Hereditary Spastic Paraplegia (HSP)

Hereditary spastic paraplegia (HSP) refers to a group of inherited spinal cord disorders that are characterized by progressive weakness and spasticity (stiffness) of the legs. Gait difficulties are a typical early sign of the disease. These symptoms slowly progress and may eventually require assistance of a cane, walker, or wheelchair. Many people with HSP also have balance disturbance, or bladder and bowel problems. More complicated forms may be accompanied by additional symptoms including optic nerve atrophy, ataxia (lack of muscle coordination), epilepsy, cognitive impairment, peripheral neuropathy, and deafness. The diagnosis of HSP is primarily made by neurological examination and testing to rule out other disorders. HSP is caused by degeneration of the nerve pathways that carry signals from the brain down the spinal cord. The longest of these nerves are affected more severely, thus the pronounced stiffness in the legs compared to the arms.

Investigators at the Hussman Institute for Human Genomics (HIHG) have made significant contributions to the identification of gene that causes HSP. Dr. Pericak-Vance was involved in several studies that described new chromosomal locations for HSP and the discovery of the KIF5A gene. More recently, Dr. Zuchner discovered the REEP1 gene that is now established as the third most common HSP gene.

Current studies, led by Dr. Zuchner, focus on cell culture models for HSP to increase our understanding of the pathological processes that lead to this disease. We also actively enroll HSP patients and their families to identify the remaining genes, which account for ~40% of the disease. This research is supported by grants from the National Institute of Neurological Disorders and Stroke (NINDS) and the Hereditary Spastic Paraplegia Foundation.