From the Guidelines
For a 10-year-old with seizures and café-au-lait spots, a comprehensive workup focusing on neurofibromatosis type 1 (NF1) is crucial, given the high prevalence of NF1 and its association with seizures and skin manifestations, as highlighted in the 2024 update on pediatric cancer surveillance recommendations 1. The evaluation should include:
- A detailed neurological examination to identify any focal neurological deficits
- A skin examination for additional cutaneous findings such as axillary freckling, Lisch nodules, or hypopigmented macules
- A family history assessment to identify any relatives with similar features or diagnosed with NF1
- Neuroimaging with MRI of the brain to identify potential structural abnormalities, tumors, or cortical dysplasias, as whole-body magnetic resonance imaging (WB-MRI) has proven its efficacy in detecting neurofibromas in NF1 patients 1
- An EEG to characterize the seizures and determine the best course of treatment
- Genetic testing for NF1 mutations, as it is an essential tool in confirming the diagnosis and guiding management
- Ophthalmologic evaluation to identify ocular manifestations of NF1, such as optic gliomas For seizure management, levetiracetam (starting at 10-20 mg/kg/day divided twice daily, maximum 60 mg/kg/day) or oxcarbazepine (8-10 mg/kg/day initially, titrated to 30-45 mg/kg/day divided twice daily) are reasonable first-line options while the diagnostic workup proceeds, considering the potential for seizures to be a manifestation of a broader syndrome requiring comprehensive care. Multidisciplinary care involving neurology, genetics, dermatology, and ophthalmology is essential for optimal management of NF1, as emphasized in the recent update on pediatric cancer surveillance recommendations 1.
From the Research
Seizure Workup in a 10-year-old with Café au Lait Spots
- A 10-year-old with café au lait spots presenting with seizures may require a comprehensive workup to rule out underlying conditions such as neurofibromatosis type 1 (NF1) or Legius syndrome 2, 3.
- Café au lait spots are a common feature of NF1, but they can also be present in other conditions, including Legius syndrome, and may not be pathognomonic for NF1 4.
- The presence of multiple café au lait spots may warrant investigation to identify an underlying disease, including NF1, neurofibromatosis type 2, McCune-Albright syndrome, and neurofibromatosis type 1-like syndrome 5.
- Seizure risk is known to be elevated in NF1, and recent studies suggest that seizure risk may also be increased in Legius syndrome, although the epilepsy prognosis appears to be generally good 3.
- A thorough diagnostic evaluation, including genetic testing, may be necessary to determine the underlying cause of the seizures and café au lait spots, and to guide management and follow-up 2, 6.
Differential Diagnosis
- Neurofibromatosis type 1 (NF1): characterized by multiple café au lait spots, freckling, and neurofibromas 2, 4.
- Legius syndrome: a rare genetic disorder caused by heterozygous SPRED1 pathogenic variants, which shares phenotypic features with NF1, including café au lait spots and axillary freckling 3.
- Familial café au lait spots: a variant of NF1, which may be allelic to NF1 and fully penetrant, but does not confer a risk of other NF1 symptoms 6.
- Neurofibromatosis type 6: a proposed diagnosis for multiple or familial café-au-lait spots without other stigmata of NF1 or evidence of other systemic disease 5.