Tuberous Sclerosis - Causes, Symptoms and Treatment Explained

Understanding Tuberous Sclerosis: Symptoms, Causes and Treatment

Your six-month-old daughter has been having seizures. The paediatrician noticed unusual light patches on her skin during examination. An MRI revealed small growths in her brain.

Tuberous sclerosis is a rare genetic disorder affecting thousands of families worldwide. Understanding it helps you navigate treatment decisions and provide the best care.

What is tuberous sclerosis?

Tuberous sclerosis is a rare genetic disorder causing non-cancerous tumour growths (hamartomas) in multiple organs, particularly the brain, kidneys, heart, lungs, and skin.

Tuberous sclerosis meaning comes from the characteristic brain lesions appearing as hard, tuber-like nodules (tubercles) with hardened tissue (sclerosis). These growths aren't cancer, though they can cause serious complications depending on size and location.

Tuberous sclerosis complex *(TSC) explained

The word "complex" reflects how this disorder affects multiple body systems simultaneously.

Medical professionals prefer this comprehensive term, and tuberous sclerosis syndrome is an older alternative.

Who can be affected by tuberous sclerosis?

Tuberous sclerosis age of onset

Tuberous sclerosis age of diagnosis varies widely.

• •Infants
  Cardiac tumours may be detected during prenatal ultrasound or shortly after birth. Infantile spasms often appear in the first year.
• •Children
  Seizures frequently emerge between the ages of 1-3. Developmental delays and autism spectrum features may become apparent during toddler years.
• •Adolescents
  Facial skin changes become more noticeable during teenage years.
• •Early signs
  Light-colored skin patches present at birth, seizures in infancy, or developmental delays prompt initial evaluation.

Tuberous sclerosis in adults

In adults, the disorder presents unique challenges. Many receive a diagnosis only after decades of unexplained symptoms.

• •Late diagnosis
  Adults may finally get answers after years of seizures, skin changes, or kidney problems attributed to other causes.
• •Adult-onset complications
  Kidney angiomyolipomas may grow larger and bleed. Lung involvement (LAM) primarily affects women.

Tuberous sclerosis causes

Genetic causes

Tuberous sclerosis causes involve specific genetic mutations that can be inherited or occur spontaneously.

• •Mutations in TSC1/TSC2 genes:
  Approximately two-thirds of cases result from new mutations, where neither parent carries the gene change. The remaining third inherit the mutation from an affected parent.
• •Inherited cases:
  When one parent has the condition, each child has a 50% chance of inheriting it. However, siblings with the same mutation may have vastly different symptom severity.

Tuberous sclerosis symptoms

Tuberous sclerosis symptoms vary enormously depending on which organs develop growths.

Brain and neurological symptoms

• •Seizures:
  Tuberous sclerosis seizures affect 80-90% of individuals. Types range from infantile spasms to focal seizures.
• •Developmental delays:
  Intellectual disability occurs in about 50% of cases.
• •Autism spectrum features:
  Behavioural and social challenges affect many children.

Brain and neurological symptoms

• •Seizures
  Tuberous sclerosis seizures affect 80-90% of individuals. Types range from infantile spasms to focal seizures.
• •Developmental delays
  Intellectual disability occurs in about 50% of cases.
• •Autism spectrum features
  Behavioural and social challenges affect many children.

Skin and external features

Tuberous sclerosis features on skin help with diagnosis:

• •Facial angiofibromas
  Small red bumps on cheeks and nose.
• •Hypopigmented patches
  Light-colored "ash leaf" spots, often present from birth.
• •Shagreen patches
  Raised, thickened skin areas on lower back.

Organ-related symptoms

• •Kidneys
  Renal cell carcinoma rarely develops, but angiomyolipomas (benign tumours) are common.
• •Lungs
  LAM causes progressive breathing difficulties, primarily in women.
• •Heart
  Cardiac rhabdomyomas often present in infants but typically shrink with age.
• •Vision
  Retinal hamartomas may affect vision if located critically.

Tuberous sclerosis associated tumours

The associated tumours are typically benign but can cause problems due to size or location.

• •Brain
  Subependymal nodules line the brain ventricles. Rarely, these develop into subependymal giant cell astrocytoma (SEGA), which can block fluid flow.
• •Kidneys
  Angiomyolipomas contain blood vessels, smooth muscle, and fat. Multiple growths are common.
• •Heart
  Rhabdomyomas may cause arrhythmias in newborns but usually regress.
• •Lungs
  LAM cysts develop exclusively in women, causing progressive lung damage.

How is tuberous sclerosis diagnosed?

Diagnosis becomes clear through specific diagnostic criteria and testing.

Tuberous sclerosis diagnostic criteria

Tuberous sclerosis diagnosis uses clinical criteria developed by international experts.

Tests used in tuberous sclerosis diagnosis

• •Genetic testing
  Identifies TSC1 or TSC2 mutations in 85% of cases.
• •MRI / CT scans
  Brain MRI reveals cortical tubers and nodules. Can cancer be detected in CT scan ? Yes, and CT/MRI also detect tuberous sclerosis brain lesions. Abdominal imaging evaluates kidney and liver involvement.
• •EEG
  Detects seizure activity and guides medication choices.
• •Ultrasound
  Cardiac ultrasound assesses heart tumours. Kidney ultrasound monitors angiomyolipoma growth.

Types and severity of tuberous sclerosis

Tuberous sclerosis types

The different types are classified by organ involvement:

• •Brain-predominant
  Primarily neurological symptoms
• •Kidney-predominant
  Multiple angiomyolipomas
• •Multi-system
  Three or more organ systems involved

TSC2 mutations generally cause more severe disease than TSC1.

Mild tuberous sclerosis

It is the cases with minimal symptoms, perhaps only skin changes or small kidney growths.

Even mild cases require ongoing surveillance, as complications can develop later. Annual kidney imaging and periodic brain MRI help detect emerging issues early.

Tuberous sclerosis treatment options

The treatment focuses on symptom management since no cure exists.

Medical treatment

• •Anti-seizure medications
  First-line treatment for epilepsy. Options include vigabatrin (for infantile spasms), levetiracetam, and lamotrigine.
• •mTOR inhibitors
  Everolimus and sirolimus reduce the growth of SEGAs, kidney angiomyolipomas, and facial angiofibromas.

Surgical treatments

• •Tumour removal
  Large kidney angiomyolipomas may require embolisation or surgical removal.
• •Epilepsy surgery
  For drug-resistant seizures, removing the brain region causing seizures may provide relief. Oncology doctors rarely manage this condition, but neurosurgeons provide specialised care.

Tuberous sclerosis complications

Here are some of the complications that vary by affected organs:

• •Uncontrolled seizures
  affect quality of life
• •Kidney failure
  from multiple angiomyolipomas
• •SEGA
  causing hydrocephalus
• •LAM
  leading to respiratory failure
• •Behavioural challenges
  requiring intensive support

Conclusion

This rare genetic disorder causes benign tumour growth due to TSC1 or TSC2 gene mutations, affecting 1 in 6,000 births.

Consult specialised medical teams for comprehensive evaluation.