Tuberous Sclerosis Complex Associated with Autism Spectrum Features and Bumetanide as a Pharmacological Indication: A Case Report

Abstract Tuberous sclerosis complex (TSC) is a rare genetic disorder characterized by benign tumors throughout the body; it is generally diagnosed early in life and has a high prevalence of autism spectrum disorder (ASD), making it uniquely valuable in studying the early development of autism, before neuropsychiatric symptoms become apparent. One well-documented deficit in ASD is an impairment in face processing. In this work, we assessed whether anatomical connectivity patterns of the fusiform gyrus, a central structure in face processing, capture the risk of developing autism early in life. We longitudinally imaged TSC patients at 1, 2, and 3 years of age with diffusion compartment imaging. We evaluated whether the anatomical connectivity fingerprint of the fusiform gyrus was associated with the risk of developing autism measured by the Autism Observation Scale for Infants (AOSI). Our findings suggest that the fusiform gyrus connectivity captures the risk of developing autism as early as 1 year of age and provides evidence that abnormal fusiform gyrus connectivity increases with age. Moreover, the identified connections that best capture the risk of developing autism involved the fusiform gyrus and limbic and paralimbic regions that were consistent with the ASD phenotype, involving an increased number of left-lateralized structures with increasing age.

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Tuberous sclerosis complex with oral manifestations: A case report and literature review

Medicina Oral Patología Oral y Cirugia Bucal ◽

10.4317/medoral.16.e478 ◽

2011 ◽

pp. e478-e481 ◽

Cited By ~ 8

Author(s):

K. Harutunian ◽

R. Figueiredo ◽

C. Gay-Escoda

Keyword(s):

Case Report ◽

Literature Review ◽

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Oral Manifestations

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

Journal of Neurodevelopmental Disorders ◽

10.1186/s11689-019-9293-x ◽

2019 ◽

Vol 11 (1) ◽

Cited By ~ 10

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.

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