Spastic paraplegia 4

Title

Other Names:

SPG4; Autosomal dominant spastic paraplegia 4; Familial spastic paraplegia autosomal dominant 2; SPG4; Autosomal dominant spastic paraplegia 4; Familial spastic paraplegia autosomal dominant 2; FSP2 See More

Categories:

Congenital and Genetic Diseases; Nervous System Diseases

Summary Summary

Spastic paraplegia 4 (SPG4) is the most common type of hereditary spastic paraplegia (HSP) inherited in an autosomal dominant manner. Disease onset ranges from infancy to older adulthood. SPG4 is characterized by slowly progressive muscle weakness and spasticity (stiff or rigid muscles) in the lower half of the body. In rare cases, individuals may have a more complex form with seizures, ataxia, and dementia. SPG4 is caused by mutations in the SPAST gene.^[1]^[2] Severity of symptoms usually worsens over time, however some individuals remain mildly affected throughout their lives.^[3] Medications, such as antispastic drugs and physical therapy may aid in stretching spastic muscles and preventing contractures (fixed tightening of muscles).^[1]^[2]

Last updated: 5/27/2016

Symptoms Symptoms

Signs and symptoms of SPG4 usually become apparent in young adulthood; although symptoms may start as early as one year of age and as late as 76 years. Characteristic symptoms include stiff and rigid muscles (spasticity) and weakness in both of the legs and the lower portion of the body. Additional symptoms are different for every affected individual. Other symptoms may include:^[2]^[1]

Decreased ability to sense vibrations in the ankles
Exaggerated reflexes (hyperreflexia)
Ankle spasms
High arches in the feet (pes cavus)
Reduced bladder control
Ataxia (lack of muscle control)
Seizures

Some individuals may also experience a mild decline in cognitive function. This decline does not typically affect daily functioning.^[3]

Last updated: 5/27/2016

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Aggressive behavior	-
Agitation	-
Apathy	-
Autosomal dominant inheritance	-
Babinski sign	-
Degeneration of the lateral corticospinal tracts	-
Dementia	-
Depression	-
Disinhibition	-
Genetic anticipation	-
Hyperreflexia	-
Impaired vibration sensation in the lower limbs	-
Insidious onset	-
Intellectual disability	-
Low back pain	-
Lower limb muscle weakness	-
Memory impairment	-
Nystagmus	-
Paraplegia	-
Progressive	-
Spastic gait	-
Spastic paraplegia	-
Urinary bladder sphincter dysfunction	-
Urinary incontinence	-
Urinary urgency	-
Variable expressivity	-

Last updated: 9/1/2016

Inheritance Inheritance

SPG4 is inherited in an autosomal dominant manner.^[2] This means that having a change (mutation) in only one copy of the responsible gene in each cell is enough to cause features of the condition.

In some cases, an affected person inherits the mutated gene from an affected parent. In other cases, the mutation occurs for the first time in a person with no family history of the condition. This is called a de novo mutation.

When a person with a mutation that causes an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit that mutation.

Last updated: 5/27/2016

Treatment Treatment

Care for SPG4 is usually managed by a team including a primary care physician, neurologist, genetics professional (geneticist and/or genetic counselor), physical therapist, social worker, and psychologist. Treatment is focused on alleviating symptoms and may include:^[3]

Medications for leg spasticity (antispastic drugs)
Medications to assist in bladder control (anticholinergic antispasmodic drugs)
Regular physician therapy
Botulinum toxin and intrathecal baclofen for severe spasticity

Last updated: 5/27/2016

Management Guidelines

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.

Prognosis Prognosis

The severity of symptoms in SPG4 generally worsen over time; however, some individuals may have mild symptoms throughout their lives. Approximately 17% of individuals eventually use a wheelchair, while approximately 20% use assistance (such as a walker) to walk.^[3]

Last updated: 5/27/2016

Do you have updated information on this condition? Let us know.

Organizations Organizations

Nonprofit support and advocacy groups bring together patients, families, medical professionals, and researchers. These groups often raise awareness, provide support, and develop patient-centered information. Many are the driving force behind research for better treatments and possible cures. They can direct people to research, resources, and services. Many groups also have experts who serve as medical advisors. Visit their website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

National Ataxia Foundation
2600 Fernbrook Lane
Suite 119
Minneapolis, MN 55447-4752
Telephone: 763-553-0020
Fax: 763-553-0167
E-mail: naf@ataxia.org
Website: http://www.ataxia.org
Spastic Paraplegia Foundation
1605 Goularte Place
Fremont, CA 94539-7241
Telephone: 877-773-4483
Fax: 877-773-4483
E-mail: information@sp-foundation.org , davis77@gmail.com
Website: http://www.sp-foundation.org
Synapse: A HSP/PLS Newsletter
E-mail: synapsePLS@comcast.net

Social Networking Websites

RareConnect is an online social network for patients and families to connect with one another and share their experience living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders). Click on the link above to view the community for Hereditary spastic paraplegia.

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Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Spastic paraplegia 4. This website is maintained by the National Library of Medicine.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
The Spastic Paraplegia Foundation, a nonprofit organization supporting spastic paraplegia, offers information on Spastic paraplegia 4

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Spastic paraplegia 4. Click on the link to view a sample search on this topic.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

Have a question? Contact a GARD Information Specialist.

References References

Nance MA. Hereditary Spastic Paraplegia. National Organization for Rare Disorders (NORD). 2013; http://rarediseases.org/rare-diseases/hereditary-spastic-paraplegia/.
Spastic paraplegia 4. Genetics Home Reference. January 2008; https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-4. Accessed 5/27/2016.
Dürr A, Tallaksen C, Depienne C. Spastic Paraplegia 4. GeneReveiws. Aug 16 2012; https://www.ncbi.nlm.nih.gov/books/NBK1160.

Do you know of a review article? Send us your suggestions.