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Disease Profile

Spinal muscular atrophy type 4

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.

Unknown

Age of onset

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ICD-10

#N/A

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)

Spinal muscular atrophy, adult form; SMA 4; Spinal muscular atrophy 4;

Categories

Musculoskeletal Diseases

Summary

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

Orpha Number: 83420

Definition
Proximal spinal muscular atrophy type 4 (SMA4) is the adult-onset 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 1/300,000.

Clinical description
SMA4 usually manifests in the second or third decade of life. The muscle weakness predominantly affects the legs and hip muscles and then progresses to the shoulders and arms. Waddling gait is common. Finger trembling, fasciculation and calf hypertrophy may occur. The clinical picture is similar to that seen in SMA3 (see this term) but the motor weakness is less severe in SMA4.

Etiology
As for the other forms of SMA, SMA4 has been associated with 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) and some studies have shown that patients with the mild SMA4 form have multiple (four to six) SMN2 copies. However, no SMN1 gene mutations are found in some patients diagnosed with SMA4 and in these cases the genetic anomalies remain to be identified.

Diagnostic methods
The diagnosis is based on clinical history and examination. In patients with SMN1 anomalies, the diagnosis may be confirmed by genetic testing. Electromyography and muscle biopsy may be necessary.

Differential diagnosis
Differential diagnoses include the amyotrophic lateral sclerosis, primary lateral sclerosis, myasthenia gravis, and carbohydrate metabolism disorders (see these terms).

Antenatal diagnosis
Prenatal diagnosis is possible for families in which the mutations in the SMN1 gene have been identified.

Genetic counseling
The SMN1 gene deletions are transmitted in an autosomal recessive manner. Genetic counseling should be provided.

Management and treatment
Management is symptomatic, involves a multidisciplinary approach, and aims to improve quality of life. Physiotherapy and occupational therapies are recommended. 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 SMA4 patients.

Prognosis
SMA4 is the mildest form of SMA and in general the disease course is benign with patients having a normal life expectancy.

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
Adult onset
Symptoms begin in adulthood
0003581
Areflexia of lower limbs
0002522
Autosomal recessive inheritance
0000007
Degeneration of anterior horn cells
0002398
EMG: neuropathic changes
0003445
Hand tremor
Tremor of hand
Tremor of hands
tremors in hands

[ more ]

0002378
Proximal amyotrophy
Wasting of muscles near the body
0007126
Proximal muscle weakness
Weakness in muscles of upper arms and upper legs
0003701
Slow progression
Signs and symptoms worsen slowly with time
0003677
Spinal muscular atrophy
Spinal muscle degeneration
Spinal muscle wasting

[ more ]

0007269
Tongue fasciculations
Tongue twitching
Twitching of the tongue

[ more ]

0001308

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    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).
        • Genetics Home Reference (GHR) contains information on Spinal muscular atrophy type 4. This website is maintained by the National Library of Medicine.

          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 Spinal muscular atrophy type 4. Click on the link to view a sample search on this topic.