Tuberous sclerosis complex (TSC): a rare genetic condition associated with autism spectrum disorder (ASD)

Citation

Underwood, L. and Tye, C. (2016), "Tuberous sclerosis complex (TSC): a rare genetic condition associated with autism spectrum disorder (ASD)", Advances in Autism, Vol. 2 No. 2. https://doi.org/10.1108/AIA-02-2016-0005

Tuberous sclerosis complex (TSC): a rare genetic condition associated with autism spectrum disorder (ASD)

Article Type: Guest editorial From: Advances in Autism, Volume 2, Issue 2.

Welcome to this special edition of Advances in Autism on TSC. TSC is a rare genetic condition associated with a high incidence of ASD. The aim of this issue is to raise awareness of TSC among the ASD research community and demonstrate the relevance of TSC to broader neurodevelopmental and psychiatric research.

TSC is a useful model system for understanding ASD for several reasons. The prevalence of ASD is high in TSC, much higher than the general population (e.g. Bolton, 2004; Jeste et al., 2008). Despite this, phenotypic presentation is highly variable, so a moderate proportion of TSC cases do not develop ASD. This can provide valuable insight into the causal pathways leading to the emergence of ASD. Furthermore, the molecular and biological mechanisms involved in TSC are well characterised, providing a more tractable model (Huang and Manning, 2008; Orlova and Crino, 2010); Finally, a degree of homology has been demonstrated between idiopathic and syndromic ASD, suggesting similar pathways areinvolved (e.g. Bruining et al., 2014).

While not solely focused on ASD, the articles in this issue provide an overview of current TSC research, viewpoints and case studies, which taken together provide a backdrop for stimulating further research in this field in order to further our understanding of ASD and improve services for individuals and their families.

The issue opens with a review by Lisa Underwood that describes empirical research conducted to date on TSC. Despite substantial progress made in understanding the molecular and biological basis of TSC, relatively little is known about the behavioural and learning difficulties associated with TSC (including ASD), which cause significant distress to patients and their families.

The next paper is a viewpoint article by Helen Willacy, providing a parents' perspective on living with a rare genetic disorder like TSC and the challenges of dealing with multi-systemic problems. The account highlights the lack of direct assessment and treatment of neuropsychiatric disorders in TSC, which can lead to problems flying “under the radar” when accompanied by more apparent neurological issues.

The following paper by Leclezio and colleagues gives an overview of the rates and comorbidites of TSC-Associated Neuropsychiatric Disorders (TAND), and a description of the development of a TAND checklist and associated assessment guidelines for clinicians. The paper highlights the large heterogeneity in the presentation of TAND in TSC, and suggests that the future identification of “TAND clusters” (or phenotypic subtypes) may aid in targeting treatment and intervention.

The article by Tye and colleagues explores recent research and commentary on the utility of a focus on the first few years of life in TSC. Such research helps us to understand phenotypic heterogeneity and causal risk pathways in TSC, particularly in relation to ASD. The studies are reviewed in the context of altered trajectories from early in development and the proposed “homology” between ASD in its syndromic and non-syndromic form. With increasing numbers of babies with TSC being diagnosed prenatally, evidence is emerging to indicate potential cascading effects of early brain “insult” on the developing brain.

The final paper is a case study written by Clare Stuart, the General Manager of Tuberous Sclerosis Australia. The article describes the key components and approaches required to ensure success in both service provision and advice, and engagement in research. It provides key information on the challenges faced by organisations in integrating families and a large range of health professionals for a disorder that involves multiple specialties. The TSC International worldwide network also highlights the potential for international collaborations to play a key role in advancing understanding of and healthcare support for rare genetic disorders (see http://tscinternational.org).

Although written from varying perspectives, the papers in this special issue converge on common themes; the challenges faced in increasing awareness, assessment, diagnosis and ultimately targeted intervention for neuropsychiatric disorders in TSC.

We hope that in compiling this edition we have been able to highlight the value of syndromic model systems of ASD (and other neurodevelopmental disorders). Such models can be used to: provide insight into risk factors and causal pathways; identify novel pathophysiological mechanisms; target more specific treatments to individuals at risk of poor outcome; understand family and carer impact; explore transitions from childhood to adolescence to adulthood and beyond; and identify strengths and limitations of the support/services available to individuals and their families.

Findings within the TSC research field provide unique scientific utility; they lead to advances for those interested in the development, aetiology, treatment and service provision for complex disorders (including ASD) and other rare genetic syndromes. With the advent of new treatment approaches for TSC, this is a timely topic, and further findings in this and related fields are eagerly anticipated.

Lisa Underwood and Charlotte Tye

Lisa Underwood is based at School of Population Health, Faculty of Medical and Health Sciences, University of Auckland, New Zealand and Forensic and Neurodevelopmental Science, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Charlotte Tye is based at Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

References

Bolton, P. (2004), “Neuroepileptic correlates of autistic symptomatology in tuberous sclerosis”, Mental Retardation and Developmental Disabilities Research Reviews, Vol. 10 No. 2, pp. 126-31

Bruining, H., Eijkemans, M., Kas, M., Curran, S.R., Vorstman, J. and Bolton, P.F. (2014), “Behavioral signatures related to genetic disorders in autism”, Mol Autism, Vol. 5 No. 11, pp. 1-12

Huang, J. and Manning, B.D. (2008), “The TSC1-TSC2 complex: a molecular switchboard controlling cell growth”, The Biochemical journal, Vol. 412 No. 2, pp. 179-90

Jeste, S.S., Sahin, M., Bolton, P., Ploubidis, G.B. and Humphrey, A. (2008), “Characterization of autism in young children with tuberous sclerosis complex”, Journal of child neurology, Vol. 23 No. 5, pp. 520-25

Orlova, K.A. and Crino, P.B. (2010), “The tuberous sclerosis complex”, Annals of the New York Academy of Sciences, Vol. 1184 No. 1, pp. 87-105