A clinical update on tuberous sclerosis complex‐associated neuropsychiatric disorders (TAND)

Tuberous sclerosis complex (TSC) is associated with a wide range of behavioral, psychiatric, intellectual, academic, neuropsychological, and psychosocial difficulties, which are often underdiagnosed and undertreated. Here, we present a clinical update on TSC‐associated neuropsychiatric disorders, abbreviated as “TAND,” to guide screening, diagnosis, and treatment in practice. The review is aimed at clinical geneticists, genetic counselors, pediatricians, and all generalists involved in the assessment and treatment of children, adolescents and adults with TSC, and related disorders. The review starts with a summary of the construct and levels of TAND, before presenting up‐to‐date information about each level of investigation. The review concludes with a synopsis of current and future TAND research.

• Publication year

  2018

• Venue

  American Journal of Medical Genetics. Part C, Seminars in Medical Genetics

• Publication date

  2018-08-16

• Fields of study

  Medicine

• Identifiers
  DOI 10.1002/ajmg.c.31637PMID 30117265PMCID PMC6209538
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Is It Feasible to Identify Natural Clusters of TSC-Associated Neuropsychiatric Disorders (TAND)?

  2018cited by this paper
• Persistence of self‐injury, aggression and property destruction in children and adults with tuberous sclerosis complex

  2018cited by this paper
• A cross-syndrome cohort comparison of sleep disturbance in children with Smith-Magenis syndrome, Angelman syndrome, autism spectrum disorder and tuberous sclerosis complex

  2018influential reference
• Beneficial Effects of Everolimus on Autism and Attention-Deficit/Hyperactivity Disorder Symptoms in a Group of Patients with Tuberous Sclerosis Complex

  2017cited by this paper
• TuberOus SClerosis registry to increase disease Awareness (TOSCA) – baseline data on 2093 patients

  2017influential reference
• mTOR inhibitor reverses autistic-like social deficit behaviours in adult rats with both Tsc2 haploinsufficiency and developmental status epilepticus

  2017cited by this paper
• Self-injury and aggression in adults with tuberous sclerosis complex: Frequency, associated person characteristics, and implications for assessment.

  2017influential reference
• Influence of seizures on early development in tuberous sclerosis complex.

  2017cited by this paper
• Everolimus for treatment of tuberous sclerosis complex‐associated neuropsychiatric disorders

  2017cited by this paper
• Early onset epileptic encephalopathy or genetically determined encephalopathy with early onset epilepsy? Lessons learned from TSC.

  2016cited by this paper
• Towards an improved understanding of TSC-Associated Neuropsychiatric Disorders (TAND)

  2016cited by this paper
• Tuberous sclerosis complex

  2016cited by this paper
• White matter disruption is associated with persistent seizures in tuberous sclerosis complex.

  2016cited by this paper
• Symptom profiles of autism spectrum disorder in tuberous sclerosis complex

  2016cited by this paper
• Adjunctive everolimus therapy for treatment-resistant focal-onset seizures associated with tuberous sclerosis (EXIST-3): a phase 3, randomised, double-blind, placebo-controlled study.

  2016cited by this paper
• Pilot validation of the tuberous sclerosis-associated neuropsychiatric disorders (TAND) checklist.

  2015cited by this paper
• Intellectual ability in tuberous sclerosis complex correlates with predicted effects of mutations on TSC1 and TSC2 proteins

  2015influential reference
• The relationship of neuroimaging findings and neuropsychiatric comorbidities in children with tuberous sclerosis complex.

  2015cited by this paper
• Intellectual abilities in tuberous sclerosis complex: risk factors and correlates from the Tuberous Sclerosis 2000 Study

  2015cited by this paper
• Neurological and neuropsychiatric aspects of tuberous sclerosis complex.

  2015influential reference
• Caring for Children With Tuberous Sclerosis Complex

  2015cited by this paper
• Advances in the treatment of tuberous sclerosis complex

  2015cited by this paper
• Tuberous sclerosis associated neuropsychiatric disorders (TAND) and the TAND Checklist.

