Spastic Paraplegia Type 4 Overview
Learn About Spastic Paraplegia Type 4
Spastic paraplegia type 4 (also known as SPG4) is the most common of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) in the legs and difficulty walking. Hereditary spastic paraplegias are divided into two types: pure and complex. The pure types generally involve only spasticity of the lower limbs and walking difficulties. The complex types involve more widespread problems with the nervous system; the structure or functioning of the brain; and the nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound (the peripheral nervous system). In complex forms, there can also be features outside of the nervous system. Spastic paraplegia type 4 is usually a pure hereditary spastic paraplegia, although a few complex cases have been reported.
Mutations in the SPAST gene cause spastic paraplegia type 4. The SPAST gene provides instructions for producing a protein called spastin. Spastin is found throughout the body, particularly in certain nerve cells (neurons). The spastin protein plays a role in the function of microtubules, which are rigid, hollow fibers that make up the cell's structural framework (the cytoskeleton). Microtubules are also involved in transporting cell components and facilitating cell division. Spastin likely helps restrict microtubule length and disassemble microtubule structures when they are no longer needed. Mutations in spastin impair the microtubules' ability to transport cell compartments (organelles), especially in nerve cells; researchers believe this contributes to the major signs and symptoms of spastic paraplegia type 4.
The prevalence of spastic paraplegia type 4 is estimated to be 2 to 6 in 100,000 people worldwide.
This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
Marcondes Franca practices in Campinas, Brazil. Franca is rated as an Elite expert by MediFind in the treatment of Spastic Paraplegia Type 4. Their top areas of expertise are Spastic Paraplegia Type 4, Spinocerebellar Ataxia, Spinocerebellar Ataxia Type 3, and Spastic Paraplegia Type 7.
Iscia Cendes-Lopes practices in Campinas, Brazil. Cendes-Lopes is rated as an Elite expert by MediFind in the treatment of Spastic Paraplegia Type 4. Their top areas of expertise are Partial Familial Epilepsy, Spinocerebellar Ataxia Type 3, Spinocerebellar Ataxia, Spastic Paraplegia Type 4, and Intrauterine Device Insertion.
Antonio Orlacchio practices in Rome, Italy. Mr. Orlacchio is rated as an Elite expert by MediFind in the treatment of Spastic Paraplegia Type 4. His top areas of expertise are Spastic Paraplegia Type 7, Spastic Paraplegia Type 4, Paraplegia, Liver Transplant, and Cardiac Ablation.
Summary: Hereditary spastic paraplegia type 4 is the most frequent mutation of hereditary spastic paraplegias. It is commonly described as pure, with progressive weakness of the lower limbs, pyramidal syndrome and vesico-sphincter disorders. However, cognitive disorders have been reported for over 20 years, but remain poorly characterized.
Summary: Study goals 1. Prospective longitudinal data on progression in the natural course of SPG4 in presymptomatic mutation carriers prior to clinical disease onset and in early stages of disease 2. Biomarkers providing objective measures of disease activity
Published Date: July 01, 2020
Published By: National Institutes of Health