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Hereditary spastic paraplegia (HSP) is a group of
inherited disease A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosome abnormality. Although polygenic disorders are ...
s whose main feature is a progressive gait disorder. The disease presents with progressive stiffness (
spasticity Spasticity () is a feature of altered skeletal muscle performance with a combination of paralysis, increased tendon reflex activity, and hypertonia. It is also colloquially referred to as an unusual "tightness", stiffness, or "pull" of muscles. ...
) and contraction in the lower limbs. HSP is also known as hereditary spastic paraparesis, familial spastic paraplegia, French settlement disease, Strumpell disease, or Strumpell-Lorrain disease. The symptoms are a result of dysfunction of long
axon An axon (from Greek ἄξων ''áxōn'', axis) or nerve fiber (or nerve fibre: see American and British English spelling differences#-re, -er, spelling differences) is a long, slender cellular extensions, projection of a nerve cell, or neuron, ...
s in the
spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue that extends from the medulla oblongata in the lower brainstem to the lumbar region of the vertebral column (backbone) of vertebrate animals. The center of the spinal c ...
. The affected cells are the primary
motor neuron A motor neuron (or motoneuron), also known as efferent neuron is a neuron whose cell body is located in the motor cortex, brainstem or the spinal cord, and whose axon (fiber) projects to the spinal cord or outside of the spinal cord to directly o ...
s; therefore, the disease is an
upper motor neuron Upper motor neurons (UMNs) is a term introduced by William Gowers in 1886. They are found in the cerebral cortex and brainstem and carry information down to activate interneurons and lower motor neurons, which in turn directly signal muscles ...
disease. HSP is not a form of
cerebral palsy Cerebral palsy (CP) is a group of movement disorders that appear in early childhood. Signs and symptoms vary among people and over time, but include poor coordination, spasticity, stiff muscles, Paresis, weak muscles, and tremors. There may b ...
even though it physically may appear and behave much the same as
spastic diplegia Spastic diplegia is a form of cerebral palsy (CP) that primarily affects the legs, with possible considerable asymmetry between the two sides. It is a chronic neuromuscular condition of hypertonia and spasticity in the muscles of the lower e ...
. The origin of HSP is different from cerebral palsy. Despite this, some of the same anti-spasticity medications used in spastic cerebral palsy are sometimes used to treat HSP symptoms. HSP is caused by defects in transport of proteins, structural proteins, cell-maintaining proteins, lipids, and other substances through the cell. Long nerve fibers (axons) are affected because long distances make nerve cells particularly sensitive to defects in these mentioned mechanisms. The disease was first described in 1880 by the German neurologist
Adolph Strümpell Adolf (also spelt Adolph or Adolphe, Adolfo, and when Latinised Adolphus) is a given name with German origins. The name is a compound derived from the Old High German ''Athalwolf'' (or ''Hadulf''), a composition of ''athal'', or ''adal'', mea ...
. It was described more extensively in 1888 by Maurice Lorrain, a French physician. Due to their contribution in describing the disease, it is still called Strümpell-Lorrain disease in French-speaking countries. The term ''hereditary spastic paraplegia'' was coined by Anita Harding in 1983.


