What Are the Signs and Symptoms of Tuberous Sclerosis Complex?

Tuberous sclerosis is an uncommon genetic disorder which is thought to affect about one in 6,000 to 10,000 people. The condition is also known as tuberous sclerosis complex (TSC), and can affect many different parts of the body and can vary widely in its severity between individuals. Below, explain what tuberous sclerosis is, the signs and symptoms, treatment options and where to get support if you or a loved one is living with TSC.

What Is Tuberous Sclerosis?

Tuberous sclerosis is a complex and uncommon genetic condition which can have varying levels of severity from person to person. Some people have severe symptoms and complications as a result of the condition and are diagnosed early in their life. Others do not even know they have it until they undergo genetic testing because their child or a close relative is diagnosed. 

Tuberous sclerosis is characterised by the growth of benign (non-cancerous) tumours or overgrowths of normal tissue to grow in different parts of the body. Signs and symptoms of tuberous sclerosis can vary widely depending on the extent of the growths and whereabouts in the body they take place. Tuberous sclerosis growths often occur in the brain, as well as the heart, lungs, liver, kidneys and eyes. There is currently no known cure for tuberous sclerosis, but medical advancements have created effective treatment and management options which can usually alleviate symptoms and allow people with tuberous sclerosis to lead normal lives. 

What Causes Tuberous Sclerosis?

Tuberous sclerosis is a genetic condition which is caused by a mutation in one of two genes: TSC1 or TSC2. When a change in either of these two genes occurs, the cell growth in normal tissue can become uncontrolled and lead to the growth of benign tumours. About two-thirds of people with tuberous sclerosis have no family history of TSC and developed the condition due to a random cell mutation. In about one-third of cases of tuberous sclerosis, the individual inherited a mutated TSC1 or TSC2 from a parent. People with tuberous sclerosis have about a 50% likelihood of passing the condition onto their children. 

What Are the Signs and Symptoms of Tuberous Sclerosis?

The signs and symptoms of tuberous sclerosis are heavily dependent on where uncontrolled cell growth takes place within the body. Below are some of the key signs and symptoms of tuberous sclerosis that can occur in the brain, eyes, heart, lungs, kidneys and skin.

Effects of Tuberous Sclerosis on the Skin

The skin is the most commonly affected organ in individuals with tuberous sclerosis. Almost everyone with tuberous sclerosis will experience at least one symptom relating to their skin. Signs and symptoms in the skin are often the first sign that a person may have tuberous sclerosis. Signs and symptoms to be aware of include:

• White spots (hypomelanotic macules) on the skin are present in almost every individual with tuberous sclerosis. They may appear at birth and are usually present for the entire lifespan of the individual affected. They can appear anywhere on the body but are most commonly seen in the limbs, torso and glutes.
• Facial angiofibromas – red, pink, or flesh coloured bumps that are scattered across the face, especially the nose and cheeks.
• Forehead fibrous plaque – similar to angiofibromas but often larger and usually found on the forehead.
• Shagreen patch – a patch of skin with thick, pebbled skin that resembles an orange peel. It is made up of tissue similar to scar tissue, and is usually on the lower back but sometimes also on the buttocks and thighs.
• Nail lesions – fibrous growths around the fingernail and toenails. 

Effects of Tuberous Sclerosis on the Brain

The brain is one of the more commonly affected organs in individuals with tuberous sclerosis. Most individuals diagnosed with tuberous sclerosis have at least some signs of TSC in the brain. These impacts can range from very mild to very severe, and often include

• Tubers (growths) in the cortical and subcortical areas of the brain
• Subependymal nodules (SEN) – small accumulations of cells located on the walls of the cerebral ventricles  
• Subependymal giant cell astrocytomas (SEGAs) – low-grade glioneuronal tumours in the brain.

These tumours can create additional complications, including

• Epilepsy
• Other TSC Associated Neuropsychiatric Disorders (TAND) including
  • Behavioural challenges
  • Intellectual disability
  • Autism
  • Learning difficulties
  • Poor mental health 
  • Developmental delays
  • Hyperactive tendencies
  • Sleeping difficulties

Effects of Tuberous Sclerosis on the Eyes

About half of all people with tuberous sclerosis have some signs or symptoms in their eyes. Vision loss is not a common side effect of tuberous sclerosis, but other impacts on the eyes are common. These can include

• Retinal hamartomas – Non-cancerous tumours or lesions in the retina which are either smooth-surfaced (known as noncalcified hamartomas) or shaped like a mulberry (calcified hamartomas). These lesions usually do not cause vision loss and require treatment only in severe cases.
• Retinal hypopigmented lesions – white patches located on the retina which look similar to the patches often seen in the skin of people with tuberous sclerosis. 
• Angiofibromas around the eyes – a benign growth of blood vessels and connective tissue that often look like small red bumps. These often occur in the skin but can also appear in the eye area in some cases.
• Vision problems caused by intellectual impairment – vision loss is uncommon in people with tuberous sclerosis, but in some cases, seizures or brain lesions impair the brain’s ability to interpret messages from the eyes, a condition known as a cortical vision impairment (CVI).
• Vision problems as a result of epilepsy treatment – surgical and medical interventions for epilepsy as a result of tuberous sclerosis can in some cases cause damage to the eye which can impair vision. Your neurologist should explain these risks in detail when recommending any potential epilepsy treatment.

