Signs & Symptoms of TSC

Signs and symptoms of tuberous sclerosis complex (TSC)

Because TSC affects no two people the same, there is no sure way to predict where and how the disorder will manifest. To better understand its potential impact, click below on the organs most often targeted.

Brain Involvement

Several types of brain lesions are seen in individuals with Tuberous Sclerosis Complex (TSC); some people will have all the lesions, whereas others will have no brain involvement at all.

Cortical tubers (from which TSC is named) can be thought of as a “birth defect” on the brain. They are small areas in the cortex (the outer layer of the brain) that do not develop normally. It is thought that the presence of cortical tubers, which disrupts the normal “wiring” of the brain, is what causes seizures in individuals with TSC.

Subependymal nodules develop near the walls of the cerebral ventricles (the cavities in the brain that contain cerebrospinal fluid).

Typically, these nodules accumulate calcium within the first few months or years of life. Because of this calcification, they can be easily detected with a computed tomography (CT) scan. The subependymal nodules are not directly responsible for neurological problems.

Subependymal giant cell astrocytomas (SEGAs). This type of tumor develops in approximately 15 percent of individuals with tuberous sclerosis. Typically, SEGAs do not occur in very young children, and the chance for their growth decreases after age 20.

If a giant cell astrocytoma grows large enough, it can block the flow of fluid inside the ventricles of the brain, and the tumor will have to be removed and/or the ventricles shunted to relieve fluid buildup and pressure. Symptoms include vomiting, nausea, and headaches as well as changes in appetite, behavior, and mood. These symptoms may or may not signal growth of a tumor, but they do signify that there may be a problem and that the child should be seen by a physician.

Brain imaging should be done at the time of diagnosis to get a baseline image and then every 1 to 3 years afterward. A brain scan can sometimes show growth of a tumor even before symptoms develop.

The most common affect of brain manifestation is epilepsy or seizures. Seizures occur in approximately 85 percent of individuals diagnosed with TSC.

Skin Involvement

Individuals with Tuberous Sclerosis Complex (TSC) often see the disease manifested in the skin, including on the face, body and nails. In some cases, skin growths can become obtrusive but in most cases, the growths themselves are harmless. However manifestations such as facial angiofibromas can have a social impact and treatments are available.

Skin lesions resulting from TSC include:

  • hypomelanotic macules—patches of skin lighter than the surrounding skin (can be any size or shape or may be the classic “ash-leaf” shape)
  • shagreen patch—a patch of skin that is tough and dimpled like an orange peel
  • periungual or subungual fibromas—fibrous growths that appear around the fingernails and toenails;
  • facial angiofibromas—tumours of the face. Fibrous plaques sometimes appear on the forehead of individuals with TSC. There may also be fibrous, hairless scalp plaques surrounded by thin, white tufts of hair.

At the initial testing, the doctor uses a Wood’s lamp (an ultraviolet light) to better visualise the hypomelanotic macules—white patches on the skin that often are difficult to see, especially on infants and people with very pale skin. The entire body should be examined. The skin should be carefully examined for the other skin manifestations of TSC as well.[/cs_text][cs_text class=”mtm”]Some of the skin signs may not be present at birth; the facial angiofibromas do not usually appear until between the ages of 3 and 5 at the earliest, and the periungual and subungual fibromas do not usually occur until much later in life. Lesions that appear later should be noted and brought to the attention of the doctor.

The most often treated skin manifestations of tuberous sclerosis complex (TSC) are the facial angiofibromas and periungual and subungual fibromas. The facial angiofibromas can be treated with Rapamycin (Sirolimus) cream or by laser surgery.


Individuals with TSC are more susceptible to sunburn and should be careful about sun exposure and use a broad-spectrum sunscreen.  These sunscreens protect against UVA and UVB and should have a sun protection factor (SPF) of at least 30.  Sunscreen should be applied to all areas exposed to the sun, since tanning of surrounding skin will make the hypomelanotic macules more apparent.

