Spastic paraplegia type 15
Spastic paraplegia type 15 is a complex genetic disorder characterized by progressive muscle stiffness, paralysis of the lower limbs, and additional neurological and developmental features.
Overview
Spastic paraplegia type 15 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). It is classified as a complex hereditary spastic paraplegia because it involves all four limbs as well as additional features, including abnormalities of the brain. The condition also affects the peripheral nervous system, which connects the brain and spinal cord to muscles and sensory cells.
Symptoms
Symptoms usually become apparent in childhood or adolescence. Common features include:
- Weak muscle tone (hypotonia)
- Difficulty walking
- Intellectual disability
- Abnormal thinning of the tissue connecting the left and right halves of the brain
- Loss (atrophy) of nerve cells in the cerebral cortex and cerebellum
- Numbness, tingling, or pain in the arms and legs (sensory neuropathy)
- Impairment of the nerves that control movement (motor neuropathy)
- Exaggerated reflexes (hyperreflexia) of the lower limbs
- Muscle wasting (amyotrophy)
- Reduced bladder control
- Pigmentary maculopathy, an eye condition that impairs vision
Rarely, individuals may experience parkinsonism, which includes tremors, rigidity, and unusually slow movement (bradykinesia). As the condition progresses, many people experience a decline in intellectual ability and require walking aids or wheelchair assistance in adulthood.
Causes
Mutations in the ZFYVE26 gene cause spastic paraplegia type 15. This gene provides instructions for making a protein called spastizin, which is essential for autophagy—the process of recycling worn-out cell parts and unneeded proteins. Mutations often result in a shortened, non-functional protein, leading to the accumulation of unneeded materials within cells, which causes cell dysfunction and death.
Inheritance
This condition is inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell have mutations. Parents of an affected individual typically carry one copy of the mutated gene but do not show signs or symptoms of the condition.