  2015influential reference
• Self-injury and aggression in tuberous sclerosis complex: cross syndrome comparison and associated risk markers

  2014cited by this paper
• Early developmental trajectories associated with ASD in infants with tuberous sclerosis complex

  2014cited by this paper
• Intellectual development before and after the onset of infantile spasms: A controlled prospective longitudinal study in tuberous sclerosis

  2014influential reference
• Severity of manifestations in tuberous sclerosis complex in relation to genotype

  2014cited by this paper
• Autism Spectrum Disorders in Tuberous Sclerosis

  2014cited by this paper
• Assisting a child with tuberous sclerosis complex (TSC): a qualitative deep analysis of parents’ experience and caring needs

  2013cited by this paper
• Tuberous Sclerosis Complex Surveillance and Management: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference

  2013cited by this paper
• Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial.

  2013cited by this paper
• Delineating the profile of autism spectrum disorder characteristics in Cornelia de Lange and Fragile X syndromes.

  2013cited by this paper
• Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial.

  2013cited by this paper
• Fetal Brain Lesions in Tuberous Sclerosis Complex: TORC1 Activation and Inflammation

  2013cited by this paper
• Diagnostic and Statistical Manual of Mental Disorders

  2013cited by this paper
• Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 Iinternational Tuberous Sclerosis Complex Consensus Conference.

  2013cited by this paper
• Autistic-like behavior and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice

  2012cited by this paper
• Cognitive and adaptive development of patients with tuberous sclerosis complex: a retrospective, longitudinal investigation.

  2012influential reference
• Genotype and cognitive phenotype of patients with tuberous sclerosis complex

  2011cited by this paper
• Neuropsychological Attention Skills and Related Behaviours in Adults with Tuberous Sclerosis Complex

  2011cited by this paper
• Identification of risk factors for autism spectrum disorders in tuberous sclerosis complex

  2011cited by this paper
• Epilepsy and Tsc2 Haploinsufficiency Lead to Autistic-Like Social Deficit Behaviors in Rats

  2011cited by this paper
• Psychiatric Comorbidity and Treatment Response in Patients with Tuberous Sclerosis Complex

  2011cited by this paper
• Sirolimus Therapy for Angiomyolipoma in Tuberous Sclerosis and Sporadic Lymphangioleiomyomatosis: A Phase 2 Trial

  2011cited by this paper
• Long-term neurological outcome in children with early-onset epilepsy associated with tuberous sclerosis.

  2011cited by this paper
• Burden of disease and unmet needs in tuberous sclerosis complex with neurological manifestations: systematic review

  2011cited by this paper
• Neurodevelopmental, Psychiatric and Cognitive Aspects of Tuberous Sclerosis Complex

  2010influential reference
• Targeted treatments for cognitive and neurodevelopmental disorders in tuberous sclerosis complex

  2010cited by this paper
• Autism Spectrum Disorders in Tuberous Sclerosis: Pathogenetic Pathways and Implications for Treatment

  2010cited by this paper
• Targeted treatments for cognitive and neurodevelopmental disorders in tuberous sclerosis complex.

  2010cited by this paper
• Neuropsychological attention deficits in tuberous sclerosis complex (TSC)

  2009influential reference
• Attention-Deficit Hyperactivity Disorder (ADHD) and Tuberous Sclerosis Complex

  2009cited by this paper
• Development, behaviour and seizures in 300 cases of tuberous sclerosis.

  2008cited by this paper
• Characterization of Autism in Young Children With Tuberous Sclerosis Complex

  2008influential reference
• Reversal of learning deficits in a Tsc2+/− mouse model of tuberous sclerosis

  2008cited by this paper
• Cognitive impairment in tuberous sclerosis complex is a multifactorial condition

  2008cited by this paper
• Tuberous sclerosis

  2008cited by this paper
• Psychiatric comorbid conditions in a clinic population of 241 patients with tuberous sclerosis complex.

  2007influential reference
• The psychopathologies of children and adolescents with tuberous sclerosis complex (TSC)

  2007cited by this paper
• Striatal Creatine and Glutamate/Glutamine in Attention-Deficit/Hyperactivity Disorder

  2007cited by this paper
• The tuberous sclerosis complex proteins--a GRIPP on cognition and neurodevelopment.

  2007influential reference
• Psychological profile of adults with tuberous sclerosis complex.

  2007cited by this paper
• The tuberous sclerosis complex.

  2007cited by this paper
• The tuberous sclerosis complex.

  2007cited by this paper
• Neuroanatomical correlates of memory deficits in tuberous sclerosis complex.

