Tuberous sclerosis is a neurocutaneous disorder involving the brain and spinal cord (central nervous system) as well as the skin. In addition, this genetic condition also affects other parts of the body. This multisystem disease causes multiple, often benign, tumors to develop in different parts of the body. The name is derived from the characteristic tuberous or potato-like (tuberous) brain growths that harden or sclerose with age. Various imaging and other tests reveal the presence of the disease. The treatment of tuberous sclerosis is multidisciplinary, with the doctor and other healthcare providers combating the symptoms and increasing the quality of life. The severity and course of the rare disease cannot be predicted, but thanks to good support and care, many patients lead productive lives.
- Synonyms tuberous sclerosis
- Epidemiology neurocutaneous disorder
- Causes
- Symptoms and tumors of the brain, skin and kidneys
- Diagnosis and examinations
- Therapy
- Prognosis is variable
- Complications disease
Synonyms tuberous sclerosis
Tuberous sclerosis is also known by these synonyms:
- adenoma sebaceum
- epiloia
- Bourneville’s disease
- Pringle-Bourneville disease
- tuberous sclerosis complex (TS or TSC)
Epidemiology neurocutaneous disorder
Approximately 1 in 6,000 babies are born each year with tuberous sclerosis. The prevalence is 1 in 10,000 inhabitants. Worldwide, approximately one million patients suffer from the multisystem disorder. The actual frequency may be higher because many parents with mild or no symptoms do not undergo diagnostic testing and the recognition of many patients with mild symptoms. The disease affects people of all races. Men and women are affected by tuberous sclerosis in equal numbers.
Causes
Tuberous sclerosis is an autosomal dominant hereditary disorder in which mutations (changes) occur in two genes (TSC1 and TSC2). In tuberous sclerosis, one mutated gene from a parent is enough to produce a child with this disease. The chance of getting the disease is 50%. Tuberous sclerosis usually arises as a result of a new mutation (de novo), in which there is no family history of the disease.
Symptoms and tumors of the brain, skin and kidneys
Tuberous sclerosis is a hereditary condition involving abnormalities in the brain, skin, kidneys, eyes, heart and lungs in combination with behavioral problems. Tuberous sclerosis occurs at birth although symptoms are not always immediately apparent. The symptoms are expressed quite subtly during the first years of life. It is true that the symptoms are different in every patient and vary widely from very mild to very severe. Some patients even have no intellectual disability and normal intelligence.
Brain
Signs that the condition is affecting the brain include:
- calcium deposits in the brain
- an intellectual disability
- delayed development
- hydrocephalus (too much cerebrospinal fluid in the skull) with symptoms: feeling ill, headache, difficulty walking, neck pain, increasing drowsiness, loss of bladder and bowel control, confusion, blurred vision, double vision or vision loss
- epileptic attacks
- behavioral problems such as aggression, anxiety, depression, extreme shyness, hyperactivity, autism spectrum disorder (autism: problems with social interaction, communication and behavior) or sleep disorders
- brain tumors
develops in ±60% of patients and mild to moderate intellectual disability develops in ±40% of patients.
Skin
The skin-related symptoms include:
- areas of the skin that turn white (due to reduced pigment) and have an ash leaf or confetti-shaped appearance.
- skin tumors
- red spots on the face that contain many blood vessels (adenoma sebaceum)
- raised spots on the skin with the texture of an orange peel (shagreen spots), often on the back
Kidneys
Kidney problems occur in approximately 70-80% of patients, often between the ages of fifteen and thirty. These kidney-related symptoms occur:
- angiomyolipomas in the kidneys (benign growths made up of fatty tissue and muscle cells) causing kidney failure or bleeding resulting in bleeding, anemia and low blood pressure (hypotension) which is a medical emergency
- severe renal impairment
- renal cell carcinoma (kidney cancer)
- kidney cysts (polycystic kidney disease)
Tumors
The disease is also characterized by tumors that can grow in almost any organ. These often benign growths most often occur in the brain, kidneys, heart (rhabdomyoma), lungs, on the skin, on the tongue or gums and in the eyes (hamartomas on the retina with pale spots in the eye as consequence). Other places where tumors occur are the liver, lungs, pancreas, bone and rectum. Even rough growths under or around the fingernails and toenails are possible. Malignant tumors are rare in tuberous sclerosis. If these do occur, they are usually found in the kidneys.
Other symptoms
Other symptoms also occur with tuberous sclerosis:
- breathing problems
- an abnormal heart rhythm (dysrhythmia)
- pits in the tooth enamel
Diagnosis and examinations
Diagnostic research
After a thorough physical examination, the doctor carries out several examinations:
- A DNA test that detects one of the two genes that causes the disease
- An ultrasound, CT scan and MRI scan of the head, heart, kidneys and lungs to detect tumors
- An electrocardiogram (ECG) to detect abnormal electrical activity in the heart (caused by heart tumors)
- An electroencephalogram (EEG) detects abnormal electrical activity in the brain (present in epilepsy)
- An eye examination to detect eye tumors and white spots on the retina (vision is often not affected by the disease)
- An ultraviolet light examination of the skin to look for white spots, thickened skin, or other skin abnormalities
Differential diagnosis
The following conditions mimic many symptoms of tuberous sclerosis and are therefore known as the differential diagnosis for tuberous sclerosis:
- complex partial seizures
- an intellectual disability
- hydrocephalus (hydrocephalus)
- glioblastoma multiforme
- the Lennox-Gastaut syndrome (severe form of epilepsy)
- infantile spasms (West syndrome)
Therapy
Tuberous sclerosis cannot be cured, but the doctor applies supportive treatment. Special education is sometimes necessary for a patient with an intellectual disability. Attacks can be treated with medication or surgery. The doctor removes small growths on the face (adenoma sebaceum) using laser treatment. These growths often return, requiring repeat treatment. Rhabdomyomas (heart tumors) usually disappear after puberty, so surgery is not always necessary to remove them. Brain tumors, kidney tumors and lung tumors can be treated with medication and/or surgery. The doctor also treats the behavioral problems with medications and therapies. Furthermore, a patient regularly needs various examinations to detect changes in the organs in time.
Prognosis is variable
The outlook for the chronic condition tuberous sclerosis is highly variable and dependent on the severity of symptoms. Children with mild tuberous sclerosis have a fairly good prognosis. However, when severe intellectual disability or uncontrollable seizures are present, the outlook is less good. The tumors associated with this disease are often benign, but kidney or brain tumors sometimes develop into cancer.
Complications disease
Complications of tuberous sclerosis include:
- bronchopneumonia (inflammation of the trachea and lungs)
- a severe intellectual disability
- heart failure (poor pumping of blood by the heart)
- kidney failure
- uncontrollable seizures (status epilepticus)
- vision problems (rare)
The most common causes of death are brain complications (epilepsy, hydrocephalus, brain tumor), kidney, heart and lung failure.