Rare Dermatology News

Disease Profile

Stiff person syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

Adult

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ICD-10

G25.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Stiff man syndrome; Morsch Woltman syndrome; SPS;

Categories

Congenital and Genetic Diseases; Endocrine Diseases; Musculoskeletal Diseases;

Summary

Stiff person syndrome (SPS) is a rare, progressive syndrome that affects the nervous system, specifically the brain and spinal cord. Symptoms may include extreme muscle stiffness, rigidity and painful spasms in the trunk and limbs, severely impairing mobility. Spasms can generate enough force to fracture bone. People with SPS often have heightened sensitivity to noise, sudden movements, and emotional distress, which can set off muscle spasms. Persistent symptoms can lead to abnormal posturing of the spine, such as being hunched over. The syndrome affects twice as many women as men.[1][2]

SPS is caused by increased muscle activity due to decreased inhibition of the central nervous system. It is thought to have an autoimmune component and is often associated with diabetes, as well as other autoimmune diseases such as thyroiditis, vitiligo, and pernicious anemia.[1][2] It may be diagnosed after having various tests including blood tests (such as for glutamic acid decarboxylase (GAD) antibodies which is elevated in about 2 in 3 people with SPS), a lumbar puncture, and electromyography. Treatment aims to control symptoms and improve mobility. Examples of treatments that have been used for SPS, include benzodiazepines, muscle relaxants, intravenous immune globulin (IVIG) therapyplasmapheresis (also called plasma exchange), and rituximab.[1][2] While some people with SPS may maintain reasonable levels of activity with treatment, the majority become disabled over time.[2]

Symptoms

Stiff person syndrome (SPS) is a progressive syndrome characterized by recurrent episodes of severe muscle stiffness, rigidity, and painful spasms in the trunk and limbs. The age that symptoms begin can vary, but most people start experiencing symptoms between ages 30 and 60. Spasms can be prolonged and extremely forceful, with the ability to generate enough force to fracture bone. They may cause a person to fall when walking or standing. Spasms are especially likely or may worsen during times of emotional distress, when being touched, when there is sudden movement, or with noise.[2][3]

Over time, persistent symptoms can lead to abnormal posturing of the spine, such as being stiffened and hunched over.[1] Daily activities such as getting into or out of bed, getting up from a chair, or dressing may become increasingly difficult.[2] People with SPS also may become fearful and anxious about navigating daily life, which in turn may trigger additional spasms. Many people with SPS develop depression as the syndrome progresses and quality of life becomes severely impaired.[2][3]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Anxiety
Excessive, persistent worry and fear
0000739
EMG abnormality
0003457
Falls
0002527
Hyperhidrosis
Excessive sweating
Increased sweating
Profuse sweating
Sweating
Sweating profusely
Sweating, increased

[ more ]

0000975
Intermittent painful muscle spasms
0011964
30%-79% of people have these symptoms
Agoraphobia
Fear of open spaces
0000756
Autoimmune antibody positivity
0030057
Difficulty walking
Difficulty in walking
0002355
Emotional lability
Emotional instability
0000712
Exaggerated startle response
0002267
Paraspinal muscle hypertrophy
0012894
Rigidity
Muscle rigidity
0002063
5%-29% of people have these symptoms
Diabetes mellitus
0000819
Hypothyroidism
Underactive thyroid
0000821
Lumbar hyperlordosis
Excessive inward curvature of lower spine
0002938
Percent of people who have these symptoms is not available through HPO
Adult onset
Symptoms begin in adulthood
0003581
Anemia
Low number of red blood cells or hemoglobin
0001903
Asymmetric limb muscle stiffness
0007156
Autoimmunity
Autoimmune disease
Autoimmune disorder

[ more ]

0002960
Axial muscle stiffness
0006921
Depressivity
Depression
0000716
Fever
0001945
Frequent falls
0002359
Hyperreflexia
Increased reflexes
0001347
Hypertension
0000822
Myoclonic spasms
0003739
Opisthotonus
0002179
Proximal limb muscle stiffness
0007066
Sporadic
No previous family history
0003745
Tachycardia
Fast heart rate
Heart racing
Racing heart

[ more ]

0001649
Vitiligo
Blotchy loss of skin color
0001045

Cause

Scientists don’t yet understand the complete picture of what causes stiff person syndrome, but research indicates that it is the result of an abnormal autoimmune response in the brain and spinal cord.[1] Autoimmune responses occur when the immune system mistakenly attacks the body.

