Tuberous sclerosis

Synonyms

8

Overview

Tuberous sclerosis complex is a genetic disorder characterized by the growth of numerous noncancerous (benign) tumors in many parts of the body. These tumors can occur in the skin, brain, kidneys, and other organs, in some cases leading to significant health problems. Tuberous sclerosis complex also causes developmental problems, and the signs and symptoms of the condition vary from person to person.

Virtually all affected people have skin abnormalities, including patches of unusually light-colored skin, areas of raised and thickened skin, and growths under the nails. Tumors on the face called facial angiofibromas are also common beginning in childhood.

Tuberous sclerosis complex often affects the brain, causing seizures, behavioral problems such as hyperactivity and aggression, and intellectual disability or learning problems. Some affected children have the characteristic features of autism, a developmental disorder that affects communication and social interaction. Benign brain tumors can also develop in people withtuberous sclerosis complex; these tumors can cause serious or life-threatening complications.

Kidney tumors are common in people with tuberous sclerosis complex; these growths can cause severe problems with kidney function and may be life-threatening in some cases. Additionally, tumors can develop in the heart, lungs, and the light-sensitive tissue at the back of the eye (theretina).

Symptoms

Tuberous sclerosis symptoms include noncancerous tumors or other lesions that grow in many parts of the body, but most commonly in the brain, kidneys, heart, lungs and skin. Symptoms can range from mild to severe.Tuberous sclerosis signs and symptoms vary, depending on where the tumors or other lesions develop:

  • Skin abnormalities. Some people with tuberous sclerosis have patches of light-colored skin, or they may develop small, harmless areas of thickened skin, or growths under or around the nails. Facial lesions that resemble acne also are common and can be treated.
  • Seizures. Lesions in the brain may be associated with seizures, which can be the first symptom of tuberous sclerosis. In small children, a common type of seizure called infantile spasm shows up as repetitive spasms of the head and legs.
  • Developmental delays. Tuberous sclerosis can be associated with intellectual disability, learning disabilities or developmental delays.
  • Behavior problems. Common behavior problems may include hyperactivity, raging outbursts, aggression, repetitive behaviors, or social and emotional withdrawal.
  • Communication and social interaction problems. Some children with tuberous sclerosis have trouble with communication and social interaction. And some children may have autism spectrum disorder.
  • Kidney problems. Most people with tuberous sclerosis develop lesions on their kidneys, and they may develop more lesions as they age, sometimes damaging kidney function.
  • Heart problems. These lesions, if present, are usually largest at birth and shrink as the child gets older.
  • Lung problems. Lesions that develop in the lungs (pulmonary leiomyomas) may cause coughing or shortness of breath, especially with physical activity or exercise.
  • Eye abnormalities. Lesions can appear as white patches on the light-sensitive tissue at the back of the eye (retina). These do not always interfere with vision.
  • Adenoma sebaceum
  • EEG abnormality
  • Neoplasm of the nervous system

Causes

Tuberous sclerosis is a genetic disease caused by mutations in the TSC1 or TSC2 gene. Normally, these genes are thought to prevent cells from growing too fast or in an uncontrolled manner. Mutations in either of these genes can cause cells to divide excessively, which leads to numerous lesions throughout the body.

Prevention

About one-third of people who have tuberous sclerosis inherit an altered TSC1 or TSC2 gene — the genes associated with tuberous sclerosis — from a parent who has the disease. About two-thirds of people who have tuberous sclerosis have a new mutation in either the TSC1 or TSC2 gene.

If you have tuberous sclerosis, you have up to a 50 percent chance of passing the condition to your biological children. Severity of the condition may vary. A parent who has tuberous sclerosis may have a child who has a milder or more severe form of the disorder., therefore genetic counselling is advised.

Diagnosis

There are no pathognomonic clinical signs for tuberous sclerosis. Many signs are present in individuals who are healthy (although rarely), or who have another disease. A combination of signs, classified as major or minor, is required in order to establish a clinical diagnosis.