Lung Involvement

The main lung lesion found in TSC is lymphangioleiomyomatosis (LAM). LAM occurs almost exclusively in women and in TSC. Some studies estimated that LAM will occur in 80% of women with TSC. Lung involvement in tuberous sclerosis complex (TSC) has been identified for many years. In 2000-2001, three studies reported that between 26% and 39% of women with a diagnosis of TSC have lymphangioleiomyomatosis (LAM) (Costello et al., 2000; Franz et al., 2001; Moss et al., 2001).  Several subsequent studies suggested that the frequency of lung involvement in adult women with TSC may be higher than previously suspected, ranging from 42% to 49% (Muzykewicz et al, 2009; Adriaensen et al, 2011; Cudzilo et al., 2013). Fortunately in many of these women, the disease does not cause significant respiratory symptoms. Due to the frequency of lung involvement in TSC, the recent TSC Consensus Conference report recommended that all women age 18 years and older with TSC should have a computerised tomography (CT) scan of the chest and pulmonary function testing. (Krueger et al., 2013).

The first symptoms of lung involvement in an individual with TSC may be shortness of breath after mild exercise, spontaneous coughing. Progression to lung failure may develop, but not usually until the third or fourth decade of life, if at all. Lung involvement in TSC can be severe, and some individuals will require lung transplantation.

If pulmonary involvement is noted, the individual should be monitored closely and should have repeated chest scans as needed.

Kidney Involvement

The majority of individuals (greater than 80%) with tuberous sclerosis complex (TSC) will develop some form of renal (kidney) disease during their lifetime. There are three main renal disorders in TSC:  renal cysts, renal angiomyolipoma and renal cell carcinoma.

Renal angiomyolipomas, are usually the greatest concern in TSC. The blood vessels within angiomyolipomas are abnormal and can develop weak spots in their wall, called aneurysms, that can burst and lead to bleeding. Renal angiomyolipomata occur in approximately 80% of TSC patients.  Most of the time both kidneys are involved.

Renal cysts are often small, benign fluid filled “holes” in the kidney that occur in about 50 percent of individuals with TSC.  These cysts, though not common, can lead to elevated blood pressure, but usually do not cause discomfort.  Sometimes the kidney is filled with cysts, and this can lead to kidney impairment and even kidney failure, requiring dialysis or transplantation.

Renal cell carcinoma (cancerous tumours of the kidney), although rare in TSC, must be kept in mind.

The current methods used to diagnose these renal abnormalities include renal ultrasonography, CT scanning and magnetic resonance imaging (MRI). These are all non-invasive procedures that are available in almost every major hospital. The renal ultrasound provides the least detailed image of the kidney, while the MRI provides the most detailed. In general, the ultrasound is sufficient to detect both renal cysts and fat-containing angiomyolipomas, but may not provide enough detail to accurately measure and follow the renal lesions and can miss lesions that lack the fat component.

The kidneys should be scanned, preferably with MRI, at the time of diagnosis, and at 2-3 year intervals if no cysts or angiomyolipomas are identified. If kidney lesions are identified, then the growth of these lesions should be followed using repeated MRI every year or two, unless symptoms develop or the lesion has an unusual growth pattern. Imaging is critical to assess if kidney lesions are present and/or if there has been a change in any of the existing kidney lesions.

Renal angiomyolipomas—made up of vascular tissue (angio), smooth muscle (myo), and fat (lipoma)—are benign hamartomas. These hamartomas are well circumscribed groups of cells that multiply excessively, growing as tumours that may or may not cause symptoms. The prevalence of TSC-related renal angiomyolipomas increases with age, and in adults bilateral tumours or multiple tumours in one kidney are common. Angiomyolipomas begin in childhood in many individuals with TSC, but they usually grow very slowly and may not be problematic until young adulthood. Individuals with TSC should have their kidneys imaged at the time of diagnosis and then regularly throughout their lives.

TSC renal cysts are commonly multiple and bilateral. They are the second most frequently occurring kidney manifestation of TSC. Single or multiple renal cysts occur less often in individuals with TSC than do angiomyolipomas, but they may appear earlier. Some cysts may collapse and disappear.

TSC renal cysts are commonly multiple and bilateral. They are the second most frequently occurring kidney manifestation of TSC. Single or multiple renal cysts occur less often in individuals with TSC than do angiomyolipomas, but they may appear earlier. Some cysts may collapse and disappear.

