Tuberous sclerosis complex is a hereditary disorder that causes abnormal growths in the brain, changes in the skin, and sometimes tumors in vital organs, such as the heart, kidneys, and lungs.
Tuberous sclerosis complex is caused by mutations in a gene.
Children may have abnormal skin growths, seizures, delayed development, learning disorders, autism, or behavioral problems and may be intellectually impaired.
The diagnosis is based on established criteria, symptoms, imaging tests, and sometimes genetic tests.
Treatment is focused on relieving symptoms.
Because the disorder is lifelong and new problems can develop, people must be monitored for their entire life.
Life expectancy is usually unaffected.
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 1 of 2 genes. If either parent has the disorder, children have a 50% chance of having it. However, tuberous sclerosis complex usually results from spontaneous, new (not inherited) mutations in 1 of the 2 genes, rather than from 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, intellectual disability, autism, delayed development of motor or language skills, learning disorders, and behavioral problems (such as hyperactivity and aggression).
The first symptom of tuberous sclerosis complex may be infantile spasms, 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 bumps 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.
This photo shows an ash-leaf–shaped patch. These patches appear on many people who have tuberous sclerosis complex.
By permission of the publisher. From Puduvalli V: Atlas of Cancer. Edited by M Markman and R Gilbert. Philadelphia, Current Medicine, 2002.
This photo shows bumps consisting of blood vessels and fibrous tissue (angiofibromas) on the face of a person who has tuberous sclerosis complex.
DR M.A. ANSARY/SCIENCE PHOTO LIBRARY
This photo shows red bumps consisting of blood vessels and fibrous tissue (angiofibromas) across the middle of the face of a person with tuberous sclerosis complex.
Photo courtesy of Karen McKoy, MD.
This photo shows small fleshy bumps (fibromas) that grow around and under the toenails and fingernails (Koenen tumors) in people who have tuberous sclerosis complex.
© Springer Science+Business Media
This photo shows an ash-leaf–shaped patch. These patches appear on many people who have tuberous sclerosis complex.
By permission of the publisher. From Puduvalli V: Atlas of Cancer. Edited by M Markman and R Gilbert. Philadelphia, Current Medicine, 2002.
This photo shows bumps consisting of blood vessels and fibrous tissue (angiofibromas) on the face of a person who has tuberous sclerosis complex.
DR M.A. ANSARY/SCIENCE PHOTO LIBRARY
This photo shows red bumps consisting of blood vessels and fibrous tissue (angiofibromas) across the middle of the face of a person with tuberous sclerosis complex.
Photo courtesy of Karen McKoy, MD.
This photo shows small fleshy bumps (fibromas) that grow around and under the toenails and fingernails (Koenen tumors) in people who have tuberous sclerosis complex.
© Springer Science+Business Media
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 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.
Diagnosis of Tuberous Sclerosis Complex
Established criteria
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. 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 before birth when routine prenatal ultrasonography detects a tumor in the heart or brain. Magnetic resonance imaging (MRI) or ultrasonography is done to check for tumors in various organs.
An eye examination (with ophthalmoscopy) 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 an abnormal gene
To check for the disorder before birth (prenatal diagnosis) if the family history includes the disorder
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 medications may be used. If these medications are not effective, sometimes 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 medications may be used, or surgery may be done to remove kidney tumors.
For behavioral problems: Behavior management techniques (including time-outs and consistent use of appropriate consequences and praise) may help. Sometimes medications are needed.
For developmental delays: Special schooling or physical therapy, occupational therapy, or speech therapy 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.
Sirolimus applied to the skin may be helpful for skin growths on the face. These medications 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 of the kidneys 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
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 severe disabilities.
Nonetheless, most children continue to progress developmentally, and life expectancy is usually unaffected.
