What is HSP?

What is Hereditary Spastic Paraplegia?

Hereditary Spastic Paraplegia (HSP) is a broad group of inherited, degenerative disorders characterised by impaired walking due to spasticity and weakness of the legs. The primary features of HSP are spasticity and weakness with the proportions varying from individual to individual. Symptoms generally worsen over time, though by how much and how fast is highly variable. Diagnosis is primarily by clinical neurological examination and testing as there are similarities with a number of other disorders. Genetic testing for HSP is now widely available. The detection rate of HSP mutations is in the 50–60% range with state-of-the-art next-generation whole exome sequencing.

Also known as

Hereditary Spastic Paraplegia (HSP) is also called Familial Spastic Paraplegia or Paraparesis (FSP) and Strumpell-Lorraine Syndrome, as well as other less commonly used names including Spastic Paraplegia, Hereditary Charcot-Disease, Spastic Spinal Paralysis, Diplegia Spinalis Progressiva, French Settlement Disease, Troyer syndrome, and Silver syndrome. Hereditary Spastic Paraplegia is the most common name used in the USA, UK and Australia.


The disease has been reported in nearly every country.  Frequency estimates vary widely (from 0.5 to 12 people per 100,000 of population) and are an estimate or approximation as highly reliable data are not available.  Based on the most recent and largest study so far on prevalence, a rate of 7.4/100,000 of population has been estimated. No differences in rate relating to gender have been found in most population studies, however in at least one larger study, prevalence in males was found to be significantly higher. Average age of symptom onset is 24 years old. There is also juvenile onset HSP which can show up in children of any age and tends to be associated with more severe symptoms.

Extrapolated to the Australian population, this translates to about 1,700 HSPers, with over 500,000 globally. Every 3 weeks in Australia a child is born with an HSP mutation.

Being rare, it is a low profile disease globally, largely unknown in the general population, and receiving little medical research attention.

Worldwide, HSP is thought to be under-diagnosed as mild cases (which go undiagnosed) exist. Around 15% of people with HSP mutations, quoted in some places as high as 25%, never show symptoms. Misdiagnosis –  commonly as Multiple Sclerosis, Cerebral Palsy or Primary Lateral Sclerosis – is not uncommon, while some HSP diagnoses proved to be incorrect. Overall, total numbers with HSP are likely to be underestimated.


HSP is most commonly characterised by muscle stiffness, spasm and weakness in the legs. Most frequent onset is in early adulthood (2nd to 4th decade) but can be as late as the 50’s or even later for some.  A lesser onset peak is in children under 6 years old. Onset symptoms are commonly the occasional stumble, trip or fall while walking due to the foot ‘dragging’ somewhat and the toes catching.  An awkward gait also develops.  Some reflexes may become exaggerated and the arches of the feet may increase in height.

Whilst the HSP-associated genetic mutation occurring in any particular extended family is very highly likely to be exactly the same, what is known as phenotypic variation can be huge. Variation in the phenotype in a family may occur in factors such as:

  • age of onset – in the one family with the same mutation, it is not uncommon to have examples of early onset in infancy or the teens of mild symptoms and late onset in adults in their 40s, 50s or even older
  • symptom profile (gait features and characteristics; which muscles are weak and which muscles are spastic; the relativity of weakness vs spasticity overall for an individual – in some HSPers, muscle weakness is dominant, while in others spasticity is dominant; presence or absence of bladder and/or bowel continence issues, cognitive impairment, speech impairment, hearing impairment or abnormalities with the eyes)
  • rate of progression/degeneration.

Examples of HSP gait

Here are two video examples of HSP gait – the first shows members of the HSP community in Queensland, Australia who were videoed walking during a study investigating a new way to quantify mobility/movement. The second video is from Norway. The title roughly translates to ‘HSP movement patterns’.

Progression of the disease often results in the need for a cane or walker and more severe cases ultimately require a wheelchair.  A wide variety of symptoms are observed across cases and over time given the degenerative nature of the disease.  Now that so many gene mutations have been identified as causing HSP, it may explain some of the variation in both symptoms and severity between cases.  The majority of individuals with HSP have a normal life expectancy.

Less common symptoms include urinary urgency.  Even less commonly, the upper limbs and voice can be affected, particularly in severe, early onset cases.  In rare, ‘complicated’ forms it can be accompanied by other neurological symptoms including optic neuropathy and retinopathy (eye diseases), dementia, mental retardation, ataxia (lack of muscle control), icthyosis (skin disorder), peripheral neuropathy (commonly tingling or numbness in hands or feet) and deafness. Severe pain sometimes also occurs. Many other diseases can also possibly complicate the symptoms of HSP if present.


HSP is a genetic, inherited or hereditary disease – that is, it is passed on from generation to generation. It is caused by abnormal variations (mutations) in the genes that may be passed on from an affected parent to the unborn child in their DNA (genetic material).  As at 2016, more than 70 genes/loci have been separately implicated in causing HSP.  The number of genes so identified has increased from 9 in 2004, and many more discoveries are to be expected.  Multiple mutation locations and types have also been identified, with over 150 for the SPAST/SPG4 gene alone.  Any of these identified mutations can cause HSP.  Specifically, they cause the production of too much or too little of either the normal protein or another protein that causes nerve damage through degeneration of the corticospinal tracts.  The long nerves (axons) are prevented from doing their critical job of sending the right signals to control the muscles. HSP is classified as an upper motor neurone neurodegenerative disease.

