Related Subjects:
|Brain tumour s
|Astrocytomas
|Brain Metastases
|Tuberous sclerosis
|Turcot's syndrome
|Lhermitte Duclos Disease
|Oligodendroglioma
|Acute Hydrocephalus
|Intracranial Hypertension
|Primary CNS Lymphoma (PCNSL)
Note: Café-au-lait spots are commonly associated with Neurofibromatosis but can also be present in patients with Tuberous Sclerosis.
About
- Tuberous Sclerosis: An autosomal dominant genetic disorder with a prevalence of approximately 1 in 10,000. It is characterized by benign tumours in multiple organ systems, including the skin, brain, kidneys, and heart.
Genetics
- TSC1 Gene: Located on chromosome 9, codes for the protein hamartin.
- TSC2 Gene: Located on chromosome 16, codes for the protein tuberin. Mutations in either gene lead to dysregulation of cell growth and development, resulting in hamartomas.
Clinical Features
- Renal Involvement:
- Angiomyolipomas - benign tumours composed of blood vessels, muscle, and fat.
- Increased risk of renal cell carcinoma.
- Skin Manifestations:
- Ash Leaf Spots: Hypopigmented macules best seen under ultraviolet (UV) light using a Wood's lamp.
- Shagreen Patch: Thickened, rough yellowish patches typically found on the lower back.
- Adenoma Sebaceum: Red or pink papules on the face, particularly around the nose and cheeks.
- Ungual Fibromas: Small, flesh-colored growths around the nails, especially the toenails.
- Neurological Manifestations:
- Seizures or epilepsy, which may be difficult to control.
- Cardiac rhabdomyomas (benign tumours of the heart), particularly in infancy.
- Brain tumours, such as subependymal giant cell astrocytomas (SEGAs), which may cause hydrocephalus if they obstruct CSF flow.
- Learning disabilities and intellectual impairment.
- Other Manifestations:
- Polycystic kidney disease, although rare without associated PKD1 gene mutation.
- Rarely causes pleural complications, such as milky pleural effusion or pneumothorax.
- Tumor Risks:
- Subependymal giant cell astrocytomas (SEGAs) - typically arise in childhood and may require surgical intervention if symptomatic.
- Rhabdomyomas - benign heart tumours, most common in infants with Tuberous Sclerosis.
Investigations
- Imaging: MRI or CT scan often shows calcified subependymal nodules along the lateral ventricles. These nodules may progress into SEGAs.
- Genetic Testing: Can confirm mutations in TSC1 or TSC2 for a definitive diagnosis, especially in cases with atypical presentation.
Prognosis
- Normal Lifespan: With regular monitoring and tumour surveillance, many patients can achieve a near-normal lifespan. The severity of neurological symptoms and tumour complications can affect quality of life.
Management
- Genetic Counseling: Essential for family planning and understanding the hereditary nature of Tuberous Sclerosis.
- Supportive Care: Multidisciplinary support for managing neurological, renal, and skin symptoms.
- Hydrocephalus Management: Ventriculoperitoneal (VP) shunt placement may be necessary if hydrocephalus develops from SEGAs or other obstructions.
- Anticonvulsants: Used to manage epilepsy. Seizure control can be challenging and may require multiple medications.
- mTOR Inhibitors: Medications such as everolimus may be prescribed to reduce the size of renal angiomyolipomas and SEGAs by targeting the mTOR pathway affected by TSC1 and TSC2 mutations.
- Regular Screening: Ongoing screening for renal, neurological, and cardiac complications is essential for early detection and intervention.
References