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Disease Profile

Spinal muscular atrophy type 3

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

Childhood

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ICD-10

G12.1

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)

SMA3; Muscular atrophy, juvenile; SMA 3;

Categories

Congenital and Genetic Diseases; Musculoskeletal Diseases; Nervous System Diseases

Summary

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

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.

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.

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

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.

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

      • 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.