Signs and symptoms

Symptoms depend on the type of HSP inherited. The main feature of the disease is progressive
spasticity Spasticity () is a feature of altered skeletal muscle performance with a combination of paralysis, increased tendon reflex activity, and hypertonia. It is also colloquially referred to as an unusual "tightness", stiffness, or "pull" of muscles. ...
in the lower limbs due to
pyramidal tract The pyramidal tracts include both the corticobulbar tract and the corticospinal tract. These are aggregations of efferent nerve fibers from the upper motor neurons that travel from the cerebral cortex and terminate either in the brainstem (''cort ...
dysfunction. This also results in brisk reflexes, extensor plantar reflexes, muscle weakness, and variable bladder disturbances. Furthermore, among the core symptoms of HSP are also included abnormal gait and difficulty in walking, decreased vibratory sense at the ankles, and
paresthesia Paresthesia is a sensation of the skin that may feel like numbness (''hypoesthesia''), tingling, pricking, chilling, or burning. It can be temporary or Chronic condition, chronic and has many possible underlying causes. Paresthesia is usually p ...
. Individuals with HSP can experience extreme fatigue associated with central nervous system and neuromuscular disorders, which can be disabling. Initial symptoms are typically difficulty with balance, stubbing the toe or stumbling. Symptoms of HSP may begin at any age, from infancy to older than 60 years. If symptoms begin during the teenage years or later, then spastic gait disturbance usually progresses over many years. Canes, walkers, and wheelchairs may eventually be required, although some people never require assistance devices. Disability has been described as progressing more rapidly in adult onset forms. More specifically, patients with the autosomal dominant pure form of HSP reveal normal facial and extraocular movement. Although jaw jerk may be brisk in older subjects, there is no speech disturbance or difficulty of swallowing. Upper extremity muscle tone and strength are normal. In the lower extremities, muscle tone is increased at the hamstrings, quadriceps and ankles. Weakness is most notable at the
iliopsoas The iliopsoas muscle (; ) refers to the joined psoas major and the iliacus muscles. The two muscles are separate in the abdomen, but usually merge in the thigh. They are usually given the common name ''iliopsoas''. The iliopsoas muscle joins t ...
,
tibialis anterior The tibialis anterior muscle is a muscle of the anterior compartment of the lower leg. It originates from the upper portion of the tibia; it inserts into the medial cuneiform and first metatarsal bones of the foot. It acts to dorsiflex and invert ...
, and to a lesser extent,
hamstring A hamstring () is any one of the three posterior thigh muscles in human anatomy between the hip and the knee: from medial to lateral, the semimembranosus, semitendinosus and biceps femoris. Etymology The word " ham" is derived from the Old ...
muscles. In the complex form of the disorder, additional symptoms are present. These include: peripheral
neuropathy Peripheral neuropathy, often shortened to neuropathy, refers to damage or disease affecting the nerves. Damage to nerves may impair sensation, movement, gland function, and/or organ function depending on which nerve fibers are affected. Neuropa ...
, amyotrophy,
ataxia Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in e ...
,
intellectual disability Intellectual disability (ID), also known as general learning disability (in the United Kingdom), and formerly mental retardation (in the United States), Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010).Archive is a generalized neurodevelopmental ...
,
ichthyosis Ichthyosis is a family of genetic disorder, genetic skin disorders characterized by Xeroderma, dry, Scleroderma, thickened, scaly skin. The more than 20 types of ichthyosis range in severity of symptoms, outward appearance, underlying genetic cau ...
,
epilepsy Epilepsy is a group of Non-communicable disease, non-communicable Neurological disorder, neurological disorders characterized by a tendency for recurrent, unprovoked Seizure, seizures. A seizure is a sudden burst of abnormal electrical activit ...
, optic
neuropathy Peripheral neuropathy, often shortened to neuropathy, refers to damage or disease affecting the nerves. Damage to nerves may impair sensation, movement, gland function, and/or organ function depending on which nerve fibers are affected. Neuropa ...
,
dementia Dementia is a syndrome associated with many neurodegenerative diseases, characterized by a general decline in cognitive abilities that affects a person's ability to perform activities of daily living, everyday activities. This typically invo ...
,
deafness Deafness has varying definitions in cultural and medical contexts. In medical contexts, the meaning of deafness is hearing loss that precludes a person from understanding spoken language, an audiological condition. In this context it is writte ...
, or problems with speech, swallowing or breathing. Anita Harding classified the HSP in a pure and complicated form. Pure HSP presents with
spasticity Spasticity () is a feature of altered skeletal muscle performance with a combination of paralysis, increased tendon reflex activity, and hypertonia. It is also colloquially referred to as an unusual "tightness", stiffness, or "pull" of muscles. ...
in the lower limbs, associated with neurogenic bladder disturbance as well as lack of vibration sensitivity ( pallhypesthesia). On the other hand, HSP is classified as complex when lower limb spasticity is combined with any additional neurological symptom. This classification is subjective and patients with complex HSPs are sometimes diagnosed as having cerebellar ataxia with spasticity, intellectual disability (with spasticity), or
leukodystrophy Leukodystrophies are a group of, usually, inherited disorders, characterized by degeneration of the white matter in the brain. The word ''leukodystrophy'' comes from the Greek roots ''leuko'', "white", ''dys'', "abnormal" and ''troph'', "growth". ...
. Some of the genes listed below have been described in other diseases than HSP before. Therefore, some key genes overlap with other disease groups.


