Tuberous sclerosis complex: what it is, symptoms, genetics and treatment

TSC is a genetic condition, which means a person is born with it. The TSA says it cannot be developed over time and cannot be caught from another person, but problems from TSC might not become obvious until later in life. It causes non-cancerous growths to develop in different organs around the body, and the issues it causes are the result of those growths.

The effects vary from person to person, even within one family. Some people have few problems and may not even know they have TSC, while others need much more specialist care and were diagnosed from birth. The TSA lists epilepsy, autism, learning difficulties and kidney problems as the common ones.

The NHS website does not have a dedicated page for TSC, so this guide draws mainly on the TSA, the UK charity for the condition, which publishes a summary of the UK clinical guidelines for TSC.

There is no single set of symptoms, because TSC can affect many parts of the body and different people have different combinations. The table summarises the main areas covered in the TSA pages. Not everyone is affected in every area.

On the skin, the TSA lists ash leaf marks (present at birth), facial angiofibromas (usually from age 2 to 5, sometimes worsening at puberty), shagreen patches (throughout childhood and adolescence) and growths around and under the nails (usually in adulthood). It says the biggest impact of skin marks is often psychological.

TSC is caused by mutations in two genes, TSC1 and TSC2. The TSA says that people with a TSC2 mutation are generally, but not always, more strongly affected than those with a TSC1 mutation.

Around one in three people with TSC inherited it from a parent who also has it. The TSA explains this as dominant inheritance, with a 50 percent chance in every pregnancy that the child inherits it, regardless of the sex of either person. In around two in three people neither parent shows signs, because the change was a random, sporadic mutation.

In around 2 percent of cases, the TSA says couples have a second child with TSC after a first child with a non-inherited form, which is explained by germline mosaicism, where the change is present in only some egg or sperm cells. Some people also have somatic mosaicism, with the change in only some body cells, and some research suggests people with mosaic TSC are less likely to have as many seizures or cortical tubers.

The TSA lists common first signs: heart tumours found before birth or in newborns, a toddler missing developmental milestones, seizures including infantile spasms in newborns, ash leaf skin marks in children and adolescents, kidney problems in adults, and a diagnosis in a child that leads to testing a parent or sibling. It stresses that no single feature is absolutely specific to TSC.

It advises that parents who think a child may be having infantile spasms should seek medical help as soon as possible. In an emergency, such as a prolonged seizure, call 999.

The TSA says diagnosis can happen at any age, from before birth to adulthood.

The TSA says diagnosis follows careful examination combined with scans and, increasingly, genetic testing. Clinicians may use a checklist of characteristic features, including skin changes or growths in the eyes, brain, heart, lungs or kidneys. UK clinical guidelines for diagnosis and management were released in 2018.

Tests the TSA lists include an MRI scan of the brain, a CT scan of the lungs, liver and kidneys, ultrasound of the kidneys, an echocardiogram of the heart, an eye examination, a skin examination under ultraviolet light and genetic testing. The TSA says genetic testing is correct in around 80 percent of cases.

A person diagnosed will possibly be referred to a specialist NHS TSC clinic, with follow-up scans and referral to specialists such as a neurologist.

The TSA says there is currently no cure for TSC, but a broad range of treatments and therapies allows many people to manage its effects. Treatment depends on how the condition is affecting the individual and may include medicines, operations and, for the skin, creams, laser therapy and surgery. It aims to reduce the size and spread of growths such as a SEGA in the brain or kidney AMLs, the number and severity of seizures, the spread of skin lesions, and the impact of TAND.

For kidney AMLs, the TSA says treatment can include embolisation (blocking blood flow to the growths), surgery or medication such as everolimus, and that in very rare cases dialysis or transplantation may be considered. For skin, everyone with TSC-related skin problems should wear sunscreen and keep out of the sun.

Monitoring matters because growths can change over time. The TSA says scans and examinations take place at set intervals, such as every six months or annually, as a clinician directs. For the kidneys it says monitoring by MRI or CT every 1 to 3 years is typical, with annual blood pressure and kidney function checks. Which treatments are suitable is decided by the specialist team and depends on the individual.

The TSA says epilepsy is the most common neurological feature of TSC and is thought to occur because of cortical tubers, disorganised areas of the brain. It often begins in the early years or childhood, but can begin in adults, and people with TSC often develop different seizure types as they age. Focal seizures are the most common.

Outcomes vary enormously. Some children and adults respond quickly to medicine, although around one in two of these children later begin to have different seizures. Parents who think a child may be having infantile spasms should seek medical help as soon as possible. In an emergency, such as a prolonged seizure, call 999.

The TSA says the way TSC affects a life varies considerably. With better understanding of the condition, most people can expect to live healthier lives with a normal life expectancy. Many people with TSC-related epilepsy live fulfilling lives with a few changes to their daily routines.

People with skin changes should wear sunscreen and avoid the midday sun. The TSA runs a support line and publishes information for families, including on how to be referred to an NHS TSC clinic.

The TSA says there are specialist NHS TSC clinics throughout the UK and that a person with TSC will probably be referred to one, based on their location and the care they need. Staff in these clinics understand how complicated TSC is and how differently it affects each person, and are aware of the UK clinical guidelines.

Private neurology, nephrology or genetic testing can supplement this, for example by arranging an MRI more quickly, but long-term monitoring is usually best coordinated through a TSC clinic. Ask any private provider to share results with the clinic.