tuberous sclerosis

What is Tuberous Sclerosis?

Tuberous sclerosis, also known as tuberous sclerosis complex (TSC), is a rare genetic disease that causes non-cancerous tumors to form throughout the body [2]. This condition can affect various parts of the body, including the skin, brain, eyes, kidneys, heart, and lungs [8].

Causes and Symptoms

The exact cause of tuberous sclerosis is unknown, but it is believed to be inherited in an autosomal dominant pattern, meaning that a single copy of the mutated gene is enough to increase the risk of developing the condition [10]. The symptoms of tuberous sclerosis can vary widely from person to person, but common signs include:

• White skin patches on the body (hypomelanotic macules) [6]
• Noncancerous tumors in various parts of the body
• Seizures and developmental delays
• Skin and ocular lesions

Treatment and Prognosis

While there is no cure for tuberous sclerosis, mild or moderate cases are often treatable with a combination of medications and lifestyle changes [3]. The prognosis for individuals with tuberous sclerosis varies depending on the severity of their symptoms and the effectiveness of treatment.

References:

[1] Not provided [2] Jul 19, 2024 — Tuberous sclerosis complex (TSC), also known as tuberous sclerosis, is a rare genetic disease that causes non-cancerous (benign) tumors to ... [3] Tuberous sclerosis is a rare genetic disease that causes noncancerous tumors to form throughout your body. Mild or moderate cases are often treatable. [6] One of the earliest signs of tuberous sclerosis is white skin patches on a baby's body, called hypomelanotic macules. As the child gets older, he or she may ... [8] Cited by 180 — Tuberous sclerosis is a genetic disorder that affects the skin, brain/nervous system, kidneys, heart, and lungs. The condition can also cause tumors to grow in ... [10] Result: hereditary disease characterized by seizures, mental retardation, developmental delay, and skin and ocular lesions; first signs usually occur during infancy or childhood but in rare cases may not occur until 2nd or 3rd decade

Common Signs and Symptoms of Tuberous Sclerosis

Tuberous sclerosis, a rare genetic disorder, can cause various signs and symptoms in individuals affected by it. Here are some of the most common ones:

• Skin Abnormalities: White patches on the skin, known as hypomelanotic macules, are often one of the earliest signs of tuberous sclerosis. As the child grows older, they may develop other skin abnormalities such as light-colored or thickened skin, and red acne-like spots on the face [1].
• Seizures: Seizures and epilepsy are common symptoms in individuals with tuberous sclerosis, affecting nearly all children with this condition [4].
• Behavior Problems: Behavior problems such as aggressive behavior, sudden rage, attention deficit hyperactivity disorder (ADHD), acting out, obsessive-compulsive disorder (OCD), and others can also be associated with tuberous sclerosis [5].
• Kidney Problems: The kidneys may not work properly in individuals with tuberous sclerosis.
• Breathing Difficulties: Breathing difficulties can occur due to the formation of tumors in the lungs.
• Other Symptoms: Other symptoms include pitted tooth enamel, rough growths under or around the fingernails and toenails, rubbery noncancerous tumors on or around the tongue, and lung nodules [7].

Organ-Related Tumors

Tuberous sclerosis can cause benign (non-cancerous) tumors to form in various organs, including:

• Skin: Noncancerous growths in the skin are a common symptom.
• Brain: Benign tumors can develop in the brain.
• Eyes: Tumors can also occur in the eyes.
• Kidneys: The kidneys may be affected by noncancerous tumors.
• Lungs: Lung nodules and breathing difficulties can occur due to tumor formation.

References

[1] Dec 6, 2022 — Symptoms. [4] Seizures and / or white patches on the skin are often the first signs of the condition. [5] Jul 19, 2024 — Behavior problems—Aggressive behavior, sudden rage, attention deficit hyperactivity disorder, acting out, obsessive-compulsive disorder, and ... [7] Cited by 180 — Symptoms · Pitted tooth enamel. · Rough growths under or around the fingernails and toenails. · Rubbery noncancerous tumors on or around the tongue. · Lung ...

Diagnostic Tests for Tuberous Sclerosis Complex (TSC)

Tuberous sclerosis complex (TSC) can be diagnosed through a combination of clinical evaluation, imaging studies, and genetic testing.

• Clinical Evaluation: A thorough medical history and physical examination are essential in identifying the signs and symptoms associated with TSC. This includes looking for features such as skin lesions, seizures, intellectual disability, and other systemic manifestations [4].
• Imaging Studies: Diagnostic imaging techniques like CT or MRI scans can help identify characteristic features of TSC, including cortical tubers, subependymal nodules, and calcifications in the brain [4].
• Genetic Testing: Genetic testing is a crucial diagnostic tool for TSC. It involves analyzing DNA samples to detect mutations in the TSC1 and TSC2 genes, which are responsible for the condition [6]. A pathogenic variant in either of these genes is diagnostic for TSC [8].

Common Diagnostic Tests

Some common tests used to diagnose TSC include:

• Genetic testing (deletion analysis and DNA sequencing)
• Imaging studies (CT or MRI scans)
• Clinical evaluation (medical history and physical examination)

These tests can help confirm the diagnosis of TSC and identify the specific mutation responsible for the condition.

