The symptoms of tuberous sclerosis complex (TSC) can be extremely variable, with some patients experiencing no significant problems at all, and others having serious, life-threatening complications. The diagnosis of TSC generally requires evidence of at least two of the major types of typical tumors or lesions characteristic of this disease.
TSC symptoms include:
Neurological symptoms are common among many people with TSC and may include epilepsy, learning disabilities, developmental delays and behavioral problems and/or autism.
Epilepsy is very common in TSC, with some studies estimating that ~80-90% of patients with TSC will develop seizures. The seizures themselves can vary in their features, ranging from the dramatic convulsion (generalized tonic-clonic seizure) to the more subtle staring spell (absence or complex partial seizure).
Infants with TSC often develop a special type of seizure, called infantile spasms, usually involving repetitive clusters of spasm-like or startle-like movements.
While the epilepsy in some patients with TSC can be controlled with medication, unfortunately many patients with TSC have poorly-controlled seizures.
While many patients with TSC have normal intelligence, TSC patients are also at risk for cognitive or learning problems, perhaps occurring in about 50% of patients and ranging from mild learning disabilities and attention problems to severe mental retardation, as well as delays in motor skills.
Behavioral problems and autism represent another disabling neurological manifestation that can occur in a significant proportion of patients with TSC.
Growths in the brain
The neurological manifestations of TSC may be related to various abnormal lesions or growths in the brain including tubers, subependymal nodules (SENs) and subependymal giant cell astrocytomas (SEGAs).
Tubers are small, discrete areas in the brain, especially the outer region called the cortex, where the brain did not develop normally. Although the terminology can be confusing, tubers tend not to grow like tumors typically do; however, it is believed that the disruption of the normal brain by tubers most likely causes the seizures, and possibly contributes to the cognitive problems and autism in patients with TSC.
Subependymal nodules (SENs) are small bumps lining the spinal fluid-filled spaces (ventricles) towards the middle of the brain. SENs are not thought to directly cause any neurological symptoms. However, some patients with TSC develop subependymal giant cell astrocytomas (SEGAs), which can grow like a typical tumor. When growth of SEGAs obstructs the flow of spinal fluid through the ventricles, this can sometimes lead to a more emergent situation due to pressure build-up in the brain, often presenting with progressive lethargy, behavioral changes, headache, or vomiting.
Skin involvement is common as a more obvious symptom of TSC. Changes to the skin may include hypopigmented macules, Shagreen patches, facial angiofibromas and periungual fibromas.
Hypopigmented macules are light-colored (lighter than the patient’s normal skin color), flat spots on the skin, that sometimes have a classic “ash-leaf” shape. In some patients with TSC, these light spots are so subtle that it takes a special ultraviolet light (Wood’s lamp) to detect them.
More obvious in appearance, Shagreen patches are raised, rough lesions, resembling an orange peel, often found on the lower back.
Facial angiofibromas are small, often red-colored, bumps that typically occur over the bridge of the nose and cheeks on the face. These often do not develop until later in childhood, but can eventually become quite extensive and bothersome.
Periungual fibromas refer to small growths along the finger and toe nails.
While most tumors in TSC usually do not spread (metastasize), behave aggressively, or become cancerous, tumor growth can still sometimes cause serious symptoms and involve organs such as the heart, kidney, lung and eye.
In many cases, the heart involvement does not cause significant symptoms and the heart tumors, called cardiac rhabdomyomas, tend to resolve with age.
Heart involvement, when significant, usually affects infants and can cause abnormal heart rhythms (arrhythmias) or symptoms of heart failure.
Kidney involvement is usually minimal and asymptomatic in infants and children. As patients with TSC get older, growth of kidney tumors called renal angiomyolipomas can start to cause problems with hypertension and bleeding, and rarely can become cancerous.
Lung involvement is almost never significant until adulthood, and strangely, primarily affects women with TSC, who develop a disease known as lymphangioleiomyomatosis. If this lung involvement progresses, there can be significant compromise of respiratory function, sometimes even requiring lung transplantation.
Tiny tumors can occur in the back of the eye, or retina, called retinal hamartomas, but fortunately these do not cause significant visual impairment in most cases.