Mutations in TSC1 cause a condition called Tuberous Sclerosis.
People with this condition may have many benign tumors as well as epilepsy (80-90% of individuals), cognitive disability, and/or autism spectrum disorder. Most individuals with the mutation develop benign brain tumors. However, these do have some potential to become cancerous. Additionally, 70-80% of affected individuals also develop benign tumors in the kidneys which again, have a 2-5% chance of becoming cancerous. These tumors are also seen in the eye of about 50% of patients. In most cases, this does not affect vision. In women with mutations in TSC1, about 80% develop cystic lung disease by the age of 40. Additionally, many women develop lymphangioleiomyomatosis, or LAM. In many individuals, this condition is asymptomatic. The majority of newborns with this mutation will have an irregular heartbeat, which is usually detected in prenatal ultrasound. However, this problem often fixes itself over time. Many affected individuals will have marks or spots on their skin however, this is not cause for concern.
It is recommended that individuals with a TSC1 mutation receive and brain MRI every 1-3 years, even in asymptomatic patients. Affected individuals should also receive a baseline EEG as well as an EEG after any epileptic episode. Additionally, cognitive testing should be completed annually. In order to screen for potential complications with the kidney, patients should have an annual blood pressure measurement, evaluation of renal function, and an MRI of the abdomen every 1-3 years. Individuals should also receive an annual eye and dermatologic examination. As for the lungs, females should receive a baseline pulmonary function test before the age of 18 and repeat the test every 5-10 years. It is also important to educate young females of the effects of smoking and estrogen exposure to their health. Lastly, screening for the heart includes a baseline Echocardiogram before the age of three, which should then be repeated every 1-3 years. In asymptomatic patients, an ECG should be performed every 3-5 years.
Mutations in TSC1 are inherited in an autosomal dominant manner, meaning each first degree relative (parent, child, and sibling) of an individual with this condition has a 50% chance of inheriting the disease causing mutation.