Hereditary spastic paraplegia is a general term for an expanding group of rare genetic disorders characterized by slowly progressive weakness (paraplegia) and increased muscle tone and stiffness (spasticity) of leg muscles. Other symptoms can occur in the pure subtypes including bladder dysfunction or abnormal sensations in the lower legs or feet. HSP is classified as “complex” or “complicated” if additional symptoms are present such as an inability to coordinate voluntary movements (ataxia), seizures, intellectual disability, skin disease, dementia, and hearing and vision abnormalities. Individual forms of HSP are caused by a mutation to a specific gene.
By definition all subtypes of HSP are characterized by spastic paraplegia. Below is a list of several of the better known subtypes of HSP. Next to the subtypes name is the inheritance pattern; whether it is pure, complex or both; genetic locus (location of the disease gene whether known or unknown): the gene name (if known): and a brief description of symptoms. Many of the subtypes of HSP have been identified have only been seen in individual families (kindreds) or only a few individuals; most of those disorders are not discussed here.
SPG1: X-linked – Complicated – Xp28 – L1CAM
This form of HSP affects males and is associated with developmental delays, moderate to severe intellectual disability, adducted thumbs, and hydrocephalus, a condition in which accumulation of excessive cerebrospinal fluid in the skull causes pressure on the tissues of the brain. The L1CAM gene mutation that causes SPG1 also causes MASA syndrome, X-linked corpus callosum agenesis, and X-linked hydrocephalus with stenosis of the aqueduct of Sylvius. Collectively, these disorders are known as L1 syndrome. NORD has a separate report on L1 syndrome.