Tuberous Sclerosis
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- Last Updated on 14 December 2016
Tuberous sclerosis, often referred to as tuberous sclerosis complex (TSC), is a relatively common cause of infantile spasms. TSC is termed a neurocutaneous disorder because it usually affects both the skin and brain, as well as multiple other organs. Skin involvement typically includes birthmarks which are white, flat, and oval in shape (Ash-leaf spots), rough patches of skin most frequently seen over the lower back (Shagreen patch), and acne-like growths on the face (angiofibromas, formerly termed "adenoma sebaceum"). Brain findings include cortical tubers (abnormal brain tissue that often leads to seizures and infantile spasms), subependymal nodules (a characteristic growth which often protrudes into the fluid-filled spaces within the brain--ventricles), and subependymal giant-cell astrocytomas (abbreviated SEGA, which can be a cause of hydrocephalus, a condition in which fluid movement in the brain is obstructed, leading to abnormal enlargement of the skull, headaches, and other problems). Other affected organs include the heart (rhabdomyomas, which are tumors that often disappear with age but which can occasionally lead to abnormal heart rhythms), the lungs (spontaneous pneumothorax, which is a perforation of the lung caused by an abnormal growth called lymphangioleiomyomatosis), and the kidneys (cysts as well as angiomyolipomas, which are a type of tumor that is usually benign but sometimes leads to blood in the urine). Most patients with TSC do not have all of the above findings, but usually some combination thereof. At the age when infantile spasms is typically observed, the most common findings include Ash-leaf spots and cortical tubers.
TSC is a genetic disorder in which the vast majority of cases are caused by a mutation (abnormal DNA sequence) in one of two genes, called TSC1 and TSC2. These genes are important for regulating growth and proliferation of multiple body tissues. As such, when one of these genes is dysfunctional, abnormal proliferation of specific tissues leads to the symptoms and findings mentioned above.
The diagnosis can be established "clinically" by observing the aforementioned symptoms/findings, and definitively confirmed and characterized by gene-testing, i.e. sequencing of the TSC1 and TSC2 genes. Most people with TSC have sporadic mutations, meaning that the condition is caused by a new mutation and not inherited by either parent. However, in approximately one-third of cases, TSC is inherited from an affected parent. The inheritance pattern is described as "autosomal dominant" meaning that children of an affected parent have a 50% chance of developing TSC.
With regard to treatment, TSC is rather unique in that the diagnosis clearly impacts treatment decisions. It appears that the effectiveness of vigabatrin (Sabril®) is superior among patients with TSC in comparison to patients with other causes of infantile spasms. As such, vigabatrin is usually the treatment of choice among children with TSC. There is also ongoing scientific inquiry to determine whether the use of vigabatrin could help prevent the development of infantile spasms in children diagnosed with tuberous sclerosis at birth.
In addition to vigabatrin, another class of drugs including sirolimus/rapamycin (Rapamune®) and everolimus (Afinitor®) have been used to treat subependymal giant-cell astrocytomas and skin symptoms, but have not been sufficiently evaluated for treatment of infantile spasms.
For additional information and support, please visit the Tuberous Sclerosis Alliance.
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