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 while others are less disabling and are compatible with a productive and full life. The majority of individuals with HSP have a normal life expectancy.

HSP is a group of genetic disorders. It follows general inheritance rules and can be inherited in an autosomal dominant, autosomal recessive or X-linked recessive 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. Ten genes have been identified with autosomal dominant inheritance. One of these SPG4 accounts for ~50% of all genetically solved cases 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.

The prevalence of SCA6 varies by culture. In Germany, SCA6 accounts for 10-25% of all autosomal dominant cases of SCA (SCA itself having a prevalence of 1 in 100,000). This prevalence in lower in Japan, however, where SCA6 accounts for only ~6% of spinocerebellar ataxias. In Australia, SCA6 accounts for 30% of spinocerebellar ataxia cases while 11% in the Dutch.

The hereditary ataxias are categorized by mode of inheritance and causative gene or chromosomal locus. The hereditary ataxias can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner.

- Many types of autosomal dominant cerebellar ataxias for which specific genetic information is available are now known. Synonyms for autosomal-dominant cerebellar ataxias (ADCA) used prior to the current understanding of the molecular genetics were Marie's ataxia, inherited olivopontocerebellar atrophy, cerebello-olivary atrophy, or the more generic term "spinocerebellar degeneration." (Spinocerebellar degeneration is a rare inherited neurological disorder of the central nervous system characterized by the slow degeneration of certain areas of the brain. There are three forms of spinocerebellar degeneration: Types 1, 2, 3. Symptoms begin during adulthood.)

- There are five typical "autosomal-recessive" disorders in which ataxia is a prominent feature: Friedreich ataxia, ataxia-telangiectasia, ataxia with vitamin E deficiency, ataxia with oculomotor apraxia (AOA), spastic ataxia. Disorder subdivisions: Friedreich's ataxia, Spinocerebellar ataxia, Ataxia telangiectasia, Vasomotor ataxia, Vestibulocerebellar, Ataxiadynamia, Ataxiophemia, Olivopontocerebellar atrophy, and Charcot-Marie-Tooth disease.

- There have been reported cases where a polyglutamine expansion may lengthen when passed down, which often can result in an earlier age-of-onset and a more severe disease phenotype for individuals who inherit the disease allele. This falls under the category of genetic anticipation.

There is no known prevention of spinocerebellar ataxia. Those who are believed to be at risk can have genetic sequencing of known SCA loci performed to confirm inheritance of the disorder.

In terms of frequency, is estimated at 2 per 100,000, it has identified in different regions of the world. Some clusters of certain types of autosomal dominant cerebellar ataxia reach a prevalence of 5 per 100,000.

Spinocerebellar ataxia (SCA), also known as spinocerebellar atrophy or spinocerebellar degeneration, is a progressive, degenerative, genetic disease with multiple types, each of which could be considered a disease in its own right. An estimated 150,000 people in the United States have a diagnosis of spinocerebellar ataxia at any given time. SCA is hereditary, progressive, degenerative, and often fatal. There is no known effective treatment or cure. SCA can affect anyone of any age. The disease is caused by either a recessive or dominant gene. In many cases people are not aware that they carry a relevant gene until they have children who begin to show signs of having the disorder.

In most cases, between the age of 2 and 4 oculomotor signals are present. Between the age of 2 and 8, telangiectasias appears. Usually by the age of 10 the child needs a wheel chair. Individuals with autosomal recessive cerebellum ataxia usually survive till their 20s; in some cases individuals have survived till their 40s or 50s.

Olivopontocerebellar atrophy (OPCA) is the degeneration of neurons in specific areas of the brain – the cerebellum, pons, and inferior olives. OPCA is present in several neurodegenerative syndromes, including inherited and non-inherited forms of ataxia (such as the hereditary spinocerebellar ataxia known as Machado–Joseph disease) and multiple system atrophy (MSA), with which it is primarily associated.

OPCA may also be found in the brains of individuals with prion disorders and inherited metabolic diseases. The characteristic areas of brain damage that indicate OPCA can be seen by imaging the brain using CT scans or MRI studies.

