New insights into the pathogenesis and prevention of tuberous sclerosis-associated neuropsychiatric disorders (TAND)

Gipson, Tanjala; Johnston, Michael V.

doi:10.12688/f1000research.11110.1

Cited by 13 publications

(10 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…mTOR is a key pathway involved in protein synthesis, cell proliferation, and cell growth (Sundberg and Sahin, 2015). In addition to epilepsy and complications to tuber formation throughout the body, approximately 50% of TSC patients meet the criteria for diagnosis of ASD, with a substantial portion of others suffering more subtle neuropsychiatric disturbances (Sundberg and Sahin, 2015; Gipson and Johnston, 2017). Though a previous study linked cerebellar tuber formation to the development of ASD (Weber et al, 2000), more recent efforts have been made to investigate how Purkinje cell function is specifically disrupted through targeted knock-out of TSC1 in Purkinje cells (Tsai et al, 2012; Stoodley et al, 2018).…”

Section: Mouse Models Of Cerebellar Cognitive Disordersmentioning

confidence: 99%

Functional Outcomes of Cerebellar Malformations

Gill

Sillitoe

2019

Front. Cell. Neurosci.

View full text Add to dashboard Cite

The cerebellum is well-established as a primary center for controlling sensorimotor functions. However, recent experiments have demonstrated additional roles for the cerebellum in higher-order cognitive functions such as language, emotion, reward, social behavior, and working memory. Based on the diversity of behaviors that it can influence, it is therefore not surprising that cerebellar dysfunction is linked to motor diseases such as ataxia, dystonia, tremor, and Parkinson’s disease as well to non-motor disorders including autism spectrum disorders (ASD), schizophrenia, depression, and anxiety. Regardless of the condition, there is a growing consensus that developmental disturbances of the cerebellum may be a central culprit in triggering a number of distinct pathophysiological processes. Here, we consider how cerebellar malformations and neuronal circuit wiring impact brain function and behavior during development. We use the cerebellum as a model to discuss the expanding view that local integrated brain circuits function within the context of distributed global networks to communicate the computations that drive complex behavior. We highlight growing concerns that neurological and neuropsychiatric diseases with severe behavioral outcomes originate from developmental insults to the cerebellum.

show abstract

Section: Mouse Models Of Cerebellar Cognitive Disordersmentioning

confidence: 99%

Functional Outcomes of Cerebellar Malformations

Gill

Sillitoe

2019

Front. Cell. Neurosci.

View full text Add to dashboard Cite

show abstract

“…28 Moreover, there has been growing interest in the treatment of TAND, through such modalities as mTOR inhibitors despite limited clinical evidence to directly support their use. 12,[30][31][32][33] Education of all health care providers is therefore imperative to ensure that TAND symptoms are better recognized and treated. Future studies should address ways to improve the recognition, knowledge, and treatment of TAND among health care providers as well as patients and their families.…”

Section: Discussionmentioning

confidence: 99%

A Review of Investigations for Patients With Tuberous Sclerosis Complex Who Were Referred to the Tuberous Sclerosis Clinic at The Hospital for Sick Children: Identifying Gaps in Surveillance

Alsowat

Zak

McCoy

et al. 2020

Pediatric Neurology

View full text Add to dashboard Cite

“…Tuberous sclerosis, for example, is a multisystem disorder resulting from mutations in either the TSC1 or TSC2 genes, leading to abnormal signalling in the mammalian target of rapamycin (mTOR) pathway. The condition is commonly associated with autism in up to 61% of patients, with the presence of renal angiomyolipomata, cystic kidney disease and hypertension in 80% [21]. Phase 3 everolimus trials, EXIST-1 and EXIST-2, demonstrate that everolimus may reduce angiomyolipoma lesion volume and preserve kidney function in most patients [22].…”

Section: Genetic Syndromesmentioning

confidence: 99%

Autism spectrum disorder and kidney disease

Clothier

Absoud

2020

Pediatr Nephrol

View full text Add to dashboard Cite

Neurodevelopmental impairments have been recognised as a major association of paediatric kidney disease and bladder dysfunction, presenting challenges to clinicians and families to provide reasonable adjustments in order to allow access to investigations and treatments. Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterised by impairments in social interaction/communication and repetitive sensory-motor behaviours. Mental health, learning and physical co-morbidities are common. There is emerging evidence that ASD and kidney disease have some overlaps with genetic copy number variants and environmental factors contributing to shared pathogenesis. Prevalence rates of ASD in kidney disease are currently not known. A high index of suspicion of underlying ASD is required when a young person presents with communication difficulties, anxiety or behaviour that challenges, which should then trigger referral for a neurodevelopmental and behavioural assessment. We discuss practical approaches for providing care, which include understanding methods of communication and sensory, behavioural and environmental adaptations.

show abstract

New insights into the pathogenesis and prevention of tuberous sclerosis-associated neuropsychiatric disorders (TAND)

Cited by 13 publications

References 65 publications

Functional Outcomes of Cerebellar Malformations

Functional Outcomes of Cerebellar Malformations

A Review of Investigations for Patients With Tuberous Sclerosis Complex Who Were Referred to the Tuberous Sclerosis Clinic at The Hospital for Sick Children: Identifying Gaps in Surveillance

Autism spectrum disorder and kidney disease

Contact Info

Product

Resources

About