Most people with stiff person syndrome have antibodies that are made to attack glutamic acid decarboxylase (GAD). GAD is a protein in some neurons that are involved in making a substance called gamma-aminobutyric acid (GABA), which is responsible for controlling muscle movement. The symptoms of stiff person syndrome may develop when the immune system mistakenly attacks the neurons that produce GAD. When GAD is not working properly, there is not enough GABA to help control muscle movement. The exact role that deficiency of GAD plays in the development of stiff person syndrome is not fully understood.[3]

Some individuals with stiff person syndrome will have antibodies to amphiphysin, a protein involved in the transmission of signals from one neuron to another. Individuals with these antibodies have a higher risk for developing breast, lung, or colon cancer.[3][4][5][6]

Diagnosis

A diagnosis of stiff person syndrome (SPS) is typically made based on symptoms, a detailed medical history, and various tests used to support the diagnosis or rule out other diseases with overlapping symptoms.[4][8] One commonly used test is a blood test to detect the presence of glutamic acid decarboxylase (GAD) antibodies. About 60-80% of people with SPS have antibodies against GAD that can be detected on a blood test.[8] The absence of GAD antibodies does not rule out SPS, but the presence of high levels of GAD antibodies strongly supports the diagnosis.[5] GAD antibodies may also be measured in the cerebral spinal fluid from a lumbar puncture.[9]

Additionally, a doctor may recommend electromyography (EMG), which records electrical activity in skeletal muscles.[4][8] The EMG of a person with SPS typically shows continuous motor activity in the skeletal muscles.[4][8]

Other testing that may be used to confirm or rule out the diagnosis includes:

Genetic testing currently is not available because the underlying genetic cause of stiff person syndrome has not been established.[5]

Treatment

Treatment aims to control symptoms and improve mobility and function. While some people on treatment for SPS may maintain reasonable levels of activity, the majority become increasingly disabled over time. Treatment options depend on the symptoms and severity in each person and may include:[2][3]

  • Benzodiazepines these are drugs that slow down the nervous system and may relieve muscle spasms and anxiety. They are generally considered the best initial therapy for SPS. Examples include diazepam and clonazepam.
  • Baclofen this is a muscle relaxant that may be used for people in whom benzodiazepines are not effective or not well-tolerated. Some people benefit from using baclofen in addition to benzodiazepines.
  • Immune modulating therapies these may be considered in people with severe symptoms who do not experience relief with benzodiazepines and baclofen. Options may include intravenous immune globulin (IVIG) therapy, plasmapheresis (also called plasma exchange), and rituximab. However studies supporting the effectiveness and safety of these therapies for SPS are limited.

Physical therapy and occupational therapy are also an important part of management for SPS and may help with side effects of medications (such as weakness) in addition to symptoms of the disease.[3]

Management Guidelines

  • Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s 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

      Organizations Providing General Support

        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

          In-Depth Information

          • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
          • 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 Stiff person syndrome. Click on the link to view a sample search on this topic.

            References

            1. NINDS Stiff-Person Syndrome Information Page. National Institute of Neurological Disorders and Stroke. https://www.ninds.nih.gov/Disorders/All-Disorders/Stiff-Person-Syndrome-Information-Page#disorders-r1. Accessed 7/12/2017.
            2. Helfgott SM. Stiff-person syndrome. UpToDate. Waltham, MA: UpToDate; December 28, 2016; https://www.uptodate.com/contents/stiff-person-syndrome.
            3. Rodgers-Neame NT. Stiff Person Syndrome. Medscape Reference. May 30, 2017; https://emedicine.medscape.com/article/1172135-overview.
            4. Murinson BB. Stiff Person Syndrome. National Organization for Rare Disorders (NORD). 2010; https://rarediseases.org/rare-diseases/stiff-person-syndrome/.
            5. Stiff Person Syndrome. Johns Hopkins Medicine: Neurology & Neurosurgery. https://www.hopkinsmedicine.org/neurology_neurosurgery/centers_clinics/neuroimmunology_and_neurological_infections/conditions/stiff_person_syndrome.html.
            6. Meinck HM. Stiff person syndrome and related disorders. Orphanet. August 2007; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=3198.
            7. Stiff-Person Syndrome; SPS. Online Mendelian Inheritance in Man (OMIM). August 31, 2016; https://www.ncbi.nlm.nih.gov/omim/184850.
            8. Sanders S, Bredeson C, Pringle CE, et. al. Autologous stem cell transplantation for stiff person syndrome: two cases from the Ottawa blood and marrow transplant program. JAMA Neurology. October, 2014; 71(10):1296-9. https://jamanetwork.com/journals/jamaneurology/fullarticle/1897093.
            9. Rakocevic G, Raju R, Dalakas MC. Anti-glutamic acid decarboxylase antibodies in the serum and cerebrospinal fluid of patients with stiff-person syndrome: correlation with clinical severity. Arch Neurol. June, 2004; 61(6):902-904. https://www.ncbi.nlm.nih.gov/pubmed/15210528.

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