The term was originally coined by Joseph Jules Dejerine and André Thomas.

Patients with severe forms of MJD have a life expectancy of approximately 35 years. Those with mild forms have a normal life expectancy. The cause of death of those who die early is often aspiration pneumonia.

Olivopontocerebellar atrophy is hereditary, but has an unknown genetic basis. There are two forms:

A few non-hereditary diseases formerly categorized as olivopontocerebellar atrophy have been reclassified as forms of multiple system atrophy as well as to four hereditary types, that have been currently reclassified as four different forms of spinocerebellar ataxia:

There is no known prevention of spinocerebellar ataxia. Those who are believed to be at risk can have genetic sequencing of known SCA loci performed to confirm inheritance of the disorder.

In some cases, spastic cerebral palsy is caused by genetic factors.

The genetic factors for spastic cerebral palsy include:

Although it has its origins in a brain injury, spastic CP can largely be thought of as a collection of orthopaedic and neuromuscular issues because of how it manifests symptomatically over the course of the person's lifespan. It is therefore not the same as "brain damage" and it need not be thought of as such. Spastic quadriplegia in particular, especially if it is combined with verbal speech challenges and strabismus, may be misinterpreted by the general population as alluding to cognitive dimensions to the disability atop the physical ones, but this is false; the intelligence of a person with any type of spastic CP is unaffected by the condition "of the spasticity itself".

In spastic cerebral palsy in children with low birth weights, 25% of children had hemiplegia, 37.5% had quadriplegia, and 37.5% had diplegia.

In terms of the genetics of autosomal dominant cerebellar ataxia 11 of 18 known genes are caused by repeated expansions in corresponding proteins, sharing the same mutational mechanism. SCAs can be caused by conventional mutations or large rearrangements in genes that make glutamate and calcium signaling, channel function, tau regulation and mitochondrial activity or RNA alteration.

The mechanism of Type I is not completely known, however Whaley, et al. suggest the polyglutamine product is toxic to the cell at a protein level, this effect may be done by transcriptional dysregulation and disruption of calcium homeostasis which causes apoptosis to occur earlier.

The incidence of dominant optic atrophy has been estimated to be 1:50000 with prevalence as high as 1:10000 in the Danish population (Votruba, 1998). Dominant optic atrophy is inherited in an autosomal dominant manner. That is, a heterozygous patient with the disease has a 50% chance of passing on the disease to offspring, assuming his/her partner does not have the disease. Males and females are affected at the same rate. Although Kjer's has a high penetrance (98%), severity and progression of DOA are extremely variable even within the same family.

Behr syndrome is characterized by the association of early-onset optic atrophy with spinocerebellar degeneration resulting in ataxia, pyramidal signs, peripheral neuropathy and developmental delay.

Although it is an autosomal recessive disorder, heterozygotes may still manifest much attenuated symptoms. Autosomal dominant inheritance also being reported in a family. Recently a variant of OPA1 mutation with phenotypic presentation like Behr syndrome is also described. Some reported cases have been found to carry mutations in the OPA1, OPA3 or C12ORF65 genes which are known causes of pure optic atrophy or optic atrophy complicated by movement disorder.

Ataxia with telangiectasia is a rare form ataxia that causes chromosomal instability, sensitivity to ionizing radiation, disrupted stress-activated signal transduction pathways and radioresistant DNA synthesis.

The genes that underlie majority of the symptoms for the different types of ataxia are still unknown. A productive cure is still unavailable to prevent the brain degeneration associated with ataxia.

Oculomotor ataxia accompanies gait ataxia which causes dysarthria, muscle weakness, loss of joint position sense and limb dysmetria. In some cases, patients have shown mental retardation and loss of myelinated axons.

An average clinical profile from published studies shows that the median onset age for HDLS patients is 44.3 years with a mean disease duration of 5.8 years and mean age of death at 53.2 years. As of 2012, there have been around 15 cases identified with at least 11 sporadic cases of HDLS. HDLS cases have been located in Germany, Norway, Sweden, and the United States, showing an international distribution focusing between Northern Europe and the United States.

