Hereditary Spastic Paraplegia (HSP): Facts and Information
Author: Thomas C. Weiss : Contact: Disabled World
Published: 2010-04-15 : (Rev. 2017-06-26)
Synopsis and Key Points:
Hereditary spastic paraplegia (HSP) a degenerative genetic disorder with stiffness and weakness of leg and hip muscles gait difficulties and issues with walking.
HSP is mainly characterized by different degrees of stiffness and weakness of the person's leg muscles and hip muscles, along with gait difficulties and issues with walking.
Hereditary spastic paraplegia (HSP), also known as hereditary spastic paraparesis, familial spastic paraplegias, French settlement disease, or Strumpell-Lorrain disease, is a group of inherited diseases whose main feature is progressive stiffness and contraction (spasticity) in the lower limbs, as a result of damage to or dysfunction of the nerves.
Hereditary spastic paraplegia (HSP) is a group of degenerative genetic disorders involving the spinal cord which are characterized by stiffness and progressive weakness of the affected person's legs. 'Spasticity,' is a term that refers to excessive muscle tone or muscle over-activity, with increased velocity-dependent resistance to stretch. The group of disorders is also known by some additional names, to include:
- Strumpell's disease
- Familial spastic paraplegia
- Familial spastic paraparesis
- Strumpell-Lorraine syndrome
- Hereditary spastic paraparesis
HSP is many times classified based upon whether progressive spasticity happens as an isolated finding, or whether it occurs in conjunction with additional neurological abnormalities. In families that are affected by complicated HSP, neurological features that are associated with the disorder have included deafness, degenerative changes to the person's retinas or the innermost membranes of their eyes, mental retardation, progressive deterioration of the person's thought processing, impaired coordination of the person's voluntary movements, and dementia.
As a form of genetic disorder, HSP can be inherited as an autosomal dominant, autosomal recessive, or x-linked recessive trait. The disorders can also be classified depending upon their modes of inheritance. Various subtypes may be determined by the location of the gene. Medical researchers have shown that HSP can be caused by mutations to a number of various genes, many of which have been mapped to specific chromosomes. The location of autosomal dominant, x-linked, and autosomal recessive HSP have been identified in a number of families affected by the disorders.
Causes of HSP
There is a rare form of infantile-onset ascending hereditary spastic paralysis (IAHSP) that is considered by some in the field of medical research to be a rare type of hereditary spastic paraplegia. Some people with IAHSP experience a deletion mutation in their ALS2 gene, located on the long arm of chromosome 2 at 2q33.2.
HSP can be transmitted as an autosomal dominant, autosomal reseccive, or x-linked recessive trait. It may be caused as a result of changes or mutations to several genes. A number of these genes have been mapped to specific locations on different chromosomes.
Uncomplicated HSP is the most common form of the disorder. Among the group of disorders, mutations of a number of genes seem to cause the symptoms and findings that people experience. Experts believe that nearly seventy-percent of people with uncomplicated HSP have it due to an autosomal dominant trait. Multiple genetic locations have been identified in various families with autosomal dominant HSP.
The majority of the families where the link has been established are associated with the SPG4 gene location on the short arm of chromosome 2. The evidence is suggestive that the SPG4 gene regulates production of a protein referred to as, 'spastin.' In members of specific families who have this form of HSP there can be reduced expression of the disorder. Due to this, some people who inherit a gene mutation for HSP might even be unaware of any symptoms that are associated with the disorder.
Medical science has also identified two x-linked forms of HSP. In one of these forms, the disorder seems to result from mutations in a gene that regulates production of the L1 cell adhesion molecule L1CAM. The gene has been mapped to chromosome Xq28. The other x-linked form of HSP that has been identified is believed to be caused by mutations in a gene that regulates production of a myelin protein referred to as, 'proteolipid protein (PLP).' The PLP gene is located on chromosome Xq22.
Genetic locations have also been identified in families who experience autosomal recessive HSP, to include chromosome 8 (SPG5A), 15q (SPG11), and 16q (SPG7). SPG7 has been associated with mutations of a gene which regulates the production of a protein referred to as, 'paraplegin.' Families have also been described by the medical community with autosomal recessive HSP, designated 'SPG5B' that might be the same as that referred to as, 'SPG7.'
