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. 

Spastic paraplegia type 2 can be classified as either pure or complex, depending on the signs and symptoms. The pure type of this condition is more common. The complex type of spastic paraplegia type 2 is sometimes called hypomyelination of early myelinating structures (HEMS).

People with the pure type of spastic paraplegia type 2 experience spasticity in the leg muscles. Over time, affected individuals may lose the ability to walk. Some affected individuals may also have poor bladder control. The signs and symptoms of spastic paraplegia type 2 usually appear between the ages of 1 and 5 years, but it can develop later in life. Individuals with spastic paraplegia type 2 typically have a normal lifespan.

In addition to leg spasticity and poor bladder control, people with HEMS can also experience problems with movement and balance (ataxia); involuntary movements of the eyes (nystagmus); and involuntary, rhythmic shaking (tremor). They may also have mild intellectual disabilities and degeneration (atrophy) of the optic nerves, which carry information from the eyes to the brain. The signs and symptoms of HEMS also typically appear between the ages of 1 and 5 years. Individuals with HEMS usually survive into mid to late adulthood.

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.

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.  

The variants in the PLP1 gene that cause spastic paraplegia type 2 cause cells to produce a smaller amount of functional proteolipid protein 1. These changes typically affect the production of proteolipid protein 1 but not DM20. As a result, the central nervous system is able to form some myelin, though it produces less myelin than normal (hypomyelination). People with HEMS typically have more severe hypomyelination than people with the pure type of spastic paraplegia type 2. If nerve fibers are not properly myelinated during development, the nervous system does not function as it should, resulting in the signs and symptoms of spastic paraplegia type 2.

Genetic Testing Information

• Genetic Testing Registry: Hereditary spastic paraplegia 2

Genetic and Rare Diseases Information Center

• Hereditary spastic paraplegia
• Spastic paraplegia type 2

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Catalog of Genes and Diseases from OMIM

• SPASTIC PARAPLEGIA 2, X-LINKED; SPG2

Scientific Articles on PubMed

• PubMed

• Boespflug-Tanguy O. Inborn errors of brain myelin formation. Handb Clin Neurol. 2013;113:1581-92. doi: 10.1016/B978-0-444-59565-2.00027-7. Citation on PubMed
• Cailloux F, Gauthier-Barichard F, Mimault C, Isabelle V, Courtois V, Giraud G, Dastugue B, Boespflug-Tanguy O. Genotype-phenotype correlation in inherited brain myelination defects due to proteolipid protein gene mutations. Clinical European Network on Brain Dysmyelinating Disease. Eur J Hum Genet. 2000 Nov;8(11):837-45. doi: 10.1038/sj.ejhg.5200537. Citation on PubMed
• Cao Y, Zheng H, Zhu Z, Yao L, Tian W, Cao L. Clinical and Genetic Spectrum in a Large Cohort of Hereditary Spastic Paraplegia. Mov Disord. 2024 Apr;39(4):651-662. doi: 10.1002/mds.29728. Epub 2024 Jan 31. Citation on PubMed
• Hedera P. Uncomplicated (Pure) Hereditary Spastic Paraplegia Overview. 2000 Aug 15 [updated 2025 Jun 5]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK1509/ Citation on PubMed
• Khalaf G, Mattern C, Begou M, Boespflug-Tanguy O, Massaad C, Massaad-Massade L. Mutation of Proteolipid Protein 1 Gene: From Severe Hypomyelinating Leukodystrophy to Inherited Spastic Paraplegia. Biomedicines. 2022 Jul 15;10(7):1709. doi: 10.3390/biomedicines10071709. Citation on PubMed
• Wolf NI, van Spaendonk RML, Hobson GM. PLP1-Related Disorders. 1999 Jun 15 [updated 2025 Jun 12]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK1182/ Citation on PubMed
• Yao L, Zhu Z, Zhang C, Tian W, Cao L. PLP1 gene mutations cause spastic paraplegia type 2 in three families. Ann Clin Transl Neurol. 2023 Mar;10(3):328-338. doi: 10.1002/acn3.51722. Epub 2023 Jan 9. Citation on PubMed