TSC
Tuberous Sclerosis Complex, abbreviated to ‘TSC’, is a rare genetic disorder. It is caused by mutations in the genes TSC1 or TSC2 that produces the proteins hamartin and tuberin respectively. TSC affects approximately 1 in 6000 individuals involving all racial and ethnic groups. That means that there are about 1-2 million people around the globe who have the disorder.
Mutations in TSC2 are more common and are usually associated with more severe manifestations than those in TSC1. People with TSC develop benign tumors (known as hamartomas) in multiple organ systems including the skin, the brain, the heart, the kidneys, the eyes and the lungs, but these manifestations can vary significantly between different people with the disorder. Some people can therefore have very few physical manifestations, while others have many or very severe physical manifestations.
What is TSC?
[tscalliance.org]
What is TSC?
[tuberous-sclerosis.org]
What is TSC?
[tscinternational.org]
TAND
Apart from the physical manifestations of TSC, most individuals with Tuberous Sclerosis Complex (about 90%) are affected by a broad range of behavioural, psychiatric, intellectual, academic, neuropsychological and psychosocial difficulties. Examples include autism, ADHD, intellectual disability, anxiety and depressive disorders, and difficulties in scholastic skills. These problems often cause the greatest burden to individuals with TSC and their families. Unfortunately, they are often not identified or treated.
The Neuropsychiatry Panel of the International TSC Consensus Conference in 2012 realised that there was a big gap in the identification and treatment of these difficulties. In order to reduce this ‘identification gap’ we created the term ‘TAND’, which stands for TSC-Associated Neuropsychiatric Disorders. The inspiration for the name came from the HIV community. In HIV clinical services doctors and nurses had become very good at identifying and treating the physical features of HIV. But, many people with HIV also had learning and mental health problems. The HIV community introduced the term HAND (HIV-Associated Neurocognitive Disorders) as a strategy to increase awareness and action around HAND. We therefore decided to use a similar strategy for TSC. To generate a ‘shared language’ that might support international communication and to guide future research, we described six distinct levels of TAND, as shown in the umbrella figure below.
TAND levels
The umbrella figure below highlights six levels of TAND. These levels highlight that TAND can impact individuals on an individual behaviour level, a diagnostic level, intellectual level, scholastic level, neuropsychological level, and psychosocial level. The table below summarises how these different levels might be evaluated in an individual with TAND.
Behavioural level
Behavioural problems in themselves do not constitute a psychiatric disorder, given that different elements need to be taken into account to determine whether or not behaviour is appropriate and what the reason is for a person’s behaviour. Temper tantrums in a two-year-old, for example, are appropriate to the developmental level of the child, and usually do not require additional supervision. The same behavior in a 15-year-old does request additional evaluation to understand what the reasons and triggers are. The behavioural level therefore often represents a reason for referral for additional evaluation by a doctor or other specialists.
TSC-Associated Neuropsychiatric Disorders (TAND): Findings from the TOSCA Natural History Study
[ojrd.biomedcentral.com]
Psychiatric level
At this level, the behaviour is evaluated in the context of a person’s general development and biological, psychological and social profile. When someone exhibits pronounced behavioural problems that persist over time and are a major source of stress or disability, a psychiatric disorder may be diagnosed, as defined in DSM-5 or ICD-11. The most common psychiatric disorders associated with TSC are autism (40 – 50%), ADHD (30 – 50%), and depressive and anxiety disorders (30 – 60%). Psychosis does not appear to be more common than in the general population and most psychotic symptoms in TSC are associated with seizures, especially those originating in the temporal lobe. Diagnosis of a psychiatric disorder is crucial as a stepping stone to appropriate parent/caregiver education and training, individual or other interventions, educational interventions or targeted support for employment.
Intellectual level
About half of people with TSC have an intellectual disability, defined as an IQ score <70, ranging from mild to severe. The IQ profile is often discordant, with strongly fluctuating strengths and weaknesses, even in people with a normal IQ. The evaluation of intellectual capacities is essential for interpreting behavioral problems, but also for the search for optimal learning path counseling at school or work.
Academic level
The majority of school-aged children with TSC (even if they have normal intellectual abilities) have scholastic difficulties requiring further assessment and guidance. These children are often incorrectly labeled as “stubborn” or “lazy” and therefore may miss out on appropriate educational support.
Neuropsychological level
Neuropsychological assessments are used to map specific strengths and weaknesses of the various brain functions required for learning, thinking and behavioural regulation. On the one hand, these neuropsychological functions show a clear correlation with behavioural problems, psychiatric disorders, intellectual abilities and school functioning.
On the other hand, people with TSC can also show very specific neuropsychological deficits (score <Pc 5) such as, for example, difficulties in performing two tasks at the same time or problems with organisation and planning, which can significantly interfere with day-to-day functioning.