  2007cited by this paper
• Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder.

  2007cited by this paper
• Autistic regression associated with seizure onset in an infant with tuberous sclerosis

  2006cited by this paper
• Autistic regression associated with seizure onset in an infant with tuberous sclerosis.

  2006cited by this paper
• Mutational analysis of the TSC1 and TSC2 genes in a diagnostic setting: genotype – phenotype correlations and comparison of diagnostic DNA techniques in Tuberous Sclerosis Complex

  2005cited by this paper
• Consensus clinical guidelines for the assessment of cognitive and behavioural problems in Tuberous Sclerosis

  2005cited by this paper
• Infantile spasms and intellectual outcomes in children with tuberous sclerosis complex

  2005cited by this paper
• Behavioral and Cognitive Aspects of Tuberous Sclerosis Complex

  2004cited by this paper
• Topical Review : Neuropsychiatric Problems in Tuberous Sclerosis Complex

  2004cited by this paper
• Genotype and psychological phenotype in tuberous sclerosis

  2004cited by this paper
• Follow-up of genetic linkage findings on chromosome 16p13: evidence of association of N-methyl-D aspartate glutamate receptor 2A gene polymorphism with ADHD

  2004influential reference
• Neuropsychiatric problems in tuberous sclerosis complex.

  2004cited by this paper
• Learning disability and epilepsy in an epidemiological sample of individuals with tuberous sclerosis complex

  2003influential reference
• School factors related to the social and behavioral success of children and adolescents with tuberous sclerosis: Special education placement, services, and parental involvement.

  2003cited by this paper
• The psychopathologies of attention in tuberous sclerosis

  2002cited by this paper
• Neuro-epileptic determinants of autism spectrum disorders in tuberous sclerosis complex.

  2002cited by this paper
• Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs.

  2001cited by this paper
• Cognitive deficits in normally intelligent patients with tuberous sclerosis.

  1999cited by this paper
• A Comparison of the Abilities, Health and Behaviour of 23 People with Tuberous Sclerosis at Age 5 and as Adults

  1998cited by this paper
• Molecular genetic and phenotypic analysis reveals differences between TSC1 and TSC2 associated familial and sporadic tuberous sclerosis.

  1997cited by this paper
• Sleep disorders in tuberous sclerosis: a polysomnographic study.

  1995cited by this paper
• SLEEP DISORDER AND EPILEPSY IN CHILDREN WITH TUBEROUS SCLEROSIS: A QUESTIONNAIRE‐BASED STUDY

  1994cited by this paper
• AUTISTIC BEHAVIOUR AND ATTENTION DEFICITS IN TUBEROUS SCLEROSIS: A POPULATION‐BASED STUDY

  1994cited by this paper
• Tuberous sclerosis.

  1994cited by this paper
• NEUROPSYCHOLOGICAL ASPECTS OF TUBEROUS SCLEROSIS IN RELATION TO EPILEPSY AND MRI FINDINGS

  1991cited by this paper
• Attention Deficit Hyperactivity Disorder: Fine Mapping Supports Linkage to 5p13, 6q12, 16p13, and 17p11

  year unknowninfluential reference

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• Infantile Spasms (West Syndrome): Integrating Genetic, Neurotrophic, and Hormonal Mechanisms Toward Precision Therapy

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• Developmental Trajectories of Adaptive Functioning and Behavior Problems in Children With Co-Occurring Tuberous Sclerosis Complex and Autism Spectrum Disorder, With and Without Seizures.

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• Validation of the self-report quantified Tuberous Sclerosis Complex-Associated Neuropsychiatric Disorders Checklist (TAND-SQ)

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• Neuropsychiatric disorders in Chinese pediatric tuberous sclerosis complex patients associated with drug-resistant epilepsy: A TAND checklist-based survey

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• Neurocutaneous syndromes: a multidisciplinary team approach

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• Disease Burden and Associated Factors in Chinese Patients with Tuberous Sclerosis Complex: Results of a Patient and Caregiver Survey

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• The epilepsy–autism phenotype associated with developmental and epileptic encephalopathies: New mechanism‐based therapeutic options

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• Neuropsychiatric profile in tuberous sclerosis complex patients with epilepsy

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• Diagnosis and Management of Tuberous Sclerosis Complex in a Resource-Limited Setting—A Case Report of a 14-Year-Old Female Zambian Adolescent

