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Disease Profile

Proximal spinal muscular atrophy

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 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

All ages

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ICD-10

G12.0 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)

SMA

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
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Orpha Number: 70

Definition
Proximal spinal muscular atrophies are a group of neuromuscular disorders characterized by progressive muscle weakness 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 1/30,000.

Clinical description
Four subtypes have been defined according to the age of onset and severity of the disease: type 1 (SMA1), the most severe form, with onset before six months of age; type 2 (SMA2), with onset between 6 and 18 months of age, type 3 (SMA3), with onset between childhood and adolescence, and type 4 (SMA4), the least severe form, with adult onset (see these terms). All types are characterized by muscle weakness and atrophy of varying severity, particularly affecting the lower limbs and respiratory muscles. The weakness is almost always symmetric and progressive. Scoliosis, muscle retractions, and joint contractures may occur. Constipation and gastroesophageal reflux are frequent.

Etiology
Around 95% of cases of SMA are caused by homozygous deletions (either of exon 7, or of exons 7 and 8) in the SMN1 gene (5q12.2-q13.3) encoding the SMN (survival motor neuron) protein. A second SMN gene (SMN2; 5q13.2) has also been identified and contributes to the production of only 10% of the full-length SMN protein. However, although there is some variation, disease severity in SMA is inversely correlated with the number of copies of the SMN2 gene, with patients with three or four copies more frequently manifesting SMA3/4, rather than SMA1. Deletions of the NAIP (5q13.1) gene have also been identified and may play a role in modifying disease severity.

Diagnostic methods
Diagnosis is based on clinical history and examination and can be confirmed by genetic testing. Electromyography and muscle biopsy may also be performed.

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 feasible through molecular analysis of amniocytes or chorionic villus samples.

Genetic counseling
Transmission of SMN1 and NAIP deletions is autosomal recessive. 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 are ongoing to identify potential drug treatments for SMA, mainly targeted towards increasing the levels of the full length SMN protein. However, at present, management remains symptomatic, involving a multidisciplinary approach that aims to improve quality of life. Physiotherapy and occupational and respiratory therapies are necessary. Noninvasive ventilation and gastrostomy may be required. Antibiotic therapy is used in case of pulmonary infection. The scoliosis and joint manifestations may require surgical correction. Patients may require a wheelchair, or use a corset/back brace for support.

Prognosis
The prognosis depends on the severity of the disease, which generally correlates with the age of onset: earlier-onset forms are generally associated with a poor prognosis, whereas life expectancy may be close to normal in later-onset forms. Death may occur due to respiratory insufficiency and infections.

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
80%-99% of people have these symptoms
EMG abnormality
0003457
Hemiplegia/hemiparesis
Paralysis or weakness of one side of body
0004374
Muscular hypotonia
Low or weak muscle tone
0001252
Proximal lower limb amyotrophy
Wasting of thigh muscle
0008956
Reduced tendon reflexes
0001315
30%-79% of people have these symptoms
Abnormality of the ribs
Rib abnormalities
0000772
Abnormality of the voice
Voice abnormality
0001608
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation

[ more ]

0001511
Joint stiffness
Stiff joint
Stiff joints

[ more ]

0001387
Lymphedema
Swelling caused by excess lymph fluid under skin
0001004
Polyhydramnios
High levels of amniotic fluid
0001561
Preauricular skin tag
0000384
Recurrent fractures
Increased fracture rate
Increased fractures
Multiple fractures
Multiple spontaneous fractures
Varying degree of multiple fractures

[ more ]

0002757

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.

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.
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.