What are the other Names for this Condition? (Also known as/Synonyms)

• Familial Spastic Paraparesis (FSP)
• FSP (Familial Spastic Paraparesis)
• HSP (Hereditary Spastic Paraplegia)

What is Hereditary Spastic Paraplegia? (Definition/Background Information)

• Hereditary Spastic Paraplegia (HSP) is a group of hereditary, degenerative, neurological disorders that primarily affect the upper motor neurons
• Upper motor neurons in the brain and spinal cord deliver signals to the lower motor neurons, which in turn, carry messages to the muscles
• In Hereditary Spastic Paraplegia, upper motor neurons slowly degenerate so the muscles do not receive the correct messages, causing progressive spasticity (increased muscle tone/stiffness) and weakness of the legs. This leads to difficulty walking. As degeneration continues, symptoms worsen
• If only the lower body is affected, HSP is classified as uncomplicated or pure. HSP is classified as complicated or complex if other systems are involved. In these cases, additional symptoms, including impaired vision, ataxia, epilepsy, cognitive impairment, peripheral neuropathy, and/or deafness, occur
• The different forms of Hereditary Spastic Paraplegia are caused by mutations in different genes. The pattern of inheritance varies across the cases
• There are no specific treatments to prevent, slow, or reverse Hereditary Spastic Paraplegia. Individual symptoms may be treated with medications and/or physical therapy

(Source: Hereditary Spastic Paraplegia; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Hereditary Spastic Paraplegia? (Age and Sex Distribution)

• Hereditary Spastic Paraplegia is a rare congenital disorder. However, the presentation of symptoms are seen between the ages 10-40 years
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Hereditary Spastic Paraplegia? (Predisposing Factors)

• A positive family history may be an important risk factor, since Hereditary Spastic Paraplegia is an inherited condition
• Currently, no other risk factors have been clearly identified for HSP

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Hereditary Spastic Paraplegia? (Etiology)

• The different forms of Hereditary Spastic Paraplegia are caused by mutations in different genes. At this point, over 70 different types of HSP have been described
• The different patterns of inheritance are autosomal dominant, autosomal recessive, and X-linked recessive

(Source: Hereditary Spastic Paraplegia; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA)

Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

X-linked recessive conditions are traits or disorders that occur when two copies of an abnormal gene are inherited on a sex chromosome (X or Y chromosome). All X-linked recessive traits are fully evident in males, because they have only one copy of the X chromosome. This means that there is no normal gene present to mask the effects of the mutant copy. All males who are affected will pass the mutated gene onto their female offspring, because they must inherit one copy of the X chromosome from each parent. This means that they will be unaffected carriers. Females are rarely affected by X-linked recessive disorders because they have two copies of the X chromosome. In the rare case that they inherit two mutated copies of the gene, they will inherit the condition.

What are the Signs and Symptoms of Hereditary Spastic Paraplegia?

The hallmark feature of Hereditary Spastic Paraplegia is progressive weakness and spasticity (stiffness) of the legs. Symptoms typically develop between the second and fourth decades (although earlier and later presentation has been described). Early in the disease course, there may be mild gait difficulties and stiffness. These symptoms typically slowly progress so that eventually, individuals with HSP may require the assistance of a cane, walker, or wheelchair.

In some cases, additional symptoms may occur. These can include:

• Impaired vision
• Ataxia
• Urinary urgency and frequency
• Hyperactive reflexes
• Babinski's sign 
• Difficulty with balance
• Epilepsy 
• Cognitive impairment
• Peripheral neuropathy
• Deafness

Based on the frequency of symptoms observed, the following information may be noted:

• Very frequently present symptoms in 80-99% of the cases:
  • Gait disturbance
  • Impaired pain sensation
  • Paraplegia
  • Spasticity
• Frequently present symptoms in 30-79% of the cases: Ataxia
• Occasionally present symptoms in 5-29% of the cases: Finger syndactyly

(Source: Hereditary Spastic Paraplegia; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA)

How is Hereditary Spastic Paraplegia Diagnosed?

Hereditary Spastic Paraplegia is diagnosed on the basis of the following:

• Characteristic clinical symptoms of slowly progressive weakness and stiffness in the legs often accompanied by urinary urgency
• Neurologic examination demonstrating damage to the nerve paths connecting the spinal cord and the brain (corticospinal tract), such as spastic weakness, exaggerated reflexes, typically associated with bilateral extensor plantar responses; often accompanied by a mild inability to sense vibration in the lower part of the legs and muscle changes of the urinary bladder
• Family history shows a pattern of inheritance that is either autosomal dominant, autosomal recessive, or X-linked recessive
• Exclusion of other disorders that cause spasticity and weakness in the legs
• Identification of a disease-causing mutation in an HSP-causing gene; such testing is increasingly available and can confirm the diagnosis of HSP

(Source: Hereditary Spastic Paraplegia; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Hereditary Spastic Paraplegia?

The complications of Hereditary Spastic Paraplegia may include:

• Walking difficulties, immobility
• Reduced quality of daily life

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Hereditary Spastic Paraplegia Treated?

There are no specific treatments to prevent, slow, or reverse Hereditary Spastic Paraplegia.

• Treatment is symptomatic and supportive
• Medications may be considered for spasticity and urinary urgency
• Regular physical therapy is important for muscle strength and to preserve range of motion

(Source: Hereditary Spastic Paraplegia; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA)

How can Hereditary Spastic Paraplegia be Prevented?

Currently, Hereditary Spastic Paraplegia may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Hereditary Spastic Paraplegia? (Outcomes/Resolutions)

• The prognosis for individuals with Hereditary Spastic Paraplegia varies
• Some individuals are very disabled and others have only mild disability

The majority of individuals with uncomplicated HSP have a normal life expectancy.

(Source: Hereditary Spastic Paraplegia; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA)

Additional and Relevant Useful Information for Hereditary Spastic Paraplegia:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/