In most instances, neurofibromatosis type 1 can be diagnosed clinically according to consensus criteria and genetic testing is only used in atypical presentations or for family planning decisions.Café au lait spots are one of the most characteristic features of neurofibromatosis type 1. They are hyperpigmented lesions of the skin that increase in number and size during the first years of life. They are present in almost all patients but do not have malignant potential. Freckling in the axillary and inguinal regions are another common presenting feature seen in as many as 90% of patients during childhood. Lisch nodules (benign hamartomas of the iris) are seen in almost all patients but they do not cause any visual or ocular impairment. Neurofibromas are benign nerve sheath tumors that occur in peripheral nerves. These typically develop during the teenage years. Neurofibromas do not become malignant but can cause cosmetic concerns as well as local pruritus. When present in the spine they can affect nerve roots and result in both motor and sensory defects. Surgery may be required in some cases. On the contrary, plexiform neurofibromas arise from multiple nerve fascicles and malignant transformation occurs in approximately 10% of cases. They may result in significant morbidity as they may cause organ compression, vascular occlusions, bone destruction, pain and cosmetic issues. Plexiform neurofibromas are seen in 30-50% of patients.Optic pathway gliomas are seen in 15-20% of patients with neurofibromatosis type 1. They most often arise during childhood.
This leads to impaired regulation of cellular proliferation, survival, homeostasis, migration and other critical functions. The most typically affected organs include the brain, skin, kidney, heart and lung. The incidence of TSC is approximately 1 in 6,000 live births. Similar to other neurocutaneous disorders there is variable penetrance and expressivity. TSC1 mutations tend to have a less severe phenotype and are more likely to be familial. A major development in the treatment of this condition occurred in 2010s when the FDA approved mTOR inhibitors for the treatment of several manifestations of TSC. Epilepsy is among the most common manifestations of TSC and it occurs 80-90% of patients. It usually presents during the first few years of life and is medically refractory in two-thirds of patients. Approximately, one-third of patients have infantile spasms. There are several types of brain lesions that can be found in TSC including subependymal nodules (SENs), cortical tubers and subependymal giant cell astrocytomas (SEGAs). SENs and cortical tubers occur in approximately 80% and 90% of patients, respectively. SEGAs occur in 10-15% of patients and are a major potential cause of morbidity and potentially mortality. They tend to present during the first 20 years of life. TSC-Associated Neuropsychiatric Disorder (TAND) refers to the behavioral, intellectual and psychiatric manifestations of TSC including autism spectrum disorder, attention deficit hyperactivity disorder, intellectual disability, depression and anxiety. Approximately 90% of patients will have at least 1 symptom of TAND.Lymphangioleiomyomatosis (LAM) occurs in the lung and may result in pneumothorax, cystic lung destruction and pleural effusions.