Detection of Autism in Infants with Fragile X Syndrome

Background: Fragile X syndrome (FXS) is the leading known heritable cause of intellectual disability affecting approximately 1: 3,600 individuals.  Autism is one of the most prevalent and severe behavioral abnormalities associated with FXS with up to 90% of males with FXS exhibiting one or more features of autism, and 25% to 50% meeting DSM IV based diagnostic criteria for autism.  In the field of idiopathic autism (non-FXS), an increased focus on the emergence of autistic behavior in the first year of life has revealed a number of behaviors that appear to be early indicators of autism.  These behaviors include atypicalities such as prolonged latency to disengage visual attention and a pattern of early temperament characterized by passivity and decreased activity at 6 months followed by intense distress reactions and decreased positive affect in the second year of life (Zwaigenbaum et al., 2005).  Given the high co-morbidity of autism in FXS and its debilitating effects, we are investigating early emerging behavioral indicators of autism and possible underlying physiological markers in infants with FXS.  In preliminary work, we found that 12-month-old infants with FXS (n=11) displayed longer look durations and longer latencies to disengage visual attention than typically developing controls (n=9).  There was a moderate relationship between increased look duration to both increased severity of autistic behavior and elevated heart rate during decelerative phases (reflected cognitive processing) in the infants with FXS.  The current work extends these findings.

Objectives: To identify early emerging behavioral features and potential underlying physiological mechanisms associated with the emergence of autism in FXS.

Methods: Using a prospective longitudinal design integrating behavioral and physiological methods, we will examine the relationship among maternal ratings and experimental laboratory based measures of temperament and heart activity to autistic behavior in a cohort of 12 infants with FXS assessed at 9, 12, 18 and 36 months of age.  Additionally, we will conduct a cross-sectional analysis with a sample of 23 infants with FXS (aged 9 to 36 months). Our analyses are only partially complete at this time; however, all the data are collected, entered, and edited.  We anticipate running the full model analyses in the next month.

Results: Analyses are limited to descriptive data at this time.  These preliminary data suggest that the temperament profile of infants with FXS does increase in intensity over time with elevations in anger and lessened soothability and decreased attention observed across time on maternal ratings.  Heart activity reflects elevated arousal and decreased variability as reported for older-aged children with FXS.

Conclusions: Infants with FXS are at very high risk for autism.  Thus, understanding the early behavioral indicators of autism and possible underlying physiological mechanisms in the first years of life is critical to guiding diagnostic and treatment efforts in this high-risk population.