Although most HSP is inherited from parents, this is not always the case. When a genetic disease occurs without any family history or genetic defects in the parents, the disease is called a “sporadic” genetic disease. The cause is usually a random gene mutation that occurred somewhere in the development of the unborn child. In this way, rare cases of HSP are possible even if neither parent has an HSP mutation. It is an explanation of how the disease occurred in the first place. In such cases, the risk of a reoccurrence in a second child is very low, but genetic testing is the only reliable way to check whether or not the parents have an HSP mutation, even if neither of them has any HSP symptoms.

Genes & Heredity

‘Autosomal dominant’ (AD) HSP is the predominant form of the disorder, accounting for over half of all cases.  It occurs when the child inherits the defective gene from a parent and this defective gene dominates the normal corresponding gene from the other parent.  The probability of hereditary transmission to the child if one parent has HSP is 50% for AD-HSP.

So, a dominant or strong defective gene will need only one copy to cause disease, but a weak defective gene will need two copies, one from each parent, to cause disease (known as recessive).

The term “carriers” is often used to describe people who have a single copy of a weak defective gene, and do not show any HSP symptoms.  If two parents who are both “carriers” have children, there is a chance that they will pass on the genetic defect to their children.  The combination of genes given to the child will decide whether the children are unaffected and have normal genes (25%), are carriers themselves (50%), or develop the disease (25%).  Only those children who inherit two copies of the weak, defective gene can develop the disease.  This type of inheritance is referred to as ‘autosomal recessive’ HSP (AR-HSP) and is the other major form of the condition.

Of the AD-HSP cases, about 40% are caused by a mutation of the SPAST (SPG4) gene, which is known to code for the production of the protein ‘spastin’.  SPG3A (10% of AD cases) codes for the protein ‘atlastin’.  Other AD genes have been localised on chromosomes including SPG8, SPG10, SPG6, and SPG12.  Scientists believe more causal genes will continue to be identified.

A comprehensive listing is available of all HSP-related genes plus detailed descriptions of location, mutations, symptoms, onset characteristics and gene comparisons.

Read more about HSP and heredity.

Is there a cure for HSP?

At present there is no cure for HSP, nor any way to reverse the disease nor halt its progress.  However, HSPers report benefits from treatments as diverse as ankle / foot surgery where tendons are relocated, to fitness and specialised treatment from neurophysiotherapists for muscle strength and range of motion.  Read more at LIVING WITH HSP on the HOME page.


State-of-the-art gene testing is available broadly across Australia. Research to find an effective treatment for HSP has been and remains the major focus of the Foundation.  The HSPRF has funded stem cell research, however there is a huge unmet need for research funding in these areas. The HSP Research Program initiated in 2007 has proved highly successful. Candidate drugs that are effective with human HSP stem cells in the laboratory have been identified. Planning for clinical trials began in late 2016.

There is also a lack of information available on management and treatment of symptoms to maintain mobility and quality of life for HSPers, another area badly needing research funding. It is hoped that clinical management guidelines will be published and available in 2018 or 2019.

Preclinical investigations to determine the action of a candidate drug in mice were initiated in early 2018. A separate drug dose modelling study was completed in late 2017. The combined results should provide a good indication of the dosing level and dosing regime needed to have the right concentration of the active drug ingredient in the neurons.

A huge challenge for HSP clinical trials is the lack of a reliable, valid and widely-accepted measure of HSP status. The need to establish such a biomarker for use in clinical trials is of the highest priority. Studies are underway in brain imaging, cerebrospinal fluid, movement analysis, urine and two blood projects in an attempt to find an HSP biomarker.

The clinical drug trial may be initiated anyway in the absence of an established biomarker, with the prospect of marked improvement in mobility and associated functioning as a very real potential outcome.

Understanding HSP in more depth

  • Craig Blackstone, MD, PhD, a senior investigator in the Neurogenetics Branch of the National Institutes of Health (NIH) and a member of the American Academy of Neurology (AAN), speaks with Neurology Now writer Stephanie Stephens about causes, symptoms, and treatments for HSP.
  • Dr. John Fink of the University of Michigan, a recognised authority on HSP, has published widely on the condition. He has authored a comprehensive overview of HSP that is updated from time to time.
  • On the SPF (USA) website is an HSP booklet in PDF format that you can download. It covers the basics of HSP and contains a lot of useful information in plain English, non-medical language… definitely worth a read!
  • Another good resource on the SPF (USA) website is a dictionary of useful words related to HSP called Words to Know!, also in PDF format that you can download. It includes a multitude of both common and technical/medical terms and provides a ready reference to help understand more about the condition.
  • Wikipedia, the online encyclopaedia, also provides a good overview of HSP.
  • Browse around this website and check out the RESOURCES section.
  • Our German colleagues have an excellent resource on their website.
  • A thorough overview of HSP has been produced in South Korean and is highly recommended. Their web-published article is an excellent ‘one-stop shop’ for learning about HSP. It is divided into the following sections:
    • Overview
    • Differential Diagnoses & Workup
    • Treatment & Medication
    • Follow-up
    • Multimedia