Motor Trajectories and Language Outcomes in a Genetic Model of ASD: Early Development in Fragile X with and without ASD

Background: Fragile X syndrome (FXS) is the most prevalent genetic subgroup of autism, with a comorbidity rate of 50-70%^1,2. With substantial phenotypic overlap and high ASD comorbidity, FXS offers a particularly useful ASD model for characterizing the longitudinal implications of early developmental impairments. Motor is one particular area of early impairment in FXS³ that is more significant in those with comorbid FXS and ASD^4,5. Motor has been established as an important foundation language development in children with non-syndromic ASD⁶. However, the implications of delayed motor development on language outcomes in FXS and those with FXS and ASD has yet to be examined.

Objectives: To determine whether early foundations and rate of change in fine and gross motor development predict receptive and expressive language outcomes in children with FXS-only and FXS+ASD.

Methods: Participants were from a larger prospective longitudinal study and included 43 children with FXS. According to clinical best estimate procedures 24 of the 43 participants were confirmed to have comorbid ASD (FXS+ASD). Participants were tested at regular intervals between 6 and 60 months old and groups were age-matched across assessments (p=.50; FXS M=23.86; FXS+ASD M=24.78). Study measures included the Mullen Scales of Early Learning⁷ the Vineland Adaptive Behavior Scales 2^nd Edition⁸ at each assessment. MSEL fine and gross motor raw scores were used as predictors and VABS-II receptive and expressive raw scores were used as outcome variables. We used growth models in a multilevel framework to determine level (intercept) and rate of change (slope) in fine and gross motor development over time in each group separately. Intercepts (with age centered at 9-months) and slopes were extracted and then modeled as predictors of receptive and expressive language outcomes at approximately 5-years-old in each group.

Results: Model results indicated that early gross motor (intercept) but not rate of change (slope) predicted receptive language for FXS (b=1.30; p=0.003), and FXS+ASD (b=0.88; p=0.037). This pattern was consistent between gross motor trajectories and expressive language outcomes for FXS (intercept b=5.49; p<.001); however, neither early gross motor nor rate of change predicted expressive outcomes in FXS+ASD. Early fine motor (intercepts) predicted receptive language outcomes for FXS (b=1.85; p<0.001) and FXS+ASD (b=2.54; p=0.02), whereas rate change predicted receptive outcomes only for the FXS (b=25.56; p=0.04). Early fine motor (b=6.26; p<0.001), but not rate of change, predicted expressive outcomes for FXS. Neither early fine motor, nor rate of change in fine motor predicted expressive language outcomes for FXS+ASD.

Conclusions: Study findings suggest that fine and gross motor development plays a significant role in receptive and expressive language outcomes for children with FXS. However, different patterns of influence emerged for children with FXS-only and those with FXS+ASD. Early motor foundations were a more salient predictor of both receptive and expressive outcomes for both groups. Rate of motor skill acquisition only emerged as a salient factor fine motor predicting receptive language in FXS without ASD. Decelerated motor development in FXS+ASD⁵ may account for these patterns and collective findings underscore the necessity of targeted motor intervention.