Spinal muscular atrophy type 3

Información en español Title

Other Names:

SMA3; Muscular atrophy, juvenile; SMA 3; SMA3; Muscular atrophy, juvenile; SMA 3; Kugelberg-Welander syndrome; KWS; Spinal muscular atrophy, mild childhood and adolescent form See More

Categories:

Congenital and Genetic Diseases; Musculoskeletal Diseases; Nervous System Diseases

This disease is grouped under:

Spinal muscular atrophy

Summary Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.

Orpha Number: 83419

Definition

Proximal spinal muscular atrophy type 3 (SMA3) is a relatively mild form of proximal spinal muscular atrophy (see this term) characterized by muscle weakness and hypotonia resulting from the degeneration and loss of the lower motor neurons in the spinal cord and the brain stem nuclei.

Epidemiology

Prevalence is estimated at around 1/375,000.

Clinical description

The disease manifests after 12 months of age (usually between childhood and adolescence), after ambulation has been acquired. Two subtypes (SMA3a and SMA3b) have been distinguished by some authors: SMA3a defines patients with onset before the age of 3 years, whereas SMA3b defines patients with onset after 3 years. Difficulties walking, running, and going up and down stairs are common. The muscle weakness predominantly affects the legs and hip muscles and then progresses to the shoulders and arms. Legs are always more severely affected than arms. Weak finger trembling and scoliosis are frequent and the patellar reflex is absent.

Etiology

As for other forms of SMA, SMA3 is primarily caused by deletions in the SMN1 gene (5q12.2-q13.3) encoding the SMN (survival motor neuron) protein. Although there is some variation, disease severity in SMA is inversely correlated with the number of copies of the second SMN gene (SMN2; 5q13.2), with patients with MSA3 having three (SMA3a) or four (SMA3b) SMN2copies. Deletions of the NAIP (5q13.1) gene, which may play a role in modifying disease severity, have also been identified in SMA3 patients but are less frequent than in individuals with SMA1 and 2.

Diagnostic methods

Diagnosis is based on clinical history and examination but is confirmed by genetic testing. Electromyography and muscle biopsy may be necessary.

Differential diagnosis

Differential diagnoses include amyotrophic lateral sclerosis, congenital muscular dystrophies, congenital myopathies, primary lateral sclerosis, myasthenia gravis, and carbohydrate metabolism disorders (see these terms).

Antenatal diagnosis

Antenatal diagnosis is possible through molecular analysis of amniocytes or chorionic villus samples.

Genetic counseling

Transmission is autosomal recessive but around 2% of cases are caused by de novo mutations. Genetic counseling should be offered to patients and their families.

Management and treatment

Clinical trials to identify specific drug treatments for SMA are ongoing, and preliminary studies have indicated that valproic acid (as a histone deacetylase inhibitor) may improve quantitative muscle strength and subjective motor function in SMA3 patients. However, at present, management is symptomatic, involving a multidisciplinary approach aiming to improve quality of life. Physiotherapy and occupational therapies are recommended.

Prognosis

A wheelchair may be required during childhood for some patients (more commonly those with SMA3a), whilst others retain the ability to walk into adulthood (more commonly those with SMA3b). SMA3 progresses slowly and life expectancy is usually normal. However, deformities of the vertebral column are frequent and complications may lead to respiratory restriction.

Visit the Orphanet disease page for more resources.

Last updated: 7/1/2009

Symptoms Symptoms

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.

Showing of 12 |

Medical Terms	Other Names	Learn More: HPO ID
Percent of people who have these symptoms is not available through HPO
Areflexia of lower limbs		0002522
Autosomal recessive inheritance		0000007
Degeneration of anterior horn cells		0002398
EMG abnormality		0003457
Hand tremor	Tremor of hand Tremor of hands tremors in hands [ more ]	0002378
Hyporeflexia	Decreased reflex response Decreased reflexes [ more ]	0001265
Limb fasciculations		0007289
Muscle spasm		0003394
Progressive	Worsens with time	0003676
Proximal muscle weakness	Weakness in muscles of upper arms and upper legs	0003701
Spinal muscular atrophy	Spinal muscle degeneration Spinal muscle wasting [ more ]	0007269
Tongue fasciculations	Tongue twitching Twitching of the tongue [ more ]	0001308

Showing of 12 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 2/1/2021

Do you have updated information on this disease? We want to hear from you.

Treatment Treatment

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

Risdiplam (Brand name: Evrysdi) - Manufactured by Genentech
FDA-approved indication: August 2020, risdiplam (Evrysdi) was approved for the treatment of spinal muscular atrophy (SMA) in patients 2 months of age and older.
National Library of Medicine Drug Information Portal
Nusinersen (Brand name: Spinraza) - Manufactured by Biogen, Inc
FDA-approved indication: December 2016, nusinersen (Spinraza) was approved for the treatment of spinal muscular atrophy in pediatric and adult patients.
National Library of Medicine Drug Information Portal
Medline Plus Health Information
Onasemnogene abeparvovec (Brand name: Zolgensma) - Manufactured by AveXis, Inc.
FDA-approved indication: May 2019, onasemnogene abeparvovec (Zolgensma) was approved for the treatment of pediatric patients less than 2 years of age with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene.
National Library of Medicine Drug Information Portal

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Get answers to care and health-related questions about SMA from the advocacy organization, Families of SMA's Medical Advisory Council experts. Their free Ask the Expert feature connects you with SMA physicians and clinicians, who can answer questions on a wide variety of health-related topics. Click on the link to learn more.
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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 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 MedlinePlus Genetics.

Organizations 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

Cure SMA
925 Busse Road
Elk Grove, IL 60007
Toll-free: 800-886-1762
Telephone: 847-367-7620
Fax: 847-367-7623
E-mail: info@curesma.org
Website: http://www.curesma.org
SMA Europe
Europe,
Telephone: +44 (0)1789 801159
E-mail: vanessa@sma-europe.eu
Website: http://www.sma-europe.eu/
SMA Gruba
Turkey
Telephone: 0535 715 3781
E-mail: smagruba-iletisim@hotmail.com
Website: http://smagrubu.net/
Spinal Muscular Atrophy Association of Australia Inc. (SMA Australia)
PO Box 5245 (mail)
Unit 7 16-28 Melverton Drive (office)
Hallam Vic, 3803 Australia
Telephone: (03) 9796 5744
Fax: 03 83737 7787
E-mail: smaaa@smaaustralia.org.au
Website: http://smaaustralia.org.au/
Spinal Muscular Atrophy Foundation
888 Seventh Avenue
Suite 400
New York, NY 10019
Toll-free: 877-FUND-SMA (877-386-3762)
Telephone: 646-253-7100
Fax: 212-247-3079
E-mail: info@smafoundation.org
Website: http://www.smafoundation.org

Organizations Providing General Support

Muscular Dystrophy Association (MDA)
222 S Riverside Plaza
Suite 1500
Chicago, IL 60606
Toll-free: 1-833-275-6321 (Helpline)
E-mail: resourcecenter@mdausa.org
Website: https://www.mda.org

Do you know of an organization? We want to hear from you.

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

Families of SMA has created a booklet entitled Understanding SMA that is intended to serve as a source of information and support for children and adults with Spinal Muscular Atrophy (SMA).
MedlinePlus Genetics contains information on Spinal muscular atrophy type 3. This website is maintained by the National Library of Medicine.
The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.

In-Depth Information

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.
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 Spinal muscular atrophy type 3. Click on the link to view a sample search on this topic.

GARD Answers GARD Answers

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