  2025cites this paper
• Neuropsychiatric manifestations of tuberous sclerosis in a young man in a psychiatric hospital in Botswana: a case report

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• Risk Factors for Psychiatric Disorders in Pediatric Patients with Tuberous Sclerosis Complex

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• Rare genetic interstitial lung diseases: a pictorial essay

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• Challenges in the Management of Tuberous Sclerosis-associated Neuropsychiatric Disorders

  2024cites this paper
• Prenatal mTOR Inhibitors in Tuberous Sclerosis Complex: Current Insights and Future Directions

  2024cites this paper
• Development and Pilot Validation of the DuMAND Checklist to Screen for Duchenne Muscular Dystrophy-Associated Neurobehavioral Difficulties (DuMAND)

  2024cites this paper
• Duchenne Muscular Dystrophy-Associated Neurobehavioral Difficulties: Insights from Clinical Practice

  2024cites this paper
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• De novo mutation of the TSC2 gene in patient with Tuberous Sclerosis Complex-Associated Neuropsychiatric Disorders (TAND) Phenotype: a case report

  2023cites this paper
• Is tuberous sclerosis complex-associated autism a preventable and treatable disorder?

  2023cites this paper
• Updated Genotype-Phenotype Correlations in TSC.

  2023cites this paper
• International consensus recommendations for the identification and treatment of tuberous sclerosis complex-associated neuropsychiatric disorders (TAND)

  2023cites this paper
• Updated clinical recommendations for the management of tuberous sclerosis complex associated epilepsy.

  2023cites this paper
• Astrocyte-derived complement C3 is activated in patients with tuberous sclerosis complex and mediates immune injury: an integrated bioinformatics analysis

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• Tuberous sclerosis complex presenting as afebrile encephalopathy: Diverse etiology, unitary approach

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• Prevalence of anxiety symptomatology and diagnosis in syndromic intellectual disability: a systematic review and meta-analysis.

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  2022influential citation
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• Empowering Families Through Technology: A Mobile-Health Project to Reduce the TAND Identification and Treatment Gap (TANDem)

  2022cites this paper
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  2022influential citation
• Questionnaire-based assessment of sleep disorders in an adult population of Tuberous Sclerosis Complex.

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• The association of neurodevelopmental abnormalities, congenital heart and renal defects in a tuberous sclerosis complex patient cohort

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• Postnatal Cytomegalovirus Infection May Increase the Susceptibility of Tuberous Sclerosis Complex to Autism Spectrum Disorders

  2022cites this paper
• Reading Ability in Patients With Tuberous Sclerosis Complex: Results of Chinese Character Reading and Reading Comprehension Tests

  2022cites this paper
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  2022cites this paper
• Prenatal diagnosis and intervention improve developmental outcomes and epilepsy prognosis in children with tuberous sclerosis complex

  2022cites this paper
• Sirolimus relieves seizures and neuropsychiatric symptoms via changes of microglial polarity in tuberous sclerosis complex model mice.

  2022cites this paper
• Impact of facial angiofibromas in tuberous sclerosis complex and reported efficacy of available treatments

  2022cites this paper
• The state of pediatric tuberous sclerosis complex epilepsy care: Results from a national survey

  2022cites this paper
• Satisfaction and seizure outcomes of epilepsy surgery in tuberous sclerosis: A Swedish population-based long-term follow-up study.

  2022cites this paper
• Shared mechanisms of neural circuit disruption in tuberous sclerosis across lifespan: Bridging neurodevelopmental and neurodegenerative pathology

  2022cites this paper
• Abnormal activation of yap/Taz contributes to the pathogenesis of tuberous sclerosis complex.

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• Long‐term cannabidiol treatment for seizures in patients with tuberous sclerosis complex: An open‐label extension trial

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• Involvement of mental health professionals in the treatment of tuberous sclerosis complex–associated neuropsychiatric disorders (TAND): results of a multinational European electronic survey

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  2021cites this paper
• The clinical and paraclinical manifestations of tuberous sclerosis complex in children

  2021cites this paper
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• Support for family members who are caregivers to relatives with acquired brain injury

  2021cites this paper
• Precision therapy in the genetic epilepsies of childhood

  2021cites this paper
• TSC1 and TSC2 : Tuberous Sclerosis Complex and Its Related Epilepsy Phenotype

  2021cites this paper
• Raptor downregulation rescues neuronal phenotypes in mouse models of Tuberous Sclerosis Complex

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• Tuberous sclerosis complex for the pulmonologist

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• The Complex Interplay of Cortex, Cerebellum, and Age in a Cohort of Pediatric Patients With Tuberous Sclerosis Complex.

