Tuberous sclerosis is a group of two genetic disorders characterized by problems with the skin, brain/nervous system, and kidneys, and a predisposition to tumors. The diseases are named after a characteristic abnormal growth in the brain, which takes the shape of a tuber or root.
Causes, incidence, and risk factors
Tuberous sclerosis is inherited as an autosomal dominant trait (only one parent must pass on the bad gene for the child to get the disease). However, a high percentage of cases are due to new mutations (which occur in the sperm or egg of one of the parents), so there usually is no family history of the disease.
It is one of a group of diseases described as neuro-cutaneous syndromes because of extensive involvement of both the skin and the central nervous system (brain and/or spinal cord).
The symptoms of tuberous sclerosis vary considerably: from minimally affected people with normal intelligence and no seizures to severely affected people with profound retardation and frequent, difficult-to-control seizures or serious tumors.
Severely affected people may develop seizures shortly after birth. These are characterized by infantile spasms (hypsarrhythmia). Mental retardation becomes evident as infants begin to miss their normal developmental milestones.
Infants may have heart tumors (rhabdomyoma), which can be detected by ultrasound. These tumors may grow or shrink and usually do not cause problems.
Several different skin lesions are common in tuberous sclerosis.
- “Ash leaves” are depigmented or hypopigmented (lacking normal skin color) white lesions that have the shape or appearance of an ash leaf and may appear anywhere on the body.
- Shagreen patches: These appear on the lower back as raised patches of skin with an orange-peel texture.
- Adenoma sebaceum (angiofibroma): These lesions include red, highly vascular lumps on the face that may resemble irritated acne. These enlarge with age and may run together (become confluent) to form larger patches.
The incidence is approximately 1 in 25,000-30,000 births. There are no known risk factors other than having a parent with tuberous sclerosis. In that case, each child has a 50% chance of inheriting the disease.
- Ash leaf spots of skin, and less often, cafe-au-lait spots
- Shagreen spots of the skin, if present, likely on the back
- Red, highly vascular lumps on the face (adenoma sebaceum)
- Mental retardation
- Rough growths under or around fingernails and toenails
- Pitted dental enamel
- Kidney tumors
Signs and tests
- Examination of the eyes may show retinal abnormalities, pale patches, mulberry tumor or phakoma or astrocytoma (tumor).
- There may be some indications of heart abnormalities including abnormal heart rhythm (electorcardiogram) or tumor (rhabdomyoma) on ultrasound.
- An MRI of the head demonstrates tumors or benign “tubers” in the brain.
- A CAT scan of the head may reveal calcium deposits in the brain.
- The mouth may show rubbery growths in tongue or gingiva.
- Ultrasound of kidney may show cysts, fatty benign tumors or serious tumors.
- Ultraviolet light examination of the skin may show ash leaf spots not visible in ordinary light.
- There may be a family history of the condition. Genetic testing for either of two genes that can cause this disease (TSC1 or 2) may be available.
There is no specific treatment for tuberous sclerosis. Treatment is tailored to the symptoms. Medications are required for controlling seizures, which is often difficult. Special schooling or care is determined by the severity of mental retardation.
Adenoma sebaceum (small growths) on the face may be removed by laser treatment. These lesions tend to recur and repeat treatments will be necessary.
Heart tumors called rhabdomyomas commonly disappear after puberty so surgery is usually not necessary. Regular ultrasound of kidneys is important screening for adults to make that sure tumors do not grow.
For additional information and resources, contact the Tuberous Sclerosis Alliance at 800-225-6872.
Children with mild tuberous sclerosis usually do well. Occasionally, a severely affected child will be born, the parents are examined, and one of them is found to have had a mild case of tuberous sclerosis that escaped detection.
Children with profound retardation or uncontrollable seizures usually do poorly. Although numerous benign tumors occur in this disease, some, such as renal or brain tumors, can become malignant.
- severe mental retardation
- brain tumors (astrocytoma)
- uncontrollable seizures
- rhabdomyoma of the heart
Calling your health care provider
Notify your health care provider if either side of the family has a history of tuberous sclerosis. Since tuberous sclerosis also appears as a spontaneous mutation, call your health care provider if you notice symptoms suggestive of tuberous sclerosis in your child. Call a geneticist if your child is diagnosed with cardiac rhabdomyoma, as tuberous sclerosis is the leading cause of this tumor.
Genetic counseling is recommended for prospective parents with a family history of tuberous sclerosis. Prenatal diagnosis may be available for families with a known DNA mutation. Tuberous sclerosis frequently appears as a new mutation; these cases are not preventable.
by Mamikon Bozoyan, M.D.