Neurocutaneous syndromes

Neurocutaneous syndromes represent an heterogeneous group of genetic disorders characterized by simultaneous involvement of the central nervous system and the skin. Among the most relevant in the pediatric population are Neurofibromatosis type 1 (NF1), Tuberous Sclerosis Complex (TSC), Sturge-Weber Syndrome (SWS), and Incontinentia Pigmenti (IP). NF1, associated with pathogenic variants in NF1 gene, is characterized by café-au-lait macules, neurofibromas, and an increased risk of optic pathway glioma. TSC, resulting from mutations in TSC1 or TSC2 genes, presents with various types of skin lesions such as hypomelanotic macules and facial angiofibromas, along with cerebral, renal, ophthalmologic, and cardiac involvement, in addition to epilepsy and neurodevelopmental disorders. SWS is caused by somatic mutations in GNAQ gene and manifests with the characteristic port-wine stain, leptomeningeal angiomatosis, and glaucoma. IP, an X-linked condition caused by mutations in IKBKG, predominantly affects females and presents with stage-specific cutaneous lesions as well as potential neurological and ocular involvement. Early clinical recognition, often initiated through dermatological findings by the pediatrician, is crucial for timely diagnosis and intervention. Targeted therapies, such as mTOR or MEK inhibitors, are available for selected cases.