Tuberous sclerosis

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at November 1, 2016
StartDiseasesTuberous sclerosis

Tuberous sclerosis, also known as tuberous sclerosis complex (TSC), is a type of genetic disorder. It belongs to a group of diseases and disorders known as subcutaneous syndromes, meaning that in addition to the skin, TSC also involves the central nervous system. This disorder leads to the growth of benign (non-cancerous) tumors in various areas of the body. The tumors grow to resemble roots within a tube-like shape, contributing to the disorder's name. Symptoms of TSC can be mild and minimal, or more pronounced and numerous. Each patient's experience will be different because it does occur on a cellular level and every person's cells are different. Synonyms include Bourneville's disease and epiloia.

Contents

Definition & Facts

TSC affects specific genes, the TSC1 gene and TSC2 gene. The disorder causes a mutation in these two genes. TSC1 is a gene that produces a protein called hamartin, while TSC2 produces another protein called tuberin. Together, these two proteins work to regulate the growth and size of cells.

Cells will grow in abnormal shapes or in mass quantities, consistently replicating the mutation with each cell. This abnormal cell growth contributes to the growth of tumors. Organs are affected as the cells of each organ change from the mutation of the TSC genes. For example, mutation in the kidney cells will result in tumor growth in the kidney.

  • On average, between 25,000 and 40,000 Americans are affected by TSC.
  • One out of every 6,000 newborns are born with TSC worldwide
  • Discovered over 100 years ago by a French doctor.

Symptoms & Complaints

Symptoms experienced can vary greatly from one individual to another, and depending on what areas of the body are affected. Benign tumors are one of the common symptoms of tuberous sclerosis. Patients with TSC involving the brain may experience seizures, sleep troubles, nausea, and headaches. Other common symptoms include changes in the skin, difficulties with organ functions, and developmental delays.

Cardiac tumors, called rhabdomyomas, are common tumors found in both prenatal ultrasounds and in small children with TSC. Research has shown that these tumors are often the largest in size by birth. If tumors are shown to be abnormally large or there are multiple tumors present, circulation of the blood can suffer. At this point, removal is often immediate. If tumors have not increased in size by birth, they tend to shrink as the child grows. Many doctors, however, choose to remove the tumors before they have the ability to cause trouble.

Problems with the skin are another common symptom of TSC. Many skin abnormalities that occur are not problematic and tend to be more cosmetic in nature. These abnormalities include the appearance of white patches called leaf spots and reddened areas that closely resemble acne. Most changes in the skin will resolve without medical intervention. While they can be bothersome, the occurrence of these skin abnormalities can actually help doctors diagnose TSC.

Causes

Tuberous sclerosis will either be inherited, sporadic, or due to gonadal mosaicism. Inherited cases stem from one parent passing the gene to the affected child, known as autosomal dominant disorder. When one parent has the disorder, children have a 50% chance of developing tuberous sclerosis, and with different symptoms than the parent may have.

Finally, TSC can be due to germline mosaicism, although this is rare. Genetic mutations or defective genes cannot be found in the parents. Instead, a genetic mutation is found only in the reproductive cells of a parent, without involving any other cells. Genetic testing involving only the blood does not show evidence of this rare occurrence. If gonadal mosaicism is suspected, samples of the parent's reproductive material can be analyzed to locate a mutation.

If neither parent suffers from the disorder or has a faulty TSC1 or TSC2 gene, and gonadal mosaicism has been ruled out, a case of TSC in offspring is considered sporadic. This means that the affected person has the first mutation of one or both genes. He or she can then pass this new mutation to his or her offspring.

Diagnosis & Tests

In diagnosis an affected person, one of the first ways doctors begin to suspect TSC is through the occurrence of development issues or seizure activity. Identification of physical symptoms, such as tumors and skin changes, also aids in initial diagnosis. When doctors suspect TSC, numerous tests are performed to confirm diagnosis.

CT scans and magnetic resonance imaging scans may be used to determine if tumors are present. Ultrasounds of organs are used to see if tumors are growing in other organs. Genetic testing on the affected individual and both parents can show defect or mutation of the TSC genes.

Treatment & Therapy

TSC itself cannot be cured because the genes are permanently mutated. There are, however, treatments used for many of the symptoms that can be experienced. Seizure medications can be prescribed to control seizure activity. Tumors can be treated, or surgically removed when necessary, to reduce organ troubles. Behavioral issues may also require the use of medications.

Children with TSC may often require educational intervention. Occupational therapy can be used to aid with developmental delays. Oxygen therapy and light therapy can be beneficial in treating respiratory and skin issues, respectively. Cognitive behavioral therapy can aid in addressing and correcting behavioral issues.

Prevention & Prophylaxis

Due to how TSC works, prevention of the disorder is not possible. When parents have a history of TSC, genetic counseling is often recommended. Management of symptoms helps prevent symptoms from making the condition worse. Early detection is pertinent in reducing the appearance and severity of symptoms.

Tumors must be closely watched. Because they are benign in nature, they do not respond to the same treatments as cancerous tumors. As such, tumors are usually removed as early as possible to avoid potential complications. Certain inhibiting medications approved by the FDA, such as mTOR inhibitors, can help reduce the risk of developing life-threatening tumors, including tumors of the brain.