Hereditary spastic paraplegia (SPG) is a group of neurodegenerative disorders characterized by progressive spasticity and weakness of the lower limbs, resulting from “dying back” axonopathy of the corticospinal tract. Pure and complicated forms are known, and loci with autosomal dominant, recessive, and X-linked patterns of inheritance were identified.
SPG7 is characterized by insidiously progressive bilateral lower limb weakness and spasticity (Tables 82.1 and 82.2). Most affected individuals have proximal or generalized weakness in the legs and impaired vibration sense. Onset is mostly in adulthood (ranging from 11 to 72 years). Clinical features of the disease include lower limb spasticity and weakness, spastic ataxic gait, hyperreflexia, extensor plantar responses, pyramidal signs, decreased vibratory sense in the lower limbs, degeneration of the lateral corticospinal tracts, cerebral white matter lesions, dysarthria, cognitive and memory deficits, cortical atrophy, and cerebellar atrophy. Additional features such as sphincter disturbances, dysphagia, pale optic disks, retinitis pigmentosa, nystagmus, strabismus, decreased hearing, scoliosis, and pes cavus may be observed. The disease is caused by mutations in the PGN gene, encoding paraplegin protein. The protein is located within the inner membrane of mitochondria and forms a complex called the m-AAA protease, which is responsible for assembling ribosomes and removing nonfunctional proteins in the mitochondria. Nonfunctional m-AAA proteases cause a buildup of unusable proteins in nerve cells, resulting in swelling of the cell, and reduced cell signaling and movement. Since the first molecular characterization, a number of patients have been clinically and genetically defined.
- Spastic paraparesis