Through the study of numerous kindred, it was found that the disease did not occur among just males or females, but rather was evenly distributed indicative of an autosomal rather than a sex-linked genetic disorder. It was also observed that the HDLS cases did not skip generations as it would occur with a recessive inheritance, and as such has been labeled autosomal dominant.

Dominant optic atrophy is also known as autosomal dominant optic atrophy, Kjer type; Kjer optic atrophy; or, Kjer's autosomal dominant optic atrophy.

The muscle spasticity can cause gait patterns to be awkward and jerky. The constant spastic state of the muscle can lead to bone and tendon deformation, further complicating the patient's mobility. Many patients with spastic hemiplegia are subjected to canes, walkers and even wheelchairs. Due to the decrease in weight bearing, patients are at a higher risk of developing osteoporosis. An unhealthy weight can further complicate mobility. Patients with spastic hemiplegia are a high risk for experiencing seizures. Oromotor dysfunction puts patients at risk for aspiration pneumonia. Visual field deficits can cause impaired two-point discrimination. Many patients experience the loss of sensation in the arms and legs on the affected side of the body. Nutrition is essential for the proper growth and development for a child with spastic hemiplegia.

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a rare adult onset autosomal dominant disorder characterized by cerebral white matter degeneration with demyelination and axonal spheroids leading to progressive cognitive and motor dysfunction. Spheroids are axonal swellings with discontinuous or absence of myelin sheaths. It is believed that the disease arises from primary microglial dysfunction that leads to secondary disruption of axonal integrity, neuroaxonal damage, and focal axonal spheroids leading to demyelination. Spheroids in HDLS resemble to some extent those produced by shear stress in a closed head injury with damage to axons, causing them to swell due to blockage of axoplasmic transport. In addition to trauma, axonal spheroids can be found in aged brain, stroke, and in other degenerative diseases. In HDLS, it is uncertain whether demyelination occurs prior to the axonal spheroids or what triggers neurodegeneration after apparently normal brain and white matter development, although genetic deficits suggest that demyelination and axonal pathology may be secondary to microglial dysfunction. The clinical syndrome in patients with HDLS is not specific and it can be mistaken for Alzheimer's disease, frontotemporal dementia, atypical Parkinsonism, multiple sclerosis, or corticobasal degeneration.

Spastic diplegia's particular type of brain damage inhibits the proper development of upper motor neuron function, impacting the motor cortex, the basal ganglia and the corticospinal tract. Nerve receptors in the spine leading to affected muscles become unable to properly absorb gamma amino butyric acid (GABA), the amino acid that regulates muscle tone in humans. Without GABA absorption to those particular nerve rootlets (usually centred, in this case, around the sectors L1-S1 and L2-S2), affected nerves (here, the ones controlling the legs) perpetually fire the message for their corresponding muscles to permanently, rigidly contract, and the muscles become permanently hypertonic (spastic).

The abnormally high muscle tone that results creates lifelong difficulty with all voluntary and passive movement in the legs, and in general creates stress over time—depending on the severity of the condition in the individual, the constant spasticity ultimately produces pain, muscle/joint breakdown including tendinitis and arthritis, premature physical exhaustion (i.e., becoming physically exhausted even when you internally know that you have more energy than you are able to use), contractures, spasms, and progressively worse deformities/mis-alignments of bone structure around areas of the tightened musculature as the person's years progress. Severe arthritis, tendinitis, and similar breakdown can start as early as the spastic diplegic person's mid-20s (as a comparison, typical people with normal muscle tone are not at risk of arthritis, tendinitis, and similar breakdown until well into their 50s or 60s, if even then).

