Fragile X syndrome (FXS) is the most common known genetic cause of autism spectrum disorder (ASD). Although 50-75% of children with FXS meet ASD criteria, no studies have compared ASD symptoms in infants with FXS versus other high risk groups, such as siblings of children with ASD (ASIBs). Using the Autism Observation Scale for Infants, our findings indicate that 53% of 12-month infants with FXS fall in the "at risk" category compared to 17 and 6% for age-matched ASIBs and controls, respectively. Elevated atypical motor behaviors were associated with elevated risk for FXS. Cross-syndrome comparisons are essential to understanding the heterogeneity of ASD and identifying candidate markers that will facilitate differential diagnosis of ASD in genetic disorders such as FXS.