Leukoencephalopathy with Vanishing White Matter (VWM) is an inherited disorder that affects the function of the brain and spinal cord. It is caused by chronic and progressive vanishing of the white matter, which consists of nerve fibers protected by surrounding fatty substance known as myelin. Most children affected with VWM appear normal at birth and may have slightly delayed development of motor skills such as crawling or walking. Major onset of symptoms begins in early childhood with progressive muscle stiffness and lack of voluntary muscle control, leading to difficulties walking and swallowing. Seizures, vision impairment and some intellectual impairment may also occur. Life expectancy ranges from one to five years after onset of symptoms to many years after onset. Progression of VWM in individuals is especially sensitive to stresses such as infection, mild head trauma or other injury, or even extreme fright. Specific changes in the brain as seen using magnetic resonance imaging (MRI) are characteristic of VWM, and may be visible before the onset of symptoms. More severe forms of VWM are less commonly seen, with symptoms appearing before birth or within the first year of life. Deterioration of the nervous system is rapid and death typically occurs within a few months of life to age two years. Mild forms also exist, with symptoms not appearing until adolescence or adulthood. In these cases, behavioral or psychiatric problems appear before neurologic symptoms appear. Affected females of all types may have underdeveloped ovaries that ultimately lead to ovarian failure if they survive into adolescence or adulthood. There is no cure for VWM; however medical surveillance and care may help to improve some symptoms and overall condition of life. VWM is caused by pathogenic variants in one of five genes, EIF2B1, EIF2B2, EIF2B3, EIF2B4, or EIF2B5, among which the pathogenic variants in EIF2B5 are most common.