Tuberous sclerosis complex (TSC) is a genetic condition characterised by development of benign tumours (also known as hamartomas) that can affect multiple organs.^1,2 These tumours are non-cancerous, however they can grow larger and damage the organs, leading to a range of symptoms.³ Organs such as the skin, brain, kidneys, heart, eyes and lungs are frequently affected. The number, size, and location of these tumours can vary between individuals.⁴ TSC is caused by genetic changes in the TSC1 or TSC2 genes, leading to uncontrollable cell growth and formation of the tumours.

Synonyms: Bourneville syndrome, Bourneville Pringle syndrome, tuberous sclerosis.³

Universal rare disease classifications provide a common language for recording, reporting and monitoring diseases. Please visit the Rare Disease Classifications page for more information about these internationally recognised classifications.

ORPHA:805 Tuberous sclerosis complex

ICD-11: LD2D.2 Tuberous sclerosis

Symptoms and severity of TSC can vary widely between individuals, even between members of the same family.² Signs and symptoms of TSC may depend on the organs that are affected. Growth of benign tumours are common in the brain, kidneys, heart, eyes and lungs. These tumours are usually harmless, but they may grow and compress against nerves, obstruct flow, and affect the organ’s function.^1,2-4

Signs and symptoms of TSC include but are not limited to:^1-5

Skin

• hypomelanotic macules – white spots or patches often on the arms, legs, and trunk
• facial angiofibromas – pink or reddish raised spots on the face
• shagreen patch – thickened and bumpy skin patch, usually on the lower back
• ungual fibromas – lumps around or under the nails

Brain

• structural brain changes, including cortical tubers, and subependymal nodules (SENs) and subependymal giant cell astrocytomas (SEGAs)
• hydrocephalus (increased pressure in the brain, usually from SEGAs blocking the flow of cerebrospinal fluid) and brain damage
• seizures and/or epilepsy
• behavioural attributes, intellectual disability, learning difficulties, autism, and mental health conditions; also collectively known as TSC-associated neuropsychiatric disorders (TAND)

Kidneys

• angiomyolipomas (AMLs) (benign kidney tumours made up of blood vessels, muscle and fat) which can cause life-threatening bleeding and kidney failure
• kidney cysts

Heart

• cardiac rhabdomyomas (benign heart tumours) are commonly detected before birth or in infancy and often decrease in size or resolve over time

Eyes

• retinal hamartomas (benign growths on the retina) are the most common finding and are usually present from birth, typically without affecting vision
• other features may include optic nerve involvement or areas of reduced retinal pigmentation
• cortical visual impairment caused by damage to the part of the brain that process vision

Lungs

• lymphangioleiomyomatosis (LAM) that primarily affects women. It can cause breathing problems, and affect the kidney, uterus and lymphatic system.

Please speak to your medical team to learn more about the symptoms and health implications of TSC.

Rare diseases are often serious and progressive, exhibiting a high degree of symptom complexity, leading to significant disability. Majority of the estimated two million Australians living with a rare disease meet the Australian Government’s definition for disability (in accordance to the Australian Public Service Commission and Australian Bureau of Statistics), and many experience severe and permanent disability impacts. If you or someone you care for is experiencing disability-related impacts from a rare condition, please speak with a health or disability professional for advice. Information about relevant disability support can be found at the RARE Portal’s Disability Support Information page.

TSC is a genetic condition, caused by disease-causing genetic changes (variants) in the TSC1 or TSC2 genes.² TSC1 and TSC2 genes are tumour suppressor genes that prevent cells in the body from growing uncontrollably. They play an important role in a signalling pathway called the mTOR pathway that is essential for regulating cell growth in the body.⁵ Genetic variants in the TSC1 and TSC2 genes disrupt the mTOR pathway, leading to uncontrolled cell growth and development of tumours in various organs.^3,5

In the majority of people with TSC, the genetic variant occurs randomly before birth (de novo) and is not inherited/passed down from their parents.^1,2

In some people, the genetic variant is inherited from their parents in an autosomal dominant manner. Everyone has two copies of each gene, one from their mother, and one from their father. TSC is an autosomal dominant condition, which means that having a genetic variant in just one of the TSC1 or TSC2 gene copies can result in TSC. If a parent has the autosomal dominant gene variant, there is a 50% chance that they will pass that genetic variant to each of their children.² More information on autosomal dominant inheritance can be found at Centre for Genetics Education: Autosomal dominant inheritance.

If you would like to learn more about the inheritance and impact of this condition, please ask your doctor for a referral to a genetic counsellor. Genetic counsellors are qualified allied health professionals who can provide information and support regarding genetic conditions and testing. More information about genetic counselling can be found at:

• Information on Genetic Services
• The National and State Services pages underneath the ‘Genetic Counselling’ sections listed

Diagnosis of TSC may be made based on:^1,4

• physical examination to look for characteristic features in the skin, eyes, brain, lungs, kidneys, teeth and bones
• family history
• genetic testing to look for TSC1 or TSC2 genetic variants
• MRI scans of the brain or abdomen
• blood tests

More information about diagnosis of TSC can be found at Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations developed by the International TSC Consensus Group of medical experts, published in 2021.

Please speak to your medical team to learn more about the available diagnostic pathways for TSC.

There is currently no curative treatment for TSC. Treatment is targeted at managing symptoms (symptomatic management) and involves a multidisciplinary care team. This may include:^1-5

• Medicines that inhibit the mTOR pathway (mTOR inhibitors) to reduce the size of benign tumours
• surgery to remove tumours if it affects the organ’s function
• management of seizures
• behavioural therapy and special education support
• physiotherapy
• occupational therapy
• speech therapy

Regular surveillance and monitoring for multiple organs, including the brain, kidneys, lungs, skin, teeth, heart, and eyes have been recommended for people living with TSC.⁴

Please speak to your medical team to learn more about the possible treatment or management options for your condition. Treatment will depend on an individual’s specific condition and symptoms. It is also important to stay connected to your medical team so that you can be made aware of any upcoming clinical trial opportunities.

