Inherited variations and de novo mutations cause phenotypes spanning from spastic paraplegia over neurodevelopmental delay and progressive neurological disease to a severe lethal leukodystrophy. Graded according to severity and age of onset, these classify into three phenotypic groups: (1) spastic paraplegia with onset at around 40, (2) neurological and developmental disorders noticed from early childhood on deteriorating with age, and (3) lethal hypomyelinating leukodystrophy. The first group so-far comprises only one family in which heterozygosity for a specific missense variant is associated with the disease. The second group is associated with de novo mutations at a number of amino acid positions, and the third group is caused by homozygosity for a missense variant. A common finding in the neurodevelopmental and lethal forms is hypomyelination of the brain as visualized using MRI.
HSPD1