No type of CP is officially a progressive condition, and indeed spastic diplegia does not clinically "get worse" given the nerves, damaged permanently at birth, neither recover nor degrade. This aspect is clinically significant because other neuromuscular conditions with similar surface characteristics in their presentations, like most forms of multiple sclerosis, indeed do degrade the body over time and do involve actual progressive worsening of the condition, including the spasticity often seen in MS. However, spastic diplegia is indeed a chronic condition; the symptoms themselves cause compounded effects on the body that are typically just as stressful on the human body as a progressive condition is. Despite this reality and the fact that muscle tightness is the symptom of spastic diplegia and not the cause, symptoms rather than cause are typically seen as the primary area of focus for treatment, especially surgical treatment, except when a selective dorsal rhizotomy is brought into consideration, or when an oral baclofen regimen is attempted.

Unlike any other condition that may present with similar effects, spastic diplegia is entirely congenital in origin—that is, it is almost always acquired shortly before or during a baby's birth process. Things like exposure to toxins, traumatic brain injury, encephalitis, meningitis, drowning, or suffocation do not tend to lead to spastic diplegia in particular or even cerebral palsy generally. Overall, the most common cause of spastic diplegia is Periventricular leukomalacia, more commonly known as neonatal asphyxia or infant hypoxia—a sudden in-womb shortage of oxygen-delivery through the umbilical cord. This sudden lack of oxygen is also almost always combined with premature birth, a phenomenon that, even by itself, would inherently risk the infant developing some type of CP. On the other hand, the presence of certain maternal infections during pregnancy such as congenital rubella syndrome can also lead to spastic diplegia, since such infections can have similar end results to infant hypoxia.

The prognosis for those with spastic muscles depends on multiple factors, including the severity of the spasticity and the associated movement disorder, access to specialised and intensive management, and ability of the affected individual to maintain the management plan (particularly an exercise program). Most people with a significant UMN lesion will have ongoing impairment, but most of these will be able to make progress. The most important factor to indicate ability to progress is seeing improvement, but improvement in many spastic movement disorders may not be seen until the affected individual receives help from a specialised team or health professional.

The prognosis for Tropical spastic paraparesis indicates some improvement in a percentage of cases due to immunosuppressive treatment. A higher percentage will eventually lose the ability to walk within a ten-year interval.

In the industrialized world, the incidence of overall cerebral palsy, which includes but is not limited to spastic diplegia, is about 2 per 1000 live births. Thus far, there is no known study recording the incidence of CP in the overall nonindustrialized world. Therefore, it is safe to assume that not all spastic CP individuals are known to science and medicine, especially in areas of the world where healthcare systems are less advanced. Many such individuals may simply live out their lives in their local communities without any medical or orthopedic oversight at all, or with extremely minimal such treatment, so that they are never able to be incorporated into any empirical data that orthopedic surgeons or neurosurgeons might seek to collect. It is shocking to note that—as with people with physical disability overall—some may even find themselves in situations of institutionalization, and thus barely see the outside world at all.

From what "is" known, the incidence of spastic diplegia is higher in males than in females; the Surveillance of Cerebral Palsy in Europe (SCPE), for example, reports a M:F ratio of 1.33:1. Variances in reported rates of incidence across different geographical areas in industrialized countries are thought to be caused primarily by discrepancies in the criteria used for inclusion and exclusion.

When such discrepancies are taken into account in comparing two or more registers of patients with cerebral palsy and also the extent to which children with mild cerebral palsy are included, the incidence rates still converge toward the average rate of 2:1000.

In the United States, approximately 10,000 infants and babies are born with CP each year, and 1200–1500 are diagnosed at preschool age when symptoms become more obvious. It is interesting to note that those with extremely mild spastic CP may not even be aware of their condition until much later in life: Internet chat forums have recorded men and women as old as 30 who were diagnosed only recently with their spastic CP.

Overall, advances in care of pregnant mothers and their babies has not resulted in a noticeable decrease in CP; in fact, because medical advances in areas related to the care of premature babies has resulted in a greater survival rate in recent years, it is actually "more" likely for infants with cerebral palsy to be born into the world now than it would have been in the past. Only the introduction of quality medical care to locations with less-than-adequate medical care has shown any decreases in the incidences of CP; the rest either have shown no change or have actually shown an increase. The incidence of CP increases with premature or very low-weight babies regardless of the quality of care.