measures. Encouragingly, baseline differences between patient groups persisted at the same magnitude over a 2-year time period with no differences in longitudinal neurobehavioral profiles within any one group. Test-retest reliabilities were generally high, ranging from 0.62 to 0.97, and group mean change from baseline to 12 months was small (range - 3.8 to 3.7). A Microsoft Excel calculator was created that clinicians and researchers can use to automatically calculate RCI and SRB thresholds at both 80% and 90% confidence intervals using test scores from a given child or young adult with PHTS.

Conclusions: Our results suggest that the neurobehavioral phenotypes observed in individuals with PHTS remain relatively stable over time, even in those with ASD. The RCIs and SRBs provided can be used in future research to examine patient outcomes at the individual level as well as to detect negative deviations from the expected trajectory that can be used to inform intervention strategies.

Keywords: Autism spectrum disorder; Behavior; Cognition; PTEN; PTEN hamartoma tumor syndrome; Reliable change indices; Standardized regression-based change scores.

Fig. 1

Longitudinal performance on cognitive measures. Spaghetti plots depicting cognitive performance over time on select cognitive measures. A Stanford-Binet Intelligence Scales Full Scale IQ. B Sanford-Binet Intelligence Scales Working Memory Index. C Wechsler Intelligence Scale for Children – Fifth Edition Processing Speed Index. D Expressive Vocabulary Test. Each gray line represents a single subject, while each colored line represents the group trend over time (blue: PTEN-no ASD; red: Macro-ASD; green: PTEN-ASD). Fragmented subject lines indicate the partial follow-up data