One important research finding was the discovery of the TSC2 gene in close proximity to the gene for polycystic kidney disease (PKD1) on chromosome 16. A small group of individuals with TS have a large segment of chromosome 16 deleted which means that both the TSC2 and PKD1 genes are also removed. These individuals most often will have polycystic kidneys from birth and will require close monitoring and treatment throughout the childhood years.

Heart Involvement

Cardiac rhabdomyomas, are the most common primary cardiac tumour of tuberous sclerosis complex (TSC) in infancy and childhood. The incidence of these tumours in TSC has been reported to vary from 47 to 67%. They are sometimes be seen on ultrasound during pregnancy.

In most cases, cardiac tumours are their largest at birth and may shrink or disappear as the individual grows older. A second peak in the incidence of these tumours may occur during puberty. Electrocardiograms (ECGs) are used to detect abnormal heart rhythms or arrhythmias. Most rhabdomyomas of the heart are asymptomatic, but they should be treated by an experienced cardiologist if an arrhythmia or other cardiac problem is present.


Cardiac evaluation and screening is recommended for all patients with TSC.  Foetal echocardiography should be considered when rhabdomyomas are identified by prenatal ultrasound to detect individuals at high risk for heart failure after delivery. A baseline echocardiogram to image the heart and vascular structures is suggested for all patients, especially those younger than 3 years of age.

Arrhythmias may occur in patients with cardiac rhabdomyomas.  A baseline electrocardiogram (EKG) is recommended for all patients, and 24-hour ambulatory monitoring may also be done to further diagnose any rhythm disturbances and aid in their follow-up during the course of treatment.

Some rhabdomyomas result in clinical problems, monitoring by echocardiography every 1-3 years is recommended until regression of the tumours occurs.  More frequent or advanced diagnostic assessment may be required for symptomatic patients. Patients who have significant arrhythmias may require treatment with medication or a special cardiac catheterisation procedure.

Teeth Involvement

People with TSC may have dental pits and an overgrowth of the gums (fibromas) meaning teeth and gum tissue are slightly different and will require a little more care to keep them healthy. The tooth enamel may have random surface pits which may cause decay to occur more easily. A dentist can repair enamel pits.

Regular dental cleanings and x-ray check-ups to catch decay early, usually on a 6-month interval, are important. Your dentist may recommend recalls more frequent than 6 months based on you/your child’s risk for cavities. Children’s dentists (pediatric dentists) are trained in providing care to children and adults who may need sedation or extra behavioural care. Hospital dentistry is also an option if a patient cannot tolerate the regular office setting. 

Eye Involvement

There are three types of hamartomas (tumours) observed on the retina in TSC:

 1) smooth-surfaced hamartoma;

2) modular or “mulberry” hamartoma; and

3) transitional or mixed hamartoma that shows characteristics of both 1) and 2).

The frequency of retinal hamartomas in individuals with TSC has varied in reports from almost negligible to 87 percent of individuals, a difference probably reflecting the technique used and the expertise of the examiner. Although less common than the retinal hamartoma, a defect in the pigment of the iris has also been observed in some individuals with TSC. In addition, white depigmented patches, reminiscent of the hypopigmented macules on the skin, have also been observed on the retina of some individuals with TSC.

Retinal lesions may be difficult to identify without pupillary dilation and indirect ophthalmoscopy, particularly difficult to examine in uncooperative children. Most retinal hamartomas remain dormant, although occasionally individuals with TSC have visual impairment resulting from a large hamartoma in the macular region. Instances of visual loss following retinal detachment, vitreous haemorrhage, or hamartoma enlargement are rare.

The retinal hamartomas are benign and usually do not change over time. For the most part, treatment of the retinal lesions and repeated ophthalmologic examinations are unnecessary. Normal eye care should be maintained.


Cysts and tumours similar to those observed in the kidney sometimes appear in the liver, lung, pancreas, and ovaries. Biopsy of a suspicious lesion is recommended only when the lesion is unusually large, growing, causing symptoms, or exhibiting other suspicious characteristics. If they are symptomatic, they should be treated by the appropriate specialist and be removed if medically necessary.

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