Tuberous sclerosis complex is caused by mutations in a gene.
Children may have abnormal skin growths, seizures, delayed development, learning disorders, or behavioral problems and may be intellectually impaired or autistic.
Life expectancy is usually unaffected.
Because the disorder is lifelong and new problems can develop, people must be monitored for their entire life.
The diagnosis is based on established criteria, symptoms, imaging tests, and sometimes genetic tests.
Treatment is focused on relieving symptoms.
Tuberous sclerosis complex is a neurocutaneous syndrome. A neurocutaneous syndrome causes problems that affect the brain, spine, and nerves (neuro) and the skin (cutaneous).
In tuberous sclerosis complex, tumors or other abnormal growths develop in several organs, such as the brain, heart, lungs, kidneys, eyes, and skin. The tumors are usually noncancerous (benign). The disorder is named for the typical long and narrow tumors in the brain, which resemble roots or tubers.
Tuberous sclerosis complex is usually present at birth, but symptoms may be subtle or take time to develop, making the disorder difficult to recognize early.
In most cases, the disorder results from mutations in one of two genes. If either parent has the disorder, children have a 50% chance of having it. However, tuberous sclerosis complex often results from spontaneous—new (not inherited)—mutations in the gene, rather than an inherited abnormal gene. This disorder occurs in 1 in 6,000 children.
Symptoms of Tuberous Sclerosis Complex
Symptoms of tuberous sclerosis complex vary greatly in severity.
Tuberous sclerosis may affect the brain and cause seizures Seizures in Children Seizures are a periodic disturbance of the brain’s electrical activity, resulting in some degree of temporary brain dysfunction. When older infants or young children have seizures, they often... read more , intellectual disability Intellectual Disability Intellectual disability is significantly below average intellectual functioning present from birth or early infancy, causing limitations in the ability to conduct normal activities of daily... read more , autism Autism Spectrum Disorders Autism spectrum disorders are conditions in which people have difficulty developing normal social relationships, use language abnormally or not at all, and show restricted or repetitive behaviors... read more , delayed development of motor or language skills, learning disorders Learning Disorders Learning disorders involve an inability to acquire, retain, or broadly use specific skills or information, resulting from deficiencies in attention, memory, or reasoning and affecting academic... read more , and behavioral problems Overview of Behavioral Problems in Children Children acquire many skills as they grow. Some skills, such as controlling urine and stool, depend mainly on the level of maturity of the child's nerves and brain. Others, such as behaving... read more (such as hyperactivity and aggression).
The first symptom of tuberous sclerosis complex may be infantile spasms Infantile Spasms In infantile spasms, children suddenly raise and bend their arms, bend their neck and upper body forward, and straighten their legs. The spasms are usually caused by serious brain disorders... read more , a type of seizure.
The skin is often affected, sometimes causing disfigurement:
Light-colored, ash-leaf–shaped patches may appear on the skin during infancy or early childhood.
Rough, raised patches resembling orange peel (shagreen patches), usually on the back, may be present at birth or develop later.
Medium-brown, flat spots that are the color of coffee with milk (café-au-lait spots) may also develop.
Red lumps consisting of blood vessels and fibrous tissue (angiofibromas) may appear on the face later during childhood (called adenoma sebaceum).
Small fleshy bumps (fibromas) may grow around and under the toenails and fingernails (Koenen tumors) at any time during childhood or early adulthood.
Before birth, benign heart tumors called rhabdomyomas may develop. Sometimes these tumors cause heart failure in newborns. These tumors typically disappear over time and do not cause symptoms later in childhood or in adulthood.
In many children, permanent teeth are pitted.
Patches and benign tumors may develop on the retina, located at the back of the eye. If the patches or tumors are located near the center of the retina, vision may be affected.
Tubers in the brain may become tumors, which sometimes become cancerous, and enlarge, causing headaches or making other symptoms worse.
During adulthood, cancerous kidney tumors may develop, and polycystic kidney disease Polycystic Kidney Disease (PKD) Polycystic kidney disease is a hereditary disorder in which many fluid-filled sacs (cysts) form in both kidneys. The kidneys grow larger but have less functioning tissue. Polycystic kidney disease... read more may develop at any age. These disorders may cause high blood pressure, abdominal pain, and blood in the urine.
Solid, raised areas (nodules) may develop in the lungs, particularly in adolescent girls. This condition is called lymphangioleiomyomatosis Lymphangioleiomyomatosis Lymphangioleiomyomatosis (LAM) is a rare, slowly progressive growth of smooth muscle cells throughout the lungs. (See also Overview of Interstitial Lung Diseases.) Lymphangioleiomyomatosis ... read more .