Age of onset

In the past, HSP has been classified as early onset beginning in early childhood or later onset in adulthood. The age of onsets has two points of maximum at age 2 and around age 40. New findings propose that an earlier onset leads to a longer disease duration without loss of ambulation or the need for the use of a wheelchair. This was also described earlier, that later onset forms evolve more rapidly. However, this is not always the case as De Novo Early Onset SPG4, a form of infantile HSP, involves loss of ambulation and other motor skills.


Cause

HSP is a group of genetic disorders. It follows general
inheritance Inheritance is the practice of receiving private property, titles, debts, entitlements, privileges, rights, and obligations upon the death of an individual. The rules of inheritance differ among societies and have changed over time. Offi ...
rules and can be inherited in an
autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...
,
autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...
or
X-linked recessive ''Main Article'': Sex linkage X-linked recessive inheritance is a mode of Mendelian inheritance, inheritance in which a mutation in a gene on the X chromosome causes the phenotype to be always expressed in males (who are necessarily hemizygous for ...
manner. The mode of inheritance involved has a direct impact on the chances of inheriting the disorder. Over 70 genotypes had been described, and over 50 genetic loci have been linked to this condition.Schüle R, Schöls L (2011) Genetics of hereditary spastic paraplegias. Semin Neurol 31(5):484-493 Ten genes have been identified with autosomal dominant inheritance. One of these, SPG4, accounts for ~50% of all genetically solved cases, or approximately 25% of all HSP cases. Twelve genes are known to be inherited in an autosomal recessive fashion. Collectively this latter group account for ~1/3 cases. Most altered genes have known function, but for some the function haven't been identified yet. All of them are listed in the gene list below, including their mode of inheritance. Some examples are spastin (SPG4) and paraplegin (SPG7) are both AAA ATPases.Wang YG, Shen L (2009) AAA ATPases and hereditary spastic paraplegia. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 26(3):298-301


Genotypes

The genes are designated ''SPG'' (Spastic gait gene). The gene locations are in the format: chromosome - arm (short or ''p'': long or ''q'') - band number. These designations are for the human genes only. The locations may (and probably will) vary in other organisms. Despite the number of genes known to be involved in this condition ~40% of cases have yet to have their cause identified.Helbig KL, Hedrich UB, Shinde DN, Krey I, Teichmann AC, Hentschel J, Schubert J, Chamberlin AC, Huether R, Lu HM4, Alcaraz WA, Tang S, Jungbluth C, Dugan SL, Vainionpää L, Karle KN, Synofzik M, Schöls L, Schüle R, Lehesjoki AE, Helbig I, Lerche H, Lemke JR (2016) A recurrent mutation in KCNA2 as a novel cause of hereditary spastic paraplegia and ataxia. Ann Neurol 80(4) In the table below ''SPG?'' is used to indicate a gene that has been associated with HSP but has not yet received an official HSP gene designation.


Pathophysiology

The major feature of HSP is a length-dependent axonal degeneration. These include the crossed and uncrossed
corticospinal tract The corticospinal tract is a white matter motor pathway starting at the cerebral cortex that terminates on lower motor neurons and interneurons in the spinal cord, controlling movements of the limbs and trunk. There are more than one million neu ...
s to the legs and
fasciculus gracilis ''Fasciculus vesanus'' is an extinct species of stem group, stem-group Ctenophora, ctenophores known from the Burgess Shale of British Columbia, Canada. It is dated to and belongs to middle Cambrian strata. The species is remarkable for its tw ...
. The
spinocerebellar tract The spinocerebellar tracts are nerve tracts originating in the spinal cord and terminating in the same side (ipsilateral) of the cerebellum. The two main tracts are the dorsal spinocerebellar tract, and the ventral spinocerebellar tract. Both of ...
is involved to a lesser extent. Neuronal cell bodies of degenerating axons are preserved and there is no evidence of primary
demyelination A demyelinating disease refers to any disease affecting the nervous system where the myelin sheath surrounding neurons is damaged. This damage disrupts the transmission of signals through the affected nerves, resulting in a decrease in their con ...
. Loss of anterior horn cells of the spinal cord are observed in some cases. Dorsal root ganglia, posterior roots and peripheral nerves are not directly affected. HSP affects several pathways in motor neurons. Many genes were identified and linked to HSP. It remains a challenge to accurately define the key players in each of the affected pathways, mainly because many genes have multiple functions and are involved in more than one pathway .


