scholarly journals Early developmental pathways to autism spectrum disorder in tuberous sclerosis complex

2016 ◽  
Vol 2 (2) ◽  
pp. 84-93 ◽  
Author(s):  
Charlotte Tye ◽  
Kandice Varcin ◽  
Patrick Bolton ◽  
Shafali Spurling Jeste
Keyword(s):  
Autism Spectrum Disorder ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Developmental Trajectories ◽  
Genetic Disorder ◽  
Familial Risk ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Content Type ◽  
Cascading Effects

Purpose – Tuberous sclerosis complex (TSC) is a genetic disorder with a high prevalence of autism spectrum disorder (ASD), yet no single genetic, neurological or neurophysiological risk marker is necessary or sufficient to increase risk for ASD. This paper aims to discuss the utility of adopting a developmental perspective. Design/methodology/approach – The increasing number of TSC infants presenting with abnormalities prenatally provides a unique opportunity to study risk pathways to ASD from birth. Here, the authors review findings to date that support the investigation of infants with TSC to further our understanding of typical and atypical development. Findings – Evidence has accumulated from studies of infants at familial risk for ASD (“baby siblings”) to suggest that early markers of ASD are present in the first year of life. The early waves of prospective studies of infants with TSC indicate dynamic changes in developmental trajectories to ASD and are likely to provide insight into cascading effects of brain “insult” early in development. Emerging evidence of phenotypic and biological homology between syndromic and idiopathic cases of ASD supports the notion of a convergence of risk factors on a final common pathway in ASD. Originality/value – The delineation of brain-based biomarkers of risk, prediction and treatment response in TSC will be critical in aiding the development of targeted intervention and prevention strategies for those infants at high risk of poorer developmental outcomes.

scholarly journals Early white matter development is abnormal in tuberous sclerosis complex patients who develop autism spectrum disorder

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna K. Prohl ◽  
◽  
Benoit Scherrer ◽  
Xavier Tomas-Fernandez ◽  
Peter E. Davis ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
White Matter ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Neural Circuits ◽  
Diffusion Tensor ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Fiber Bundles ◽  
The Brain

Abstract Background Autism spectrum disorder (ASD) is prevalent in tuberous sclerosis complex (TSC), occurring in approximately 50% of patients, and is hypothesized to be caused by disruption of neural circuits early in life. Tubers, or benign hamartomas distributed stochastically throughout the brain, are the most conspicuous of TSC neuropathology, but have not been consistently associated with ASD. Widespread neuropathology of the white matter, including deficits in myelination, neuronal migration, and axon formation, exist and may underlie ASD in TSC. We sought to identify the neural circuits associated with ASD in TSC by identifying white matter microstructural deficits in a prospectively recruited, longitudinally studied cohort of TSC infants. Methods TSC infants were recruited within their first year of life and longitudinally imaged at time of recruitment, 12 months of age, and at 24 months of age. Autism was diagnosed at 24 months of age with the ADOS-2. There were 108 subjects (62 TSC-ASD, 55% male; 46 TSC+ASD, 52% male) with at least one MRI and a 24-month ADOS, for a total of 187 MRI scans analyzed (109 TSC-ASD; 78 TSC+ASD). Diffusion tensor imaging properties of multiple white matter fiber bundles were sampled using a region of interest approach. Linear mixed effects modeling was performed to test the hypothesis that infants who develop ASD exhibit poor white matter microstructural integrity over the first 2 years of life compared to those who do not develop ASD. Results Subjects with TSC and ASD exhibited reduced fractional anisotropy in 9 of 17 white matter regions, sampled from the arcuate fasciculus, cingulum, corpus callosum, anterior limbs of the internal capsule, and the sagittal stratum, over the first 2 years of life compared to TSC subjects without ASD. Mean diffusivity trajectories did not differ between groups. Conclusions Underconnectivity across multiple white matter fiber bundles develops over the first 2 years of life in subjects with TSC and ASD. Future studies examining brain-behavior relationships are needed to determine how variation in the brain structure is associated with ASD symptoms.

scholarly journals Early patterns of functional brain development associated with autism spectrum disorder in tuberous sclerosis complex

2019 ◽  
Vol 12 (12) ◽  
pp. 1758-1773 ◽  
Author(s):  
Abigail Dickinson ◽  
Kandice J. Varcin ◽  
Mustafa Sahin ◽  
Charles A. Nelson ◽  
Shafali S. Jeste
Keyword(s):  
Autism Spectrum Disorder ◽  
Brain Development ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Functional Brain

scholarly journals Actigraph-Measured Movement Correlates of Attention-Deficit/Hyperactivity Disorder (ADHD) Symptoms in Young People with Tuberous Sclerosis Complex (TSC) with and without Intellectual Disability and Autism Spectrum Disorder (ASD)

2020 ◽  
Vol 10 (8) ◽  
pp. 491
Author(s):  
Tom Earnest ◽  
Elizabeth Shephard ◽  
Charlotte Tye ◽  
Fiona McEwen ◽  
Emma Woodhouse ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Attention Deficit Hyperactivity Disorder ◽  
Tuberous Sclerosis ◽  
Attention Deficit ◽  
Genetic Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Adhd Symptoms ◽  
Negatively Associated ◽  
Hyperactivity Disorder

Actigraphy, an objective measure of motor activity, reliably indexes increased movement levels in attention-deficit/hyperactivity disorder (ADHD) and may be useful for diagnosis and treatment-monitoring. However, actigraphy has not been examined in complex neurodevelopmental conditions. This study used actigraphy to objectively measure movement levels in individuals with a complex neurodevelopmental genetic disorder, tuberous sclerosis (TSC). Thirty participants with TSC (11–21 years, 20 females, IQ = 35–108) underwent brief (approximately 1 h) daytime actigraph assessment during two settings: movie viewing and cognitive testing. Multiple linear regressions were used to test associations between movement measurements and parent-rated ADHD symptoms. Correlations were used to examine associations between actigraph measures and parent-rated ADHD symptoms and other characteristics of TSC (symptoms of autism spectrum disorder (ASD), intellectual ability (IQ), epilepsy severity, cortical tuber count). Higher movement levels during movies were associated with higher parent-rated ADHD symptoms. Higher ADHD symptoms and actigraph-measured movement levels during movies were positively associated with ASD symptoms and negatively associated with IQ. Inter-individual variability of movement during movies was not associated with parent-rated hyperactivity or IQ but was negatively associated with ASD symptoms. There were no associations with tuber count or epilepsy. Our findings suggest that actigraph-measured movement provides a useful correlate of ADHD in TSC.

scholarly journals Language predictors of autism spectrum disorder in young children with tuberous sclerosis complex

2020 ◽  
Vol 103 ◽  
pp. 106844 ◽  
Author(s):  
Alexandra Schoenberger ◽  
Jamie K. Capal ◽  
Annie Ondracek ◽  
Paul S. Horn ◽  
Donna Murray ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Young Children ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Autism Spectrum ◽  
Spectrum Disorder
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