Spastic paraplegia 4 (SPG4) is the most common type of hereditary spastic paraplegia (HSP) inherited in an autosomal dominant manner. Disease onset ranges from infancy to older adulthood. SPG4 is characterized by slowly progressive muscle weakness and spasticity (stiff or rigid muscles) in the lower half of the body. In rare cases, individuals may have a more complex form with seizures, ataxia, and dementia. SPG4 is caused by mutations in the SPAST gene. Severity of symptoms usually worsens over time, however some individuals remain mildly affected throughout their lives. Medications, such as antispastic drugs and physical therapy may aid in stretching spastic muscles and preventing contractures (fixed tightening of muscles).

In some cases, an affected person inherits the mutated gene from an affected parent. In other cases, the mutation occurs for the first time in a person with no family history of the condition. This is called a de novo mutation.

When a person with a mutation that causes an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit that mutation.

• Decreased ability to sense vibrations in the ankles
• Exaggerated reflexes (hyperreflexia)
• Ankle spasms
• High arches in the feet (pes cavus)
• Reduced bladder control
• Ataxia (lack of muscle control)
• Seizures

Some individuals may also experience a mild decline in cognitive function. This decline does not typically affect daily functioning.

The severity of symptoms in SPG4 generally worsen over time; however, some individuals may have mild symptoms throughout their lives. Approximately 17% of individuals eventually use a wheelchair, while approximately 20% use assistance (such as a walker) to walk.