Axon pathfinding

Pathfinding is important for axon growth to the right destination (e.g. another nerve cell or a muscle). Significant for this mechanism is the L1CAM gene, a cell surface glycoprotein of the immunoglobulin superfamily. Mutations leading to a loss-of-function in L1CAM are also found in other X-linked syndromes. All of these disorders display corticospinal tract impairment (a hallmark feature of HSP). L1CAM participates in a set of interactions, binding other L1CAM molecules as well as extracellular cell adhesion molecules, integrins, and proteoglycans or intracellular proteins like ankyrins. The pathfinding defect occurs via the association of L1CAM with
neuropilin-1 Neuropilin-1 is a protein that in humans is encoded by the ''NRP1'' gene. In humans, the neuropilin 1 gene is located at 10p11.22. This is one of two human neuropilins. Function NRP1 is a membrane-bound coreceptor to a tyrosine kinase recep ...
. Neuropilin-1 interacts with Plexin-A proteins to form the Semaphorin-3A receptor complex. Semaphorin-a3A is then released in the ventral spinal cord to steer corticospinal neurons away from the midline spinal cord / medullary junction. If L1CAM does not work correctly due to a mutation, the cortiocospinal neurons are not directed to the correct position and the impairment occurs.


Lipid metabolism

Axons in the central and peripheral nervous system are coated with an insulation, the myelin layer, to increase the speed of action potential propagation. Abnormal myelination in the CNS is detected in some forms of hsp HSP.Noreau, A., Dion, P.A. & Rouleau, G.A., 2014. Molecular aspects of hereditary spastic paraplegia. Experimental Cell Research, 325(1), pp.18–26 Several genes were linked to myelin malformation, namely PLP1, GFC2 and FA2H. The mutations alter myelin composition, thickness and integrity. Endoplasmic reticulum (ER) is the main organelle for lipid synthesis. Mutations in genes encoding proteins that have a role in shaping ER morphology and lipid metabolism were linked to HSP. Mutations in ATL1, BSCL2 and
ERLIN2 Erlin-2 is a protein that in humans is encoded by the ''ERLIN2'' gene. References Further reading

* * * * {{gene-8-stub ...
alter ER structure, specifically the tubular network and the formation of three-way junctions in ER tubules. Many mutated genes are linked to abnormal lipid metabolism. The most prevalent effect is on arachidonic acid (
CYP2U1 CYP2U1 (cytochrome P450, family 2, subfamily U, polypeptide 1) is a protein that in humans is encoded by the ''CYP2U1'' gene Function This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are m ...
) and cholesterol ( CYP7B1) metabolism, phospholipase activity (DDHD1 and DDHD2), ganglioside formation ( B4GALNT-1) and the balance between carbohydrate and fat metabolism (SLV33A1).


Endosomal trafficking

Neurons take in substances from their surrounding by endocytosis. Endocytic vesicles fuse to endosomes in order to release their content. There are three main compartments that have endosome trafficking: Golgi to/from endosomes; plasma membrane to/from early endosomes (via recycling endosomes) and late endosomes to lysosomes. Dysfunction of endosomal trafficking can have severe consequences in motor neurons with long axons, as reported in HSP. Mutations in
AP4B1 AP-4 complex subunit beta-1 is a protein that in humans is encoded by the ''AP4B1'' gene. Function The heterotetrameric adaptor protein (AP) complexes sort integral membrane proteins at various stages of the endocytic and secretory pathways. A ...
and KIAA0415 are linked to disturbance in vesicle formation and membrane trafficking including selective uptake of proteins into vesicles. Both genes encode proteins that interact with several other proteins and disrupt the secretory and endocytic pathways.


