Tuberous Sclerosis

Children diagnosed with tuberous sclerosis share three common findings: small bumps on the skin of the nose and face called sebaceous adenomas, uncontrolled epilepsy and developmental delay. Noncancerous tumors such as subependymal nodules (SENs) and subependymal giant cell astrocytomas (SEGAs) may occur in the brain, in addition to other growths called cortical tubers. These growths may cause problems with normal brain function.

Tuberous sclerosis is part of a group of multisystem disorders that involve the central nervous system. Related conditions include:

• Neurofibromatosis (NF1 and NF2)
• Sturge-Weber syndrome
• Von Hippel-Lindau syndrome

Tuberous sclerosis is a genetic condition. Mutations on two genes (TSC1 and TSC2) on chromosomes 9 and 16, respectively, cause the condition. The disorder is autosomal dominant, meaning only one of the two gene mutations needs to be present for tuberous sclerosis to occur. A child has a 50 percent chance of inheriting the condition if one parent also has tuberous sclerosis. Tuberous sclerosis rarely develops through spontaneous genetic mutations.

The symptoms of tuberous sclerosis vary depending on the organs and body systems affected:

• Central nervous system symptoms
  • Seizures. Most patients with tuberous sclerosis have seizures early in life. Seizures can be difficult to control with medicine alone, and surgical treatment may be needed.
  • Developmental delay. Between one-half and two-thirds of patients experience developmental delay, ranging from learning disabilities to debilitating impairment.
• Heart symptoms
  • Cardiac rhabdomyomas. Rhabdomyomas are benign tumors of striated muscle. They may develop in young patients. If rhabdomyomas are large enough, they may disrupt the circulation of blood and cause sudden death from heart failure.
• Lung symptoms
  • Lung lesions. There are two kinds of lung lesions caused by tuberous sclerosis: lympangioleiomyomatosis (LAM) and multinodular multifocal pneumocyte hyperplasia (MMPH). Most lung lesions are asymptomatic, but in a minority of cases, patients may present with shortness of breath.
• Kidney symptoms
  • Angiomyolipomas. Angiomyolipomas are benign growths on the kidneys that cause no symptoms in most cases. Rarely, tumor growth and large size may cause bleeding and acute kidney injury.
  • Renal cell carcinoma. Renal cell carcinoma is a less common malignant (cancerous) kidney tumor present in tuberous sclerosis.
  • Oncocytomas. Oncocytomas are tumors of epithelial cells with too many mitochondria. While often noncancerous, oncocytomas can be premalignant or malignant.
• Eye symptoms 
  • Retinal phakomas. Phakomas are noncancerous growths on the retina. They usually do not cause symptoms, but their presence is associated with a diagnosis of tuberous sclerosis.
• Skin symptoms. In addition to sebaceous adenomas, other skin lesions include:
  • Ash leaf spots. White or light patches of the skin.
  • Shagreen patches. Leathery, pebbly skin on the nape of the neck.
  • Ungual or subungual fibromas. Tumors that grow under the toenails or fingernails.
  • Skin tags. Small flaps of skin that form on the skin’s surface.

With early treatment and monitoring, life expectancy for children with tuberous sclerosis is usually good. Lifelong monitoring is necessary to watch for any possible negative effects of tumors in the central nervous system and other organ systems.

Diagnosis of Tuberous Sclerosis

Doctors at Riley at IU Health first examine your child for the three common findings of tuberous sclerosis: sebaceous adenomas, intractable epilepsy and developmental delay. Other diagnostic tests include:

• Computed tomography (CT) scan. This X-ray scan combines cross-sectional images to create detailed pictures of the brain and to look for cortical tubers, SENs or SEGAs.
• Magnetic resonance imaging (MRI). MRI uses radio waves and a magnetic field to create computer pictures of the brain and check for the presence of any cortical tubers, SENs or SEGAs.
• Ultrasound. Ultrasound imaging uses sound waves to create pictures of the heart and kidneys to screen for mass lesions.
• Neurosurgery referral. If your child shows brain abnormalities or has seizures that cannot be controlled by medicine, his or her neurologist may set up an appointment with an epileptologist and a neurosurgeon.