What is the differential diagnosis for a 10-year-old patient with seizures, café au lait spots, and a possible diagnosis of Tuberous Sclerosis Complex (TSC) versus another condition?

From the Guidelines

For a 10-year-old with seizures and café-au-lait spots, I strongly recommend a comprehensive workup to differentiate between neurofibromatosis type 1 (NF1) and tuberous sclerosis complex (TSC), with a priority on brain MRI to assess for cortical/subcortical tubers, subependymal nodules, and other neuronal migration defects, as suggested by the most recent guidelines 1. The evaluation should include a detailed skin examination, ophthalmologic evaluation, and genetic testing for NF1, TSC1, and TSC2 genes.

• Key features to look for in the skin examination include ash leaf spots, shagreen patches, and facial angiofibromas for TSC versus café-au-lait spots, axillary/inguinal freckling, and neurofibromas for NF1.
• Ophthalmologic evaluation should focus on detecting retinal hamartomas in TSC or Lisch nodules in NF1.
• Brain MRI is crucial for identifying tubers, subependymal nodules in TSC, and should be performed without contrast initially, reserving post-contrast imaging for characterization of lesions or high clinical concern for subependymal giant cell astrocytoma (SEGA) 1. Seizure management should proceed concurrently with first-line antiepileptic drugs.
• Additional evaluations should include renal ultrasound for angiomyolipomas in TSC, echocardiogram for cardiac rhabdomyomas in TSC, and developmental assessment. The distinction between NF1 and TSC is critical because TSC requires more extensive multisystem monitoring and may benefit from mTOR inhibitors like everolimus for specific manifestations, whereas NF1 management focuses on different complications 1.

From the Research

Seizure Workup in a 10-year-old with Café au Lait Spots

• A 10-year-old patient presenting with seizures and café au lait spots may require a comprehensive workup to determine the underlying cause of their symptoms 2, 3.
• Café au lait spots are a common feature of neurofibromatosis type 1 (NF1), but they can also be found in other conditions, such as Legius syndrome, and in healthy individuals 4, 5.
• The presence of six or more café au lait spots is a criterion for the diagnosis of NF1, but recent studies suggest that a significant percentage of individuals with multiple café au lait spots do not have NF1 3.

Differential Diagnosis

• The differential diagnosis for a 10-year-old patient with seizures and café au lait spots includes:
  • Neurofibromatosis type 1 (NF1)
  • Tuberous sclerosis complex (TSC)
  • Legius syndrome
  • Other genetic disorders
  • Benign conditions, such as familial café au lait spots 2, 6

Diagnostic Evaluation

• A comprehensive diagnostic evaluation should include:
  • Physical examination to look for other signs of NF1 or TSC, such as skin lesions, bone abnormalities, or eye abnormalities
  • Imaging studies, such as MRI or CT scans, to evaluate for any structural abnormalities in the brain
  • Electroencephalogram (EEG) to evaluate for any abnormal electrical activity in the brain
  • Genetic testing to evaluate for mutations in the NF1 or TSC1/2 genes 3, 5