Spastic paraplegia type 8 is part of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the lower limbs (paraplegia). Hereditary spastic paraplegias are divided into two types: pure and complex. The pure types involve only the nerves and muscles controlling the lower limbs and bladder, whereas the complex types also have significant involvement of the nervous system in other parts of the body. Spastic paraplegia type 8 is a pure hereditary spastic paraplegia.

Like all hereditary spastic paraplegias, spastic paraplegia type 8 involves spasticity of the leg muscles and muscle weakness. People with this condition can also experience exaggerated reflexes (hyperreflexia), a decreased ability to feel vibrations, muscle wasting (amyotrophy), and reduced bladder control. The signs and symptoms of spastic paraplegia type 8 usually appear in early to mid-adulthood. As the muscle weakness and spasticity get worse, some people may need the aid of a cane, walker, or wheelchair.

Mutations in the WASHC5 gene cause spastic paraplegia type 8. The WASHC5 gene provides instructions for making a protein called strumpellin. Strumpellin is active (expressed) throughout the body, although its exact function is unknown. The protein's structure suggests that strumpellin may interact with the structural framework inside cells (the cytoskeleton) and may attach (bind) to other proteins.

WASHC5 gene mutations are thought to change the structure of the strumpellin protein. It is unknown how the altered strumpellin protein causes the signs and symptoms of spastic paraplegia type 8.

Normal Function

The WASHC5 gene provides instructions for making a protein called strumpellin. Strumpellin is active (expressed) throughout the body, although its exact function is unknown. The protein's structure suggests that stumpellin may interact with the structural framework inside cells (the cytoskeleton) and may attach (bind) to other proteins.

Health Conditions Related to Genetic Changes

Spastic paraplegia type 8

At least three mutations in the WASHC5 gene have been found to cause spastic paraplegia type 8. These mutations change single building blocks (amino acids) in the strumpellin protein. One mutation that has been seen in multiple families replaces the amino acid valine with the amino acid phenylalanine at position 626 in strumpellin (written Val626Phe or V626F). WASHC5 gene mutations are thought to change the structure of the strumpellin protein. It is unknown how the altered strumpellin protein causes muscle weakness, muscle stiffness, and other features of spastic paraplegia type 8.

Cancers

Research has shown that the WASHC5 gene is abnormally active (overexpressed) in certain types of prostate cancer. Scientists do not know what causes this abnormal expression and have not determined whether the WASHC5 gene plays a role in the development of prostate cancer.

Other Names for This Gene

• KIAA0196
• MGC111053
• SPG8
• STRUM_HUMAN
• strumpellin

Genomic Location

Spastic paraplegia type 8 is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

In most cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

The prevalence of all hereditary spastic paraplegias combined is estimated to be 1 to 18 in 100,000 people worldwide. Spastic paraplegia type 8 likely accounts for only a small percentage of all spastic paraplegia cases.