Snapshot A 1-year-old boy presents to the pediatric emergency department with abnormal shaking. The parents decribe these shaking episodes as sudden and brief symmetric contractions of his upper and lower extremities. The infant sustains the contraction for a few seconds and subsequently relaxes. On physical examination he continues to have these spells and is treated with midazolam. Laboratory testing is unremarkable. After these episodes subside, he undergoes an EEG, which demonstrates hypsarrhythmia. An MRI brain with and without gadolinium testing demonstrates cortical dysplasia. Genetic testing is remarkable for a TSC1 mutation. Introduction Definition neurocutaneous autosomal dominant disease that can affect any organ Epidemiology Incidence neurologic disease is the most common cause of death renal disease is the second most common cause of death Etiology TSC1 mutation encodes hamartin on chromosome 9 TSC2 mutation encodes tuberin on chromosome 16 Pathogenesis normally, hamartin and tuberin form a complex that down regulates mTOR signaling when these proteins are disrupted, it leads to unregulated cell growth and proliferation, ultimately resulting in the formation of hamartomas in various locations Presentation Symptoms/physical exam central nervous system seizures secondary to cortical dysplasia (tubers) subependymal nodules subependymal giant cell astrocytomas can present as infantile spasms in infants and have hypsarrhythmias on EEG intellectual disability cardiac arrhythmias secondary to cardiac rhabdomyomas (common in infants) mitral regurgitation renal renal failure secondary to progressive enlargment of angiomyolipomas dermatologic facial angiofibromas hypomelanotic macules (Ash leaf spots) ungual fibromas shagreen patches Imaging MRI brain with and without gadolinium findings cortical tubers lesions in the ependymal lining of the third and fourth ventricles MRI of the abdomen findings may demonstrate renal angiomyolipomas Studies Genetic testing confirms the diagnosis Differential Other causes of seizures differentiating factors can be secondary to hypoglycemia hyper- or hyponatremia brain malignancy other seizure disorders (e.g., juvenile myoclonus) Treatment Medical corticotropin indication the treatment of choice of infantile spasms note that vigabatrin can be used as an alternative medication adrenocorticotropic hormone (ACTH) Complications Seizures Obstructive hydrocephalus End stage renal disease