Tuberous Sclerosis Complex

Tuberous sclerosis complex (TSC) is a genetic disorder with the growth of non-cancerous tumor involved in many parts of the body. Tumors can devleop in various organs, including the brain, eyes, heart, kidneys, skin, and lungs. Symptoms related to tubeorus sclerosis complex (such as seizures, developmental delays, intellectual disabilities, and autism) particulary affects the quality of life for patients and their families. The clinical features and severity of this disease vary widely among patients, and many individuals with tuberous sclerosis complex live independently. The incidnece of this disease is about 1 in every 6,000 people, with an estimated total of around 1 million patients worldwide. 

Tuberous sclerosis complex is a multisystem genetic disorders that causes benign tumors and other abnormalities in various organs. Clinical features vary widely among individuals, even within the same family. 

Neurology

Structural abnormalities in the brain are commonly observed, including multiple cortical tubers in the cerebral cortex, subependymal nodules near the ventricles, and subependymal giant cell astrocytomas, which are a type of brain non-malignant tumor. Seizures are the most common neurological symptom, occurring in approximately 85% of all patients. In tuberous sclerosis complex, seizures commonly begin in early childhood, with the majority of patients experiencing seizures within the first year of life. About one-third of these cases present as infantile spasms. The types of seizures seen in patients with tuberous sclerosis complex are highly variable. Tuberous sclerosis complex is closed associated with a wide range of cognitive, behavioral, and psychiatric symptoms, such as intellectual disability, autistic spectrum disorder, attention deficit, and hyperactivity disorder.

Eyes

Medical issues related eyes are observed in about half of patients with tuberous sclerosis complex. Although vision loss is uncommon, retinal hamartomas and depigmented patch, which typically do not require treatment, may be observed. 

Kidneys

Small cysts, anigomyolipomas, and renal cancer can develop in the kidneys, and over 80% of individuals with tuberous sclerosis complex will experience at least one type of kidney disease during their lifetime.

Skin

Most individuals with tuberous sclerosis complex develop skin changes. Characteristic lesions that help with diagnosis include light-colored hypopigmented macules, angiofibromas, forehead plaques, periungal fibromas (around the nails), and shagreen patches on the back. Some of these skin findings are present from birth, while others may first appear during adolescence or adulthood. Many of these lesions can be effectively managed through surgical treatment or newer medications that have recently been developed.

Lung

Lymphangioleiomyomatosis is a lung disease that commonly occurs in women of reproductive age. It is characterized by the abnormal proliferation of smooth muscle-like cells invading the lungs, airways, blood vessels, and lymphatic vessels. This abnormal growth alters the structure of the lungs and interferes with the respiratory function.

Heart

The most common cardiac finding in patients with tuberous sclerosis complex is rhabdomyomas (benign heart tumors). In about 50% of patients, rhabdomyomas are found, and the symptoms vary depending on the location, number, and size of the tumors. Som patients are also diagnosed with vascular conditions such as coarctation of the aorta, renal artery stenosis, or thoracic or abdominal aortic aneurysms. 

Others

Cyst or angiomyolipomas can be found in organs such as the adrenal glands, liver, lungs, ovaries, and pancreas. These lesions are typically asymptomatic and do not require treatment.

To date, two genes, TSC1 and TSC2, have been identified as the causative genes of tuberous sclerosis complex. The TSC1 gene is located on chromosome 9 and produces a protein called hamartin, while the TSC2 gene is located on chromosome 16 and produces a protein called tuberin. Hamartin and tuberin function together by forming complex, so mutations in either gene can cause the same disease, tuberous sclerosis complex. When the function of hamartin or tuberin is impaired, benign tumors called hamartomas can develop.