Diagnosis of Tuberous Sclerosis Complex
A doctor's evaluation
Magnetic resonance imaging or ultrasonography
Sometimes genetic testing
Doctors can use an established set of criteria to help them diagnose tuberous sclerosis complex (for more information, see diagnosis of tuberous sclerosis). Before they apply the criteria, doctors first do a physical examination to determine whether people have certain symptoms, such as seizures, delayed development, or typical skin changes.
Sometimes tuberous sclerosis complex is suspected when routine prenatal ultrasonography Ultrasonography Prenatal diagnostic testing involves testing the fetus before birth (prenatally) to determine whether the fetus has certain abnormalities, including certain hereditary or spontaneous genetic... read more detects a tumor in the heart or brain. Magnetic resonance imaging (MRI) Magnetic Resonance Imaging (MRI) In magnetic resonance imaging (MRI), a strong magnetic field and very high frequency radio waves are used to produce highly detailed images. MRI does not use x-rays and is usually very safe... read more or ultrasonography is done to check for tumors in various organs.
An eye examination (with ophthalmoscopy Ophthalmoscopy A person who has eye symptoms should be checked by a doctor. However, some eye disorders cause few or no symptoms in their early stages, so the eyes should be checked regularly (every 1 to 2... read more ) is done to check for eye abnormalities.
Genetic testing may be done for the following reasons:
To confirm the diagnosis when symptoms suggest it
To determine whether people who have a family history of the disorder but who do not have symptoms have the abnormal gene
To check for the disorder before birth (prenatal diagnosis) if the family history includes the disorder
Prognosis for Tuberous Sclerosis Complex
How well affected people do depends on how severe the symptoms are. If symptoms are mild, infants generally do well and grow up to live long, productive lives. If symptoms are severe, infants may have serious disabilities.
Nonetheless, most children continue to develop, and life expectancy is usually unaffected.
Treatment of Tuberous Sclerosis Complex
Treatment of symptoms and complications
Sirolimus or everolimus
Treatment of tuberous sclerosis complex is focused on relieving symptoms:
For seizures: Antiseizure drugs Antiseizure drugs In seizure disorders, the brain's electrical activity is periodically disturbed, resulting in some degree of temporary brain dysfunction. Many people have unusual sensations just before a seizure... read more may be used. Sometimes if drugs are ineffective, surgery is done to remove a tumor or to remove a small part of the brain that is involved in causing the seizures.
For high blood pressure: Antihypertensive drugs may be used, or surgery may be done to remove kidney tumors.
For behavioral problems: Behavior management techniques (including time-outs The time-out technique Children acquire many skills as they grow. Some skills, such as controlling urine and stool, depend mainly on the level of maturity of the child's nerves and brain. Others, such as behaving... read more and consistent use of appropriate consequences and praise) may help. Sometimes drugs are needed.
For developmental delays: Special schooling or physical therapy Physical Therapy (PT) Physical therapy, a component of rehabilitation, involves exercising and manipulating the body with an emphasis on the back, upper arms, and legs. It can improve joint and muscle function, helping... read more , occupational therapy Occupational Therapy (OT) Occupational therapy, a component of rehabilitation, is intended to enhance a person's ability to do basic self-care activities, useful work, and leisure activities. These activities include... read more , or speech therapy Overview of Rehabilitation Rehabilitation services are needed by people who have lost the ability to function normally, often because of an injury, a stroke, an infection, a tumor, surgery, or a progressive disorder ... read more may be recommended.
For skin growths: They may be removed with dermabrasion (rubbing the skin with an abrasive metal instrument to remove the top layer) or lasers Using Lasers to Treat Skin Problems .
For cancerous tumors and some noncancerous tumors: Everolimus can be used to shrink the tumors, including rhabdomyomas in newborns.
Sirolimus and everolimus are being studied to determine whether they can effectively treat or prevent some of the complications of tuberous sclerosis complex. In some people, these drugs taken by mouth have been shown to shrink brain and heart tumors and facial growths and to lessen seizures. Sirolimus applied to the skin may be helpful for skin growths on the face. These drugs are currently used to treat certain cancers and to prevent rejection of transplanted organs.
Genetic counseling is recommended for affected people and family members when they are considering having children.
Screening for new problems
Because tuberous sclerosis complex is a lifelong disorder and new problems can develop, affected people must be closely monitored for the rest of their life.
Monitoring typically includes the following:
MRI of the head
Ultrasonography or MRI of the abdomen to check for kidney tumors
Periodic computed tomography (CT) scan of the chest for women age 18 and older
Echocardiography (scan of the heart using ultrasound)
Detailed testing of mental function (neuropsychologic testing) for children to help plan for support at school and behavior management