Mitochondrial function

Mitochondrial dysfunctions have been connected with developmental and degenerative neurological disorders. Only a few HSP genes encode mitochondrial proteins. Two mitochondrial resident proteins are mutated in HSP: paraplegin and chaperonin 60. Paraplegin is a m-AAA metalloprotease of the inner mitochondrial membrane. It functions in ribosomal assembly and protein quality control. The impaired chaperonin 60 activity leads to impaired mitochondrial quality control. Two genes DDHD1 and
CYP2U1 CYP2U1 (cytochrome P450, family 2, subfamily U, polypeptide 1) is a protein that in humans is encoded by the ''CYP2U1'' gene Function This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are m ...
have shown alteration of mitochondrial architecture in patient fibroblasts. These genes encode enzymes involved in fatty-acid metabolism.


Diagnosis

Initial diagnosis of HSPs relies upon family history, the presence or absence of additional signs and the exclusion of other nongenetic causes of spasticity, the latter being particular important in sporadic cases. Cerebral and spinal
MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and rad ...
is an important procedure performed in order to rule out other frequent neurological conditions, such as
multiple sclerosis Multiple sclerosis (MS) is an autoimmune disease resulting in damage to myelinthe insulating covers of nerve cellsin the brain and spinal cord. As a demyelinating disease, MS disrupts the nervous system's ability to Action potential, transmit ...
, but also to detect associated abnormalities such as cerebellar or
corpus callosum The corpus callosum (Latin for "tough body"), also callosal commissure, is a wide, thick nerve tract, consisting of a flat bundle of commissural fibers, beneath the cerebral cortex in the brain. The corpus callosum is only found in placental ...
atrophy as well as
white matter White matter refers to areas of the central nervous system that are mainly made up of myelinated axons, also called Nerve tract, tracts. Long thought to be passive tissue, white matter affects learning and brain functions, modulating the distr ...
abnormalities.
Differential diagnosis In healthcare, a differential diagnosis (DDx) is a method of analysis that distinguishes a particular disease or condition from others that present with similar clinical features. Differential diagnostic procedures are used by clinicians to di ...
of HSP should also exclude
spastic diplegia Spastic diplegia is a form of cerebral palsy (CP) that primarily affects the legs, with possible considerable asymmetry between the two sides. It is a chronic neuromuscular condition of hypertonia and spasticity in the muscles of the lower e ...
which presents with nearly identical day-to-day effects and even is treatable with similar medicines such as
baclofen Baclofen, sold under the brand name Lioresal among others, is a medication used to treat muscle spasticity, such as from a spinal cord injury or multiple sclerosis. It may also be used for hiccups and muscle spasms near the end of life, and ...
and
orthopedic surgery Orthopedic surgery or orthopedics ( alternative spelling orthopaedics) is the branch of surgery concerned with conditions involving the musculoskeletal system. Orthopedic surgeons use both surgical and nonsurgical means to treat musculoskeletal ...
; at times, these two conditions may look and feel so similar that the only ''perceived'' difference may be HSP's hereditary nature versus the explicitly non-hereditary nature of spastic diplegia (however, unlike spastic diplegia and other forms of spastic cerebral palsy, HSP cannot be reliably treated with selective dorsal rhizotomy). Ultimate confirmation of HSP diagnosis can only be provided by carrying out
genetic test Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...
s targeted towards known genetic
mutations In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosi ...
.


Classification

Hereditary spastic paraplegias can be classified based on the symptoms; mode of inheritance; the patient's age at onset; the affected genes; and biochemical pathways involved.