Effects of Tuberous Sclerosis on the Heart

Tuberous sclerosis leads to the growth of at least one tumour in the heart in around 50% of cases. These non-cancerous growths are known as cardiac rhabdomyoma and usually do not create any specific symptoms. In some cases, cardiac rhabdomyoma can be detected during pregnancy during routine antenatal ultrasounds, but in some cases can not be seen until the latter half of pregnancy. Cardiac rhabdomyoma is often one of the earlier signs that a baby may have tuberous sclerosis. In many cases, these growths on the heart remain smaller and have no symptoms. In other cases, larger or more numerous growths may lead to signs such as:

• Obstructed blood flow to the heart
• Cyanosis (blue tinge to the skin)
• Cardiomyopathy (poor function of the cardiac muscle)
• Arrhythmia (abnormal heart rhythm)
• Heart murmur (only in rare cases)
• Heart failure (in serious cases with larger or several cardiac rhabdomyoma)

Effects of Tuberous Sclerosis on the Lungs

Growths on the lungs can occur in individuals with tuberous sclerosis. It is more commonly seen in women than men, so women are encouraged to have scans of their chest to determine if any growths appear on the lungs. In many cases, tubers on the lungs will not create any symptoms. Some symptoms that may occur can include:

• Lymphangioleiomyomatosis (LAM) – abnormal growth of smooth muscle cells leading to holes or cysts in the lungs
• Multifocal micronodular pneumocyte hyperplasia (MMPH) – small nodules on the lung tissue
• Other lung conditions and infections such as asthma, pneumonia and influenza

Effects of Tuberous Sclerosis on the Kidneys

Many people with tuberous sclerosis will experience symptoms in their kidneys. With proper lifelong surveillance and treatment for tuberous sclerosis, kidney function can be protected to allow individuals to lead a normal life. Kidney disease can sometimes be an early clue that an individual may have tuberous sclerosis. Tuberous sclerosis can create kidney symptoms including

• Impaired kidney function
• Cysts on the kidneys and/or polycystic kidney disease
• Kidney cancer
• Angiomyolipomas (AMLs) – benign tumours made up of blood, muscle and fat tissue. Around 80% of people with tuberous sclerosis will experience AMLs. AMLs can be serious when they bleed, a symptom which is rare but serious. People with bleeding AMLs may experience pain in their back or abdomen which may or may not be accompanied by blood in the urine.

How Is Tuberous Sclerosis Diagnosed?

There is no definitive test to determine if an individual has tuberous sclerosis. Getting a diagnosis of tuberous sclerosis can be challenging and time consuming because many of its symptoms are similar to those of many other conditions. Getting a diagnosis often depends on whether your doctor observes enough signs and symptoms to confirm that they are a result of tuberous sclerosis. 

Sometimes a diagnosis is made before a baby is born if tumours on the heart are found during routine pre-birth scans. If a close relative is diagnosed with tuberous sclerosis, it can be a good idea to get tested to determine if the condition was randomly acquired or inherited. Tests for diagnosis of tuberous sclerosis include:

• Physical examination
• Eye examinations to determine if there are retinal signs and symptoms
• Computerised tomography (CT) scans or magnetic resonance imaging (MRI) to locate any brain growths
• Renal ultrasound to find any growths on the kidneys
• Scans and test for other organs including the heart and lungs to determine if there are any benign tumours present

When to see your doctor

Tuberous sclerosis is highly individual. Some people with TSC lead a normal life and experience very few symptoms, while others will be more highly affected. Some individuals will be diagnosed with tuberous sclerosis at birth, while for others no signs or symptoms are found until childhood or even adulthood. If you notice any of the signs and symptoms of tuberous sclerosis in your child it is important to notify your paediatrician as soon as possible. Ongoing monitoring of tuberous sclerosis is important to minimise damage to important organs in your body and prevent serious complications like heart complications, kidney damage, lung failure, excess fluid in the brain, vision damage and even greater risk of malignant (cancerous) tumours. If your child, parent or close relative is diagnosed with tuberous sclerosis, it is a good idea to get tested to determine if it is hereditary. 

How Is Tuberous Sclerosis Treated?

There is no cure available for tuberous sclerosis, but there is a range of treatments that are effective at managing its signs and symptoms. Treatment options are individualised and will depend on the organs that are affected. Treatment options may include

• mTOR inhibitor medicine – a relatively new class of medical treatment which is used to treat brain tumours, kidney tumours and epilepsy caused by tuberous sclerosis
• Anti-epileptic medicines – to treat seizures caused by tuberous sclerosis in the brain. These medications need to be carefully monitored to ensure the dose is not too high
• Brain surgery – is used in some cases to remove lesions on the brain that do not respond to medication to reduce seizures
• Skin treatments – surgical and medical options can be recommended by a dermatologist, including the prescription of mTOR inhibitor topical creams
• Occupational therapy – can assist children and adults with neural or cognitive difficulties to develop skills and strategies in their daily life
• Speech therapy – to assist with communication

Getting Support to Manage Your Condition

Living with a genetic condition can be a stressful and challenging experience. Don’t try to manage all of the ups and downs of monitoring your tuberous sclerosis on your own. You can get support and information from your trusted General Practitioner or family doctor, or paediatrician if you have concerns about your child. 

Being informed can help you to feel more empowered to manage your condition or that of a loved one. When you are ready, you can find a range of useful and informative resources on the Tuberous Sclerosis Australia (TSA) website. They also have a TSA Nurse service, which you can access by calling 1300 733 435. Their service is confidential and allows you to ask a qualified nurse any questions you may have about your diagnosis or that of someone you love and care for. 

The Genetic Alliance Australia also provides a range of peer support services in the form of seminars, support groups and counselling. You can access their support services via their website or by calling them on (02) 9295 8359.

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