Background: Motor dysfunction has been reported as one of the first signs of atypical development in infants at high familial risk for autism spectrum disorder (ASD) (HR infants). However, studies have shown inconsistent results regarding the nature of motor dysfunction and whether it can be predictive of later ASD diagnosis. This is likely because current standardized motor assessments may not identify subtle and specific motor impairments that precede clinically observable motor dysfunction. Quantitative measures of motor development may address these limitations by providing objective evaluation of subtle motor differences in infancy. Methods: We used Opal wearable sensors to longitudinally evaluate full day motor activity in HR infants, and develop a measure of motion complexity. We focus on complexity of motion because optimal motion complexity is crucial to normal motor development and less complex behaviors might represent repetitive motor behaviors, a core diagnostic symptom of ASD. As proof of concept, the relationship of the motion complexity measure to developmental outcomes was examined in a small set of HR infants. Results: HR infants with a later diagnosis of ASD show lower motion complexity compared to those that do not. There is a stronger correlation between motion complexity and ASD outcome compared to outcomes of cognitive ability and adaptive skills. Conclusions: Objective measures of motor development are needed to identify characteristics of atypical infant motor function that are sensitive and specific markers of later ASD risk. Motion complexity could be used to track early infant motor development and to discriminate HR infants that go on to develop ASD.

Motor impairments occur frequently in genetic syndromes highly penetrant for autism spectrum disorder (syndromic ASD) and in individuals with ASD without a genetic diagnosis (nonsyndromic ASD). In particular, abnormalities in gait in ASD have been linked to language delay, ASD severity, and likelihood of having a genetic disorder. Quantitative measures of motor function can improve our ability to evaluate motor differences in individuals with syndromic and nonsyndromic ASD with varying levels of intellectual disability and adaptive skills. To evaluate this methodology, we chose to use quantitative gait analysis to study duplication 15q syndrome (dup15q syndrome), a genetic disorder highly penetrant for motor delays, intellectual disability, and ASD. We evaluated quantitative gait variables in individuals with dup15q syndrome (n = 39) and nonsyndromic ASD (n = 21) and compared these data to a reference typically developing cohort. We found a gait pattern of slow pace, poor postural control, and large gait variability in dup15q syndrome. Our findings improve characterization of motor function in dup15q syndrome and nonsyndromic ASD. Quantitative gait analysis can be used as a translational method and can improve our identification of clinical endpoints to be used in treatment trials for these syndromes. Autism Res 2020, 13: 1102‐1110. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.Lay SummaryMotor impairments, particularly abnormalities in walking, occur frequently in genetic syndromes highly penetrant for autism spectrum disorder (syndromic ASD). Here, using quantitative gait analysis, we find that individuals with duplication 15q syndrome have an atypical gait pattern that differentiates them from typically developing and nonsyndromic ASD individuals. Our findings improve motor characterization in dup15q syndrome and nonsyndromic ASD.

Despite the sparse visual information and paucity of self-identifying cues provided by point-light stimuli, as well as a dearth of experience in seeing our own-body movements, people can identify themselves solely based on the kinematics of body movements. The present study found converging evidence of this remarkable ability using a broad range of actions with whole-body movements. In addition, we found that individuals with a high degree of autistic traits showed worse performance in identifying own-body movements, particularly for simple actions. A Bayesian analysis showed that action complexity modulates the relationship between autistic traits and self-recognition performance. These findings reveal the impact of autistic traits on the ability to represent and recognize own-body movements.

Spinocerebellar ataxia type 21 (SCA21/ATX-TMEM240) is a rare form of cerebellar ataxia that commonly presents with motor, cognitive, and behavioral impairments. Although these features have been identified as part of the clinical manifestations of SCA21, the neurodevelopmental disorders associated with SCA21 have not been well studied or described. Here we present extensive phenotypic data for 3 subjects from an SCA21 family in the United States. Genetic testing demonstrated the c.196 G>A (p.Gly66Arg) variant to be a second recurrent mutation associated with the disorder. Standardized developmental assessment revealed significant deficits in cognition, adaptive function, motor skills, and social communication with 2 of the subjects having diagnoses of autism spectrum disorder, which has never been described in SCA21. Quantitative gait analysis showed markedly abnormal spatiotemporal gait variables indicative of poor gait control and cerebellar as well as noncerebellar dysfunction. Clinical evaluation also highlighted a striking variability in clinical symptoms, with greater ataxia correlating with greater severity of neurodevelopmental disorder diagnoses. Notably, neurodevelopmental outcomes have improved with intervention over time. Taken together, this case series identifies that the manifestation of neurodevelopmental disorders is a key feature of SCA21 and may precede the presence of motor abnormalities. Furthermore, the coexistence of ataxia and neurodevelopmental disorders in these subjects suggests a role for spinocerebellar pathways in both outcomes. The findings in this study highlight the importance of evaluation of neurodevelopmental concerns in the context of progressive motor abnormalities and the need for timely intervention to ultimately improve quality of life for individuals with SCA21.