Symptoms of HSP
HSP is mainly characterized by different degrees of stiffness and weakness of the person's leg muscles and hip muscles, along with gait difficulties and issues with walking. The onset of the disorder tends to be gradual, with the symptoms people experience commonly becoming progressively more severe over time. The person's age at the time of onset can vary greatly between families, as well as among affected family members. A number of people initially develop symptoms that start as early as infancy or early childhood, although symptoms may begin as late as the person's eighties or nineties. In some families, the symptoms of the disorder can appear at a progressively younger age with successive generations, something referred to as, 'genetic anticipation.' It is important to note; however, that this anticipation can result from an increase in awareness, as well as earlier detection of the disorder. The symptoms of HSP can include the following:
- Abnormal gait
- Delayed walking
- Repeated tripping or falling
- Weakness of the leg muscles
- Rigidity and increased tone of the person's leg muscles
People with uncomplicated HSP can also experience additional symptoms. These symptoms can include:
- Leg cramps
- Muscle spasms
- Highly arched feet
- Bladder control problems
- Relatively mild muscle wasting
- Diminished vibration sense in the feet
- Ankle clonus or abnormal reflex movements of the foot
While it is less common, families have been found in which progressive weakness and spasticity happens in association with other neurological features. When this occurs it is described as, 'complicated HSP.' In specific, isolated families, the following symptoms have included:
- Mental retardation
- Peripheral neuropathy
- Optic neuropathy
Families who experience complicated HSP can also have symptoms such as disturbances of the extra-pyramidal system, characterized by changes in muscle tone, postural abnormalities, impairments in the execution of voluntary actions, and/or the development of abnormal involuntary movements, ichthyosis or abnormal thickening, dryness, and scaling of the skin.
A diagnosis of HSP is commonly based on a careful history of the person and their family history, as well as a clinical evaluation and assessment of any characteristic symptoms the person is experiencing such as rigidity, weakness, gait disturbances, spasticity of their lower limbs, or diminished vibration sense in their feet. A diagnostic evaluation can also include a number of tests.
While DNA analysis of the person's blood samples can help in diagnosing particular forms of HSP, the testing itself is not something that is widely available. Due to the lack of availability, there is currently no definitive test for HSP. Instead, if the affected person has characteristic symptoms of the disorder, and their family members have had similar features, the findings suggest a potential diagnosis of HSP. A diagnostic evaluation can include specialized testing to help detect or characterize certain finding that may be associated with HSP. Studies can be conducted to assist in ruling out or detecting other disorders that present similar symptoms. Diagnostic studies that are recommended for people who are suspected of having HSP can include:
- Lumbar puncture
- Reflex studies to detect abnormal reflex responses
- Certain blood tests and additional laboratory studies
- Neuroimaging studies, including CT scanning or MRI
- Electro-physiologic studies, such as EMG, nerve conduction tests, or EEG
Treatment of HSP
Treatment of HSP consists of both symptomatic and supportive medical management, as well as additional supportive services such as physical therapy. While there is no specific form of treatment available that will slow down or otherwise alter the progression of HSP, therapy with baclofen can help to reduce spasticity in some people with HSP. Another skeletal muscle relaxant, dantrolen, can also improve spasticity in some people with the disorder. Additional medications that can provide some benefit to people with HSP include zanaflex, diazepam, or conazepam. For people with HSP who experience bladder control issues, treatment with oxybutynin might help to relieve bladder spasticity.
Some people with HSP might be candidates for, 'chemodenervation,' a therapeutic approach that can help to reduce muscle over-activity without systemic side-effects. As an example, some people benefit from injections of boulinum toxin type A into their hip adductors, or ankle plantar flexors. For others, injections of phenol into their obturator nerve can provide some benefit. In some people with slowly progressive disease, neuro-orthopedic surgery to lengthen their ankle plantar flexors or hip adductors might help.
Even though physical therapy does not either prevent or reduce degenerative changes to the person's spinal cord, it is believed that receiving regular therapy can play an important part in assisting people with HSP to maintain and increase their muscle strength, as well as improving their range of motion. In people with childhood onset HSP, early intervention with physical therapy can lead to an increase in their functional mobility and ambulation.
- The prevalence of HSP has been estimated to range from 1.3:100,000 (in Ireland) [McMonagle et al 2002], to 9.6: 100,000 (in Spain) [Sedel et al 2007].
- Genetic types of hereditary spastic paraplegia (HSP). To date, more than 56 HSP loci and 41HSP-related genes have been identified.
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