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Spinal muscular atrophy
ICD-10 G12
ICD-9 335.0-335.1
OMIM 253300 253550 253400 271150
DiseasesDB 14093 32911 12315
MedlinePlus [3]
eMedicine /
MeSH {{{MeshNumber}}}

Spinal Muscular Atrophy (SMA) is a term applied to a number of different disorders, all having in common a genetic cause and the manifestation of weakness due to loss of the motor neurons of the spinal cord and brainstem.


Infantile SMA is the most severe form. Some of the symptoms include:

  • muscle weakness
  • poor muscle tone
  • weak cry
  • limpness or a tendency to flop
  • difficulty sucking or swallowing
  • accumulation of secretions in the lungs or throat
  • the legs tend to be weaker than the arms
  • feeding difficulties
  • increased susceptibility to respiratory tract infections
  • developmental milestones, such as lifting the head or sitting up, can't be reached.

In general, the earlier the symptoms appear, the shorter the life span. The onset is sudden and dramatic. Once symptoms appear the motor neuron cells quickly deteriorate shortly after. The disease can be fatal and there is no cure for SMA yet known. The major management issue in Type 1 SMA is the prevention and early treatment of respiratory infections; pneumonia is the cause of death in the majority of the cases. Infants with Type 1 SMA have a life expectancy of less than two years, however, some grow to be adults. Intellectual and later, sexual functions, are unaffected by SMA.


In order to be diagnosed with Spinal muscular atrophy, symptoms need to be present. In most cases a diagnosis can be made by the SMN gene test, which determines whether there is at least one copy of the SMN1 gene by looking for its unique sequences (that distinguish it from the almost identical SMN2) in exons 7 and 8. In some cases, when the SMN gene test is not possible or does not show any abnormality, other tests such as an EMG electromyography (EMG) or muscle biopsy may be indicated.


The region of chromosome 5 that contains the SMN (survival motor neuron) gene has a large duplication. A large sequence that contains several genes occurs twice in adjacent segments. There are thus two copies of the gene, SMN1 and SMN2. The SMN2 gene has an additional mutation that makes it less efficient at making protein, though it does so in a low level. SMA is caused by loss of the SMN1 gene from both chromosomes. The severity of SMA, ranging from SMA 1 to SMA 3, is partly related to how well the remaining SMN 2 genes can make up for the loss of SMN 1. Often there are additional copies of SMN2, and an increasing number of SMN2 copies causes less severe disease.

All forms of SMN-associated SMA have a combined incidence of about 1 in 6,000. SMA is the most common cause of genetically determined neonatal death. The gene frequency is thus around 1:80, and approximately one in 40 persons are carriers. There are no known health consequences of being a carrier, and the only way one might know to consider the possibility is if a relative is affected.


Caused by mutation of the SMN gene[]

The most common form of SMA is caused by mutation of the SMN gene, and manifests over a wide range of severity affecting infants through adults. This spectrum has been divided arbitrarily into four groups by the level of weakness.

  • Infantile SMA - Type 1 or Werdnig-Hoffmann disease (generally 0-6 months). SMA type 1, also known as severe infantile SMA or Werdnig Hoffmann disease, is the most severe, and manifests in the first year of life with the inability to ever maintain an independent sitting position.
  • Intermediate SMA - Type 2 (generally 7-18 months). Type 2 SMA, or intermediate SMA, describes those children who are never able to stand and walk, but who are able to maintain a sitting position at least some time in their life. The onset of weakness is usually recognized some time between 6 and 18 months.
  • Juvenile SMA - Type 3 or Kugelberg-Welander disease (generally >18 months). SMA type 3 describes those who are able to walk at some time.
  • Adult SMA - Type 4. Weakness usually begins in late adolesceence in tongue, hands, or feet then progresses to other areas of the body. Course of disease is much slower and has little or no impact on life expectancy.

Statistic of forms SMA[]

Statistic of forms (from Patient Registry Report, compiled by Connie Garland for the SMA Registry, The International Coordinating Committee for clinical trials in SMA ):

  • Families: 1,386
  • Affected Individuals: 1,535
  • Affected Females – 759
  • Affected Males – 776
  • Deceased – 242
  • Living – 1,293
  • Type of SMA
  • Type 1 – 489
  • Type 2 – 511
  • Type 3 – 315
  • Adult Onset – 37
  • Kennedy Disease – 7
  • Unknown – 176

Other forms of SMA[]

Other forms of spinal muscular atrophy are caused by mutation of other genes, some known and others not yet defined. All forms of SMA have in common weakness caused by denervation, that is, the muscle atrophies because it has lost the signal to contract due to loss of the innervating nerve. Spinal muscular atrophy only affects motor nerves. Heritable disorders that cause both weakness due to motor denervation along with sensory impairment due to sensory denervation are known by the inclusive label Charcot-Marie-Tooth or Hereditary Motor Sensory Neuropathy. The term spinal muscular atrophy thus refers to atrophy of muscles due to loss of motor neurons within the spinal cord.

  • Hereditary Bulbo-Spinal SMA Kennedy's disease (X linked, Androgen receptor)
  • Spinal Muscular Atrophy with Respiratory Distress (SMARD 1) (chromsome 11, IGHMBP2 gene)
  • Distal SMA with upper limb predominance (chromosome 7, glycyl tRNA synthase)


The course of SMA is directly related to the severity of weakness. Infants with the severe form of SMA frequently succumb to respiratory disease due to weakness of the muscles that support breathing. Children with milder forms of SMA naturally live much longer although they may need extensive medical support, especially those at the more severe end of the spectrum.

Although gene replacement strategies are being tested in animals, current treatment for SMA consists of prevention and management of the secondary effect of chronic motor unit loss. It is likely that gene replacement for SMA will require many more years of investigation before it can be applied to humans. Due to molecular biology, there is a better understanding of SMA. The disease is caused by deficiency of SMN (survival motor neuron) protein, and therefore approaches to developing treatment include searching for drugs that increase SMN levels, enhance residual SMN function, or compensate for its loss.

Much can be done for SMA patients in terms of medical and in particular respiratory, nutritional and rehabilitation care. However, there is currently no drug known to alter the course of SMA. Significant progress has been made in preclincial research towards an effective treatment. Several drugs have been identified in laboratory experiments that hold promise for patients. To evaluate if these drugs benefit SMA patients, clinical trials are needed. In a clinical trial a new medication is tested while the patients are carefully monitored for their safety and for any possible drug effects, positive or negative.

Some drugs under clinical investigation for the treatment of SMA:


In 1978 Pearn published a series of papers on SMA. He reported that childhood onset SMA is not an uncommon disease and has an incidence in the