  2021cites this paper
• Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations.

  2021cites this paper
• Beyond the Guidelines: How We Can Improve Healthcare for People With Tuberous Sclerosis Complex Around the World.

  2021cites this paper
• Patient and Caregiver Health State Utilities in Tuberous Sclerosis Complex

  2021cites this paper
• Neuropsychological and ASD phenotypes in rare genetic syndromes: A critical review of the literature

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• Multivariate data analysis identifies natural clusters of Tuberous Sclerosis Complex Associated Neuropsychiatric Disorders (TAND)

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• Behavioral Symptoms May Correlate With the Load and Spatial Location of Tubers and With Radial Migration Lines in Tuberous Sclerosis Complex

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• Adjunctive everolimus therapy for tuberous sclerosis complex‐associated refractory seizures: Results from the postextension phase of EXIST‐3

  2021cites this paper
• Epilepsy Management in Tuberous Sclerosis Complex: Existing and Evolving Therapies and Future Considerations.

  2021cites this paper
• Symptom rates and profile clustering in tuberous sclerosis complex-associated neuropsychiatric disorders (TAND)

  2021cites this paper
• Assessment of tuberous sclerosis-associated neuropsychiatric disorders using the MINI-KID tool: a pediatric cohort study

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• The TAND checklist: a useful screening tool in children with tuberous sclerosis and neurofibromatosis type 1

  2020cites this paper
• Natural clusters of tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND): new findings from the TOSCA TAND research project

  2020cites this paper
• Is autism driven by epilepsy in infants with Tuberous Sclerosis Complex?

  2020cites this paper
• West syndrome: a comprehensive review

  2020cites this paper
• Behavioral problems and family distress in tuberous sclerosis complex.

  2020cites this paper
• Event-Related Potentials in ADHD Associated With Tuberous Sclerosis Complex: A Possible Biomarker of Symptoms Severity?

  2020cites this paper
• Effects of Extended-Release Methylphenidate Treatment on Cognitive Task Performance in Children with Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder

  2020cites this paper
• Tuberous Sclerosis Complex-Associated Neuropsychiatric Disorders (TAND): New Findings on Age, Sex, and Genotype in Relation to Intellectual Phenotype

  2020cites this paper
• Tuberous Sclerosis

  2020cites this paper
• Add-on Cannabidiol Treatment for Drug-Resistant Seizures in Tuberous Sclerosis Complex

  2020cites this paper
• Quality of life in children with tuberous sclerosis complex: A pediatric cohort study

  2020cites this paper
• Neurological evaluation and management of autism spectrum disorder

  2020cites this paper
• 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.

  2019cites this paper
• Tuberous Sclerosis Complex Associated Neuropsychiatric Disorders and Parental Stress: Findings from a National, Prospective TSC Surveillance Study

  2019cites this paper
• Early Clinical Predictors of Autism Spectrum Disorder in Infants with Tuberous Sclerosis Complex: Results from the EPISTOP Study

  2019cites this paper
• A step-wise approach for establishing a multidisciplinary team for the management of tuberous sclerosis complex: a Delphi consensus report

  2019cites this paper
• Newly Diagnosed and Growing Subependymal Giant Cell Astrocytoma in Adults With Tuberous Sclerosis Complex: Results From the International TOSCA Study

  2019cites this paper
• The role of glia in epilepsy, intellectual disability, and other neurodevelopmental disorders in tuberous sclerosis complex

  2019cites this paper
• Tuberous Sclerosis (tsc2+/-) Model Eker Rats Reveals Extensive Neuronal Loss with Microglial Invasion and Vascular Remodeling Related to Brain Neoplasia

  2019cites this paper
• The Impact of Psychiatric Symptoms on Tuberous Sclerosis Complex and Utilization of Mental Health Treatment.

  2019cites this paper
• Tuberous Sclerosis Complex (TSC)

  2016cites this paper