Treatment

No specific treatment is known that would prevent, slow, or reverse HSP. Available therapies mainly consist of symptomatic medical management and promoting physical and emotional well-being. Therapeutics offered to HSP patients include: *
Baclofen Baclofen, sold under the brand name Lioresal among others, is a medication used to treat muscle spasticity, such as from a spinal cord injury or multiple sclerosis. It may also be used for hiccups and muscle spasms near the end of life, and ...
– a voluntary muscle relaxant to relax muscles and reduce tone. This can be administered orally or intrathecally. (Studies in HSP ) *
Tizanidine Tizanidine, sold under the brand name Zanaflex among others, is an alpha-2 (α2) adrenergic receptor agonist, similar to clonidine, that is used to treat muscle spasticity due to spinal cord injury, multiple sclerosis, and spastic cerebral ...
– to treat nocturnal or intermittent
spasm A spasm is a sudden involuntary contraction of a muscle, a group of muscles, or a hollow organ, such as the bladder. A spasmodic muscle contraction may be caused by many medical conditions, including dystonia. Most commonly, it is a musc ...
s (studies available ) *
Diazepam Diazepam, sold under the brand name Valium among others, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is used to treat a range of conditions, including anxiety disorder, anxiety, seizures, alcohol withdrawal syndr ...
and
clonazepam Clonazepam, sold under the brand name Klonopin among others, is a benzodiazepine medication used to prevent and treat anxiety disorders, seizures, bipolar mania, agitation associated with psychosis, obsessive–compulsive disorder (OCD), and ...
– to decrease intensity of spasms *
Oxybutynin chloride Oxybutynin, sold under the brand name Ditropan among others, is an anticholinergic medication primarily used to treat overactive bladder. It is widely considered a first-line therapy for overactive bladder due to its well-studied side effect ...
– an involuntary muscle relaxant and spasmolytic agent, used to reduce spasticity of the bladder in patients with bladder control problems *
Tolterodine Tolterodine, sold under the brand name Detrol among others, is a medication used to treat frequent urination, urinary incontinence, or urinary urgency. Effects are seen within an hour. It is taken by mouth. Common side effects include head ...
tartrate – an involuntary muscle relaxant and spasmolytic agent, used to reduce spasticity of the bladder in patients with bladder control problems * Cro System – to reduce muscle overactivity (existing studies for spasticity ) *
Botulinum toxin Botulinum toxin, or botulinum neurotoxin (commonly called botox), is a neurotoxic protein produced by the bacterium ''Clostridium botulinum'' and related species. It prevents the release of the neurotransmitter acetylcholine from axon en ...
– to reduce muscle overactivity (existing studies for HSP patientsde Niet M, de Bot ST, van de Warrenburg BP, Weerdesteyn V, Geurts AC. Functional effects of botulinum toxin type-A treatment and subsequent stretching of spastic calf muscles: A study in patients with hereditary spastic paraplegia. Journal of rehabilitation medicine. 2015;47(2):147-53.) *
Antidepressants Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include dry mouth, weight gain, dizziness, headaches, akathisia, sexu ...
(such as selective serotonin re-uptake inhibitors, tricyclic antidepressants and monoamine oxidase inhibitors) – for patients experiencing clinical depression *
Physical therapy Physical therapy (PT), also known as physiotherapy, is a healthcare profession, as well as the care provided by physical therapists who promote, maintain, or restore health through patient education, physical intervention, disease preventio ...
– to restore and maintain the ability to move; to reduce muscle tone; to maintain or improve range of motion and mobility; to increase strength and coordination; to prevent complications, such as frozen joints, contractures, or bedsores.


Prognosis

Although HSP is a progressive condition, the prognosis for individuals with HSP varies greatly. It primarily affects the legs although there can be some upperbody involvement in some individuals. Some cases are seriously disabling whilst others leave people able to do most ordinary activities to an ordinary extent without needing adjustments. The majority of individuals with HSP have a normal
life expectancy Human life expectancy is a statistical measure of the estimate of the average remaining years of life at a given age. The most commonly used measure is ''life expectancy at birth'' (LEB, or in demographic notation ''e''0, where '' ...
.


Epidemiology

Worldwide, the prevalence of all hereditary spastic paraplegias combined is estimated to be 2 to 6 in 100,000 people. A Norwegian study of more than 2.5 million people published in March 2009 has found an HSP prevalence rate of 7.4/100,000 of population – a higher rate, but in the same range as previous studies. No differences in rate relating to gender were found, and average age at onset was 24 years. In the
United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...
, Hereditary Spastic Paraplegia is listed as a "rare disease" by the Office of Rare Diseases (ORD) of the
National Institutes of Health The National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. It was founded in 1887 and is part of the United States Department of Health and Human Service ...
which means that the disorder affects less than 200,000 people in the US population.


References


Further reading


GeneReviews/NCBI/NIH/UW entry on Spastic Paraplegia 3A

GeneReviews/NCBI/NIH/UW entry on Hereditary Spastic Paraplegia Overview
*


External links


Spastic Paraplegia Foundation
{{DEFAULTSORT:Hereditary Spastic Paraplegia Systemic atrophies primarily affecting the central nervous system Genetic disorders with no OMIM Cytoskeletal defects Rare diseases