Healthcare professionals involved in the care of people with TSC may include general practitioners (GP), paediatricians, cardiologists, neurologists, epileptologists, neurosurgeons, nephrologists, dermatologists, psychiatrists, developmental paediatricians, genetic counsellors, physiotherapists, occupational therapists, and speech therapists.^3,4 The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.

Clinical care for rare diseases often involves a multidisciplinary team of medical, care and support professionals. Please note that the information provided here is as a guide and that RVA does not necessarily monitor or endorse specific clinics or health experts.

For many rare diseases, palliative care services may be relevant and useful. Palliative care services are available for people (adults, children and their families) living with a life-limiting illness and is not only for end-of-life care. It can also help at any stage of illness from diagnosis onwards, and will look different for different people. Palliative care services provide assistance, support, resources and tools to help people manage their illness and the symptoms, ease pain, and improve comfort and quality of life. If this is relevant to you and you wish to find out more information about palliative care and how it can help you, please visit:

• Australian Institute of Health and Welfare: Palliative care Overview
• Australian Government Department of Health, Disability and Ageing: Palliative care
• Palliative Care Australia

We are not aware of any clinical care guidelines for TSC in Australia. If you know of any relevant care guidelines, please let us know via the Contribute page.

The following guidance is available from international experts outside Australia; however, there may be information that is not relevant or applicable to the Australian context, and may not be up to date:

• Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations developed by the International Tuberous Sclerosis Complex Consensus Group of medical experts, published in 2021.

Individuals living with rare diseases may have complex medical issues and disabilities, which are not always visible. It is often useful to refer to their medical history as well as personal information such as a medical card, doctor’s letter, or if available, a rare disease passport, for relevant information.

In addition, individuals, their parents, families and carers often develop extensive expertise on their specific rare disease. It is important to recognise that they can contribute valuable knowledge about their rare condition. Rare diseases often impact individuals differently, so it’s important to consider a person’s lived experience.

Tuberous Sclerosis Australia: Research has information on TSC-related research from Australia and internationally.

There are specific considerations around participating in rare disease research, including clinical trials. It is important to be mindful of issues such as data privacy, research ethics, consent and differences in research regulations between Australia and other countries. For more information, please visit the RARE Portal’s Considerations for Participating in Health and Medical Research page.

If you are interested in finding clinical trials for your condition, please visit the following websites; however, there may not be any clinical trials available:

• Australian Clinical Trials
• ClinicalTrials.gov

It is best to discuss your interest in research, including clinical trials,  with your medical team to determine suitability and eligibility.

Australian Organisation:
Tuberous Sclerosis Australia
Website: https://tsa.org.au/
Tuberous Sclerosis Australia (TSA) is an Australian charitable organisation that supports people with TSC. They provide information, advice and support for anyone in Australia that is affected by TSC.

Please note that RVA does not monitor or endorse each group/organisation’s operational governance and activities. When engaging with a group, please consider the information on the RARE Portal’s Finding Helpful Peer and Community Supports page.

TSC varies between individuals, and each person’s experience is unique.

Personal story shared with RVA: Jemima’s story

If you would like to share your personal story with RVA, please visit the Rare Voices Australia: Share Your Story page. RVA will consider your story for publishing on our website and inclusion on the RARE Portal.

Tuberous Sclerosis Australia: Find Support has information on financial, school, peer support, and resources for people living with TSC.

Tuberous Sclerosis Australia: National Disability Insurance Scheme (NDIS) Resources

Tuberous Sclerosis Australia also operates a telehealth nurse service that provide TSC information and support to people living with TSC in Australia.

For information on available government and social services that provide support for individuals with a rare disease, please visit the National and State Services pages.

People living with a rare disease often face unique challenges such as diagnostic delays, misdiagnoses, limited treatment options, and limited access to rare disease specialists and support. These challenges may impact people’s emotional wellbeing and quality of life. Many find it helpful to seek mental health and wellbeing support to cope with ongoing stress and uncertainty. Connecting with people who have shared experiences through a support group may also be helpful. Information about relevant mental health and wellbeing support can be found at:

• Mental Health and Wellbeing Support for Australians Living with a Rare Disease
• The National and State Services pages underneath the ‘Mental Health’ sections listed

Further information on TSC can be found at:

• Healthdirect: Tuberous sclerosis
• Genetic and Rare Diseases (GARD) Information Center: Tuberous sclerosis
• National Organisation for Rare Disorders (NORD): Tuberous Sclerosis
• Tuberous Sclerosis Australia: Surveillance and Screening

Tuberous Sclerosis Australia: For Health Care Professionals

Tuberous Sclerosis Australia: Managing Tuberous Sclerosis Complex (TSC) Across the Lifespan

GeneReviews®: Tuberous Sclerosis Complex

Online Mendelian Inheritance in Man, OMIM^® :#191100 Tuberous Sclerosis 1; TS1

Online Mendelian Inheritance in Man, OMIM^®: #613254 Tuberous Sclerosis 2; TS2

Orphanet: Tuberous sclerosis complex

This page has been co-developed by Rare Voices Australia (RVA)’s RARE Portal team in consultation with Tuberous Sclerosis Australia.

If you are aware of any additional information that may benefit stakeholders with an interest in this page, or if you notice any broken links or inaccurate information, please let us know via the Contribute page.