Introduction
Tuberous sclerosis is a complex genetic disorder (a disease that occurs due to some defect in the genes) that is characterized by skin lesions, nervous system affectation, and renal involvement primarily. The name is derived from tuber-like growths on the brain that become hard. These tubers are seen as white areas on a CT Scan of the brain. These abnormal growths can affect any organ of the body (even the eyes, kidneys, heart, and lungs).
Every individual with tuberous sclerosis is affected differently. Some individuals are totally unaffected whereas some people are more severely affected.
How Common is Tuberous Sclerosis?
Out of every 6000 newborns, one may have tuberous sclerosis. More than 1 million people around the world are known to have tuberous sclerosis. These may still be many undiagnosed cases and mild forms of the disease.
Why Does Tuberous Sclerosis Occur?
Tuberous sclerosis is a genetic disorder (due to errors in the genes). Children have a 50% chance of inheriting tuberous sclerosis if one of the parents has this condition. However, 2/3rd of the cases are due to spontaneous genetic errors, the cause of which is still a mystery.
Why does Tuberous Sclerosis affect so many Body Organs?
In tuberous sclerosis, there is a growth of normal body tissue in a disorganized way (hamartomas). They interfere with the functioning of the organ in which they are growing. When the person becomes an adult, the growth of the organ and the hamartoma stops. As a result, most patients have a normal life span. However, there may be occasional serious problems (kidney, lung, or brain tumors) that need to be dealt with later in life.
Presentation
The disease spectrum of tuberous sclerosis is very diverse. Some may present with a very severe form whereas some may be totally unaffected.
Tuberous sclerosis primarily affects the brain, skin, eyes, kidneys, heart, and bones.
Brain
: Due to the growth of tuber-like structures, these patients may have fits (convulsions), mental retardation, behavioral problems, and learning disability. Infants may develop a peculiar kind of fit called salaam fits (infantile spasms). These fits appear as if they are bowing down in a salute. As the child grows the fits may change or sometimes just stop altogether.
Learning disabilities are also quite common. By the age of 2 years, it is quite clear whether a child with tuberous sclerosis will have developmental problems or not.
Tubers may block the flow of the brain fluid (CSF) causing retention of fluid in the brain (hydrocephalus). It may present as headache, vomiting, walking problems, and worsening of fits.
Skin
: The earliest sign to develop would be white skin patches (ash-leaf patches) especially on the limbs and the trunk. They cause no problems and disappear later in life. As the child grows older, a characteristic facial rash known as adenoma sebaceum (facial angiofibroma) develops across the nose and the cheeks. At first, the rash starts as pinpoint spots which later form small bumps. Later in life, small nodules of skin form around the fingers or toenails (Periungual Fibroma). Shagreen patches appear on the lower back as raised patches of skin with an orange-peel texture.
Kidneys
: Kidney disorders are seen in 40 - 80 percent of patients with Tuberous sclerosis. They usually cause problems in the 2nd and 3rd decades of life. Tumors of the kidney (angiomyolipoma) and cysts are the most common lesions seen. These may cause bleeding from the kidney either into the urine, around the kidney or in the abdomen. There may be abdominal pain, fever, anemia (low hemoglobin), and general illness. Kidney failure is rare. Hence, regular monitoring of kidney problems with kidney ultrasound (1 to 3 yearly), urine, and blood tests with blood pressure monitoring is necessary. Polycystic kidney disease may also be seen. It causes high blood pressure and deteriorating kidney function. There are so many cysts that compress the normal kidney and ultimately deteriorate renal functions. Hence regular monitoring is required.
Heart
: There are benign rare growths in the heart known as rhabdomyomas. They tend to progressively grow smaller and disappear after the first year of life. A child with tuberous sclerosis may develop heart failure, which may present itself as shortness of breath, fainting spells (not due to fits), and swelling of ankles.
Eyes
: It causes growth in the retina of the eye called retinal hamartoma or phacoma.
Diagnostic Criteria
Table 1. Diagnostic criteria for Tuberous sclerosis
| Primary features (Only one feature is required to make a diagnosis) |
Secondary features (Two or more features are required to make a diagnosis) |
- Classical Shagreen patches.
- Ungual fibroma
- Retinal hamartoma
- Facial angiofibroma
- Subependymal glial nodules
- Renal angiomyolipoma
|
- Hypomelanotic macules
- Gingival fibromas
- Bilateral polycystic kidneys
- Cardiac rhabdomyoma
- Cortical tuber (histological)
- Radiographic 'honeycomb' lungs
- Infantile spasms
- Myoclonic, tonic or atonic seizures
- First degree relative with tuberous sclerosis
- Forehead fibrous plaque
- Giant cell astrocytoma
|
Reference: Tuberous sclerosis Medical Booklet, modified from Gomez
Antenatal Diagnosis
In 2/3rd of the cases, tuberous sclerosis is a spontaneous mutation, and no one else in the family is affected. There are no definitive tests to diagnose tuberous sclerosis in the unborn. Sometimes echocardiography of the baby's heart during mid-pregnancy may provide evidence of lesions but gives no indication of how severely the baby is affected.
Diagnosis
Since the effects of Tuberous sclerosis are variable, the condition can be diagnosed anytime from infancy to adulthood. By the age of 5 - 10 yrs, it is possible to predict the extent of the disease and problems that can occur later.
A classical picture of Tuberous sclerosis is mental retardation, epilepsy, and adenoma sebaceum. Depending upon the age of the child, the following tests are done:
- Brain MRI or CT Scan
- EEG
- Skin examination under UV light (Wood's Lamp)
- Echocardiogram of the heart
- Ultrasound of the kidneys
- Eye examination
- Blood test to check renal functioning and anemia
Management
Unfortunately, there is no cure for tuberous sclerosis but treatment is available for various related symptoms.
For a child below 5 years:
Epilepsy: It may not always be possible to stop fits altogether, however, the best possible control with minimum side effects should be the goal. Infantile spasms can be well controlled with Vigabatrin.
Developmental delay: The speech and communication are usually delayed rather than motor delay.
Sleep problems: Blood pressure and a blood test for renal functions should be checked annually.
For children between 5-10 years:
Standard eye and hearing check-ups should be carried out. These are especially important in a child with a learning disability so that these problems can be corrected to maximize the learning capacity. A regular dental checkup is also important as certain anti-epileptic medication may cause teeth problems.
For children above 10 years:
Kidney problems should be monitored as they may turn up later. Facial rash (adenoma sebaceum) may be seen and can be disguised with special make-up or treated with laser therapy. Signs for hydrocephalus should always be looked for.
Prognosis
Most people affected by tuberous sclerosis have a normal life span. Over 50% of people with tuberous sclerosis are intellectually normal. The remainder have learning disabilities to a greater or lesser extent.