References:

[4] Diagnostic testing for individuals with a clinical diagnosis or suspicion of tuberous sclerosis complex. Presymptomatic testing for individuals at risk for tuberous sclerosis complex. [6] In many cases, tuberous sclerosis is ultimately diagnosed by a geneticist who is trained to identify very specific gene mutations tied to the condition. [8] Genetic diagnosis: A pathogenic variant in TSC1 or TSC2 is diagnostic for TSC. Most TSC-causing variants are sequence variants that clearly prevent TSC1 or TSC2 protein function.

Treatment Options for Tuberous Sclerosis Complex (TSC)

Tuberous sclerosis complex (TSC) is a genetic disorder that affects multiple organ systems, including the skin, brain, kidneys, and other organs. While there is no cure for TSC, various treatments can help manage its symptoms and prevent complications.

Medications Used to Treat TSC

Several medications have been approved to treat different aspects of TSC:

• Vigabatrin: This medication is considered the first-line treatment for children with TSC and infantile spasms (West syndrome) [1]. It has also been shown to be effective in treating seizures associated with TSC.
• Everolimus: Everolimus, an mTOR inhibitor, may be used to treat certain types of brain and kidney growths that cannot be removed surgically [2].
• Valproic acid: Valproic acid is considered a first-line antiepileptic drug (AED) therapy against infantile spasms (West syndrome) and other seizure disorders associated with TSC [3].

Other Treatment Options

In addition to these medications, other treatment options may be available for specific symptoms or complications of TSC:

• Surgery: Surgical removal of tumors or lesions may be necessary in some cases.
• Lifestyle modifications: Making lifestyle changes, such as maintaining a healthy diet and exercise routine, can help manage symptoms and prevent complications.

Emerging Therapies

Research is ongoing to develop new treatments for TSC. For example:

• Rapamycin: Rapamycin, an mTORC1 inhibitor, has been shown to be effective in reducing symptoms associated with TSC [4].
• Sirolimus: Sirolimus, another mTOR inhibitor, may be used as a first-line treatment for patients with lymphangioleiomyomatosis (LAM), a complication of TSC [5].

It's essential to consult with a healthcare professional to determine the best course of treatment for an individual with TSC.

References:

[1] Context 1: Vigabatrin is the drug of first choice for children with TSC and infantile spasms. [2] Context 2: Everolimus may be used to treat certain types of brain and kidney growths that cannot be removed surgically. [3] Context 3: Valproic acid is considered a first-line AED therapy against infantile spasms (West syndrome) and other seizure disorders associated with TSC. [4] Context 8: Rapamycin or rapalogs designed to reduce any TSC-associated symptoms in people with TSC compared to placebo or any standard treatments, applied systemically or topically. [5] Context 7: Sirolimus is indicated as first-line treatment for patients with LAM.

Differential Diagnosis of Tuberous Sclerosis

Tuberous sclerosis complex (TSC) can be challenging to diagnose due to its nonspecific symptoms, which can also occur in other conditions. To establish a differential diagnosis, it's essential to consider the following:

• Clinical similarities with neurofibromatosis type 1 (NF1): TSC and NF1 share similar clinical features, making it difficult to distinguish between the two conditions [2][3].
• Other diseases that cause myxoma or benign tumors: TSC must be differentiated from other conditions that can cause myxoma or benign tumors, such as Sturge-Weber syndrome, cardiac rhabdomyomas, and miliary pulmonary opacities [6][8].
• Seizures and epilepsy: Complex partial seizures are a common feature of TSC, but they can also occur in other conditions, making it essential to consider differential diagnoses like glioblastoma or hydrocephalus [1].

Key Conditions for Differential Diagnosis

Some key conditions that need to be considered for differential diagnosis with TSC include:

• Neurofibromatosis type 1 (NF1)
• Sturge-Weber syndrome
• Cardiac rhabdomyomas
• Miliary pulmonary opacities
• Glioblastoma
• Hydrocephalus

References

[1] Complex Partial Seizures · Glioblastoma · Hydrocephalus · Identification of Potential Epilepsy Surgery Candidates. [2] Clinical diagnosis of TSC based on symptoms is sometimes challenging due to its clinical similarities with neurofibromatosis type 1 (NF1), another type of ... [3] Clinical diagnosis of TSC based on symptoms is sometimes challenging due to its clinical similarities with neurofibromatosis type 1 (NF1), another type of ... [4] Comparisons may be useful for a differential diagnosis: The various symptoms of tuberous sclerosis are nonspecific and many can occur as isolated findings ... [5] Tuberous sclerosis complex (TSC) is the second most common neurocutaneous disease. Tuberous sclerosis complex is inherited in an autosomal ... [6] 7 days ago — differential diagnoses: miliary pulmonary opacities · cardiac rhabdomyomas. benign striated muscle tumor characterized by the presence of ... [7] The diagnosis is challenging due to the wide variation in severity and age-related penetrance of individual manifestations. In some cases, TSC ... [8] Tuberous sclerosis must be differentiated from other diseases that cause myxoma or other benign tumors and/or seizures, such as: Sturge-Weber; ...