Spastic paraplegia type 2 belongs to a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by muscle stiffness (spasticity) and weakness that worsens over time and paralysis of the lower limbs (paraplegia). Hereditary spastic paraplegias are divided into two types: pure and complex. The pure (also called uncomplicated) types only involve the legs. The complex (also called complicated) types involve the lower limbs and can also affect the upper limbs to a lesser degree. The complex type can also affect the structure or function of the brain. It can also affect the network of nerves (the peripheral nervous system) that connects the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound.

Variants (also called mutations) in the PLP1 gene cause spastic paraplegia type 2. The PLP1 gene provides instructions for producing proteolipid protein 1 and a modified version (isoform) of that protein, called DM20.  Proteolipid protein 1 and DM20 are primarily located in the brain and spinal cord (the central nervous system) and are the main proteins found in myelin, the fatty covering that insulates nerve fibers.

There are more than 80 different types of hereditary spastic paraplegia, and the combined prevalence of all these types is estimated to be 1 to 18 in 100,000 people worldwide. Spastic paraplegia type 2 likely accounts for only a small percentage of all hereditary spastic paraplegia cases.

This condition is inherited in an X-linked pattern. A condition is considered X-linked if the altered gene that causes the disorder is located on the X chromosome, which is one of the two sex chromosomes in each cell. In males (who have only one X chromosome), a variant in the only copy of the gene in each cell is sufficient to cause the condition. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Published Date: September 04, 2025
Published By: National Institutes of Health