In infants, the first clue is often the presence of seizures, delayed development or white patches on the skin. A full clinical diagnosis involves

  • Taking a personal and family history.
  • Examining the skin under a Wood's lamp (hypomelanotic macules), the fingers and toes (ungual fibroma), the face (angiofibromas) and the mouth (dental pits and gingival fibromas).
  • Cranial imaging with non enhanced CT or, preferably, MRI (cortical tubers and subependymal nodules).
  • Renal ultrasound (angiomyolipoma or cysts).
  • An echocardiogram in infants (rhabdomyoma).
  • Fundoscopy (retinal nodular hamartomas or achromic patch).

The various signs are then marked against the diagnostic criteria to produce a level of diagnostic certainty:

  • Definite – Either two major features or one major feature plus two minor features.
  • Probable – One major plus one minor feature.
  • Suspect – Either one major feature or two or more minor features.

Due to the wide variety of mutations leading to TSC, there are no simple genetic tests available to identify new cases. Nor are there any biochemical markers for the gene defects. However, once a person has been clinically diagnosed, the genetic mutation can usually be found. The search is time-consuming and has a 15% failure rate, which is thought to be due to somatic mosaicism. If successful, this information can be used to identify affected family members, including prenatal diagnosis. As of 2006, preimplantation diagnosis is not widely available.

Prognosis

The prognosis for individuals with TSC depends on the severity of symptoms

Depending on where the tumors or other lesions develop and their size, they can cause severe or life-threatening complications. Here are some examples of complications.

  • Lesions in the brain known as subependymal giant cell astrocytomas (SEGAs) can block the flow of cerebral spinal fluid within the brain. This blockage can cause the buildup of fluid in the cavities — ventricles — deep within the brain (hydrocephalus) with various signs and symptoms, including nausea, headaches and behavior changes.
  • Lesions in the heart, usually in infants, can block blood flow or cause problems with heart rhythm (dysrhythmia).
  • Lesions in the kidney can be large and cause potentially serious — even life-threatening — kidney problems. Lesions in the kidney can cause bleeding or lead to kidney failure. Rarely, kidney lesions can become cancerous.
  • Lesions in the lungs can lead to lung failure.
  • Lesions in the eye can interfere with vision if they block too much of the retina, though this is rare.

Detection of the disease should prompt one for genetic counselling. It is also important to know that even though the disease does not have a cure, symptoms can be treated symptomatically. Hence, awareness regarding different organ manifestations of tuberous sclerosis is important.

Treatment

There's no cure for tuberous sclerosis, but treatment can help manage specific signs and symptoms. For example:

  • Medication. Anti-epileptic drugs may be prescribed to control seizures, and other medications may help manage behavior problems. Everolimus (Afinitor, Zortress) may be used to treat certain types of brain growths and kidney tumors that can't be surgically removed in people with tuberous sclerosis. The topical ointment form of a drug called sirolimus may help treat acne-like skin lesions that can occur in tuberous sclerosis.
  • Educational therapy. Early intervention can help children make adaptations to developmental delays and meet their full potential in the classroom.
  • Occupational therapy. Through occupational therapy, a person who has tuberous sclerosis can improve his or her ability to handle daily tasks.
  • Psychological therapy. Talking with a mental health therapist may help you or your child accept and adjust to living with this disorder.
  • Surgery. If a lesion affects the ability of a specific organ — such as the kidney or heart — to function, the lesion may be surgically removed. Sometimes surgery helps control seizures caused by brain lesions that don't respond to medication. Surgical procedures such as dermabrasion or laser treatment may improve the appearance of skin lesions.

Tuberous sclerosis is a lifelong condition that requires careful monitoring and follow-up because many signs and symptoms may take years to develop. With appropriate care, however, many people who have tuberous sclerosis lead full, productive lives and enjoy a normal life expectancy.

Resources

http://www.tsalliance.org/