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Neurocutaneous disorders are diverse disorders that affect both the skin and nervous system (Table 10–1). Many either include or increase the risk of tumors as well. A careful history of neurologic symptoms with a thorough skin exam can often point to the diagnosis before genetic testing is obtained. Genetic testing can confirm the diagnosis when uncertain, assist in identifying additional familial cases not previously suspected, and facilitate family counseling and planning. The disorders in this group often result from mutations in 2 common pathways: mammalian target of rapamycin (mTOR, tuberous sclerosis) and Ras-mitogen–activated protein kinase (Ras-MAPK, neurofibromatosis type 1). Although there are several disorders in this category, focusing on a few of these disorders will allow the general pediatrician and pediatric neurologist to start treatment and screening early. Specifically, recent advances in these disorders provide opportunities for targeted therapies in patients.

Table 10–1.Neurocutaneous syndromes and common features.


Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder caused by mutations in the NF1 gene. It is the most common neurocutaneous syndrome with an incidence of 1 in approximately 3000. Mutations in the NF1 gene lead to decreased neurofibromin function, a GTPase that inhibits Ras. Loss of neurofibromin function leads to overactivation of the Ras-MAPK pathway and, ultimately, cell overgrowth.

Clinical Findings

Typical findings in NF1 include café-au-lait macules, axillary or inguinal freckling, Lisch nodules, neurofibromas, and optic gliomas. The most readily noticeable skin feature is café-au-lait macules, of which greater than 6 café-au-lait macules will be present. Children with fewer café-au-lait spots should be followed for growth and number of spots, which can increase over time in NF1. Axillary freckling or cutaneous fibromas in the presence of the café-au-lait spots confirms the diagnosis. However, other rare findings, including vascular lesions or bone lesions (eg, sphenoid dysplasia or tibial bowing/pseudoarthroses), can also be used to diagnose NF1 clinically. In the nervous system, neurofibromas are the hallmark feature. They are benign nerve sheath tumors on peripheral nerves. About one-third of patients can have plexiform neurofibromas, which arrive from nerve fascicules and plexuses. Plexiform neurofibromas may cause significant pain, lead to disfigurement, compromise of the surrounding tissue, and have malignant ...

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