Makindo Medical Notes

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 tumors 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 tumors 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 tumors of the heart), particularly in infancy.
  • Brain tumors, 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 tumors, 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 tumor surveillance, many patients can achieve a near-normal lifespan. The severity of neurological symptoms and tumor 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

• Tuberous Sclerosis - NCBI Bookshelf
• Tuberous Sclerosis Alliance