Psychosocial level
At this level, important determinants of quality of life are mapped, such as selfimage, family functioning, parental stress, and relationship problems. This largely reflects the resilience or burden of care in a family. Although the psychosocial problems associated with TSC are often particularly serious, people with TSC and their families are rarely questioned by health care providers about these nonmedical aspects of the disease.
Quality of Life in Children with Tuberous Sclerosis Complex: A Pediatric Cohort Study
[onlinelibrary.wiley.com]
Burden of Illness and Quality of Life in Tuberous Sclerosis Complex: Findings from the TOSCA Study
[pubmed.ncbi.nlm.nih.gov]
How to evaluate the different levels of TAND
Behavioural level
All observed behaviours. Evaluation through direct observation by parents, family, teachers or caregivers, or using a range of questionnaires.
Psychiatric level
Defined by diagnostic classification systems such as DSM-5 or ICD-11. At this level, the clinician with training in mental health disorders determines whether behaviours observed at the behavioural level meet the criteria for specific psychiatric disorders.
Intellectual level
General level of intellectual development as measured by standardized IQ (intelligence quotient) measures, and by evaluation of adaptive behaviours in daily life.
Academic level
Refers to specific learning disorders such as defined by DSM-5 or ICD-11, such as reading, writing, spelling or mathematics disorders.
Neuropsychological level
Brain skills such as language, executive skills, memory and visuo-spatial skills, evaluated using standardized neuropsychological instruments.
Psychosocial level
The psychological and social impact of TSC on the individual with TSC, the family and their community. Psychosocial functioning can be measured by some specific rating scales and through asking people about this.
Notes: ADHD: Attention Deficit and Hyperactivity Disorder; DSM-5: Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (American Psychiatric Association, 2013); ICD-11: International Classification of Diseases and Related Health Problems, 11th Edition (WHO, 2018).
Behavioural level
All observed behaviours. Evaluation through direct observation by parents, family,teachers or caregivers, or using a range of questionnaires.
Psychiatric level
Defined by diagnostic classification systems such as DSM-5 or ICD-11. At this level, the clinician with training in mental health disorders determines whetherbehaviours observed at the behavioural level meet the criteria for specific psychiatric disorders.
Intellectual level
General level of intellectual development as measured by standardized IQ(intelligence quotient) measures, and by evaluation of adaptive behaviours in dailylife.
Academic level
Refers to specific learning disorders such as defined by DSM-5 or ICD-11, such as reading, writing, spelling or mathematics disorders.
Neuropsychological level
Brain skills such as language, executive skills, memory and visuo-spatial skills,evaluated using standardized neuropsychological instruments.
Psychosocial level
The psychological and social impact of TSC on the individual with TSC, the family and their community. Psychosocial functioning can be measured by some specific rating scales and through asking people about this.
Notes: ADHD: Attention Deficit and Hyperactivity Disorder; DSM-5: Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (American Psychiatric Association, 2013); ICD-11: International Classification of Diseases and Related Health Problems, 11th Edition (WHO, 2018).
TAND clusters
Not only do TAND impact an individual across these six levels, research has shown that they can also cluster together in seven natural TAND clusters. These natural TAND clusters are summarised in the table below.
Autism-like cluster
Absence or delayed onset of language, repeats words or phrases, poor eye contact, difficulty in peer relationships, repetitive behaviours, rigid or inflexible behaviour, sensory sensitivities.
Dysregulated behaviour cluster
Aggressive outbursts, temper tantrums, self-injury.
Eat/Sleep cluster
Difficulties with eating and/or drinking, difficulties with sleeping.
Mood/Anxiety cluster
Anxiety, depressed mood, extreme shyness, and mood swings.
Neuropsychological cluster
Difficulties in motor skills, language skills, attention or concentration, dual/multi-tasking, memory, visuo-spatial tasks, executive skills, orientation, processing speed.
Overactive/Impulsive cluster
Overactivity/ hyperactivity, restlessness or fidgetiness, and impulsivity.
Scholastic cluster
Difficulties in reading, writing, spelling and mathematics.
In light of the enormous variability of TAND, these natural TAND clusters can be helpful in suggesting next steps for evaluation or intervention for TAND. The consortium also identified an eighth wraparound psychosocial cluster focused on the psychosocial burden of TAND for individuals with TSC and their caregivers. This burden can present as difficulties with self-esteem, stress in the family and family relationships, difficulty connecting with others in the community, and difficulty in career progress.
Consensus recommendations for TAND
The consortium developed international consensus recommendations for TAND according to these natural clusters, as well as a wraparound psychosocial cluster for both individuals with TSC and their caregivers.
