Neurofibromatosis type 1: natural history and impact on quality of life

Neurofibromatosis Type 1 (NF1, von Recklinghausen’s disease) is among the more common autosomal dominant genetic disorders, with a worldwide incidence of approximately 1 in 3000 live births. NF1 can occur as either an inherited defect or as a spontaneous “de novo” mutation. NFI is caused by mutation of the neurofibromin gene that leads to a lack of neurofibromin in the cytoplasm of the cell. Neurofibromin, among other cytoplasmic roles, is a key regulator of certain cellular growth pathways. There is currently no cure for NF1. The disorder has an almost 100% penetrance, but is widely variable in its manifestation. NF1 is a progressive multisystem disorder, and the clinical manifestations tend to worsen with advancing age. NF1 typically manifests as multiple benign skin tumors (neurofibromas), café-au-lait spots, axillary freckles, optical nerve gliomas, iris hamartomas (Lisch nodules), learning disabilities, speech impairment, and orthopedic and cardiovascular problems. More severe manifestations can cause vision loss, headaches, seizures, chronic pain, and orthopedic problems limiting physical activity. Patients with NF1 are four times more likely to develop malignancies than the general population. Several studies have shown that NF1 impairs the patient’s quality of life through association with more severe complications, impacts on the patient’s appearance, and through learning disabilities and depression. In both mild and severe cases, there seemed to be an equal emotional impact on the patient. The psychosocial impact manifests in various ways, including loss of confidence and self-esteem. This can stem from insecurity due to an underlying learning disability or insecurity due to NF1-related cosmetic damage. The academic and emotional damage that follow the learning disability or the lack of confidence, if not treated with appropriate therapy, can go on to impact the patient’s relationships and career. The patient may suffer from social exclusion, financial hardship and inability to obtain health insurance. Patients may be unwilling to have children out of fear of passing on the mutation. This thesis seeks to present in detail the impacts on quality of life that neurofibromatosis causes, and discuss current management and treatment strategies that exist and what can be done further to improve these people’s lives. Early individualized treatment is necessary to achieve better outcomes. Support groups can help educate NF1 patients and their family members and may help alleviate stress. Widespread public education about the condition would help remove the public stigma of Nf1, and allow for patients to feel normal and valued in society. Early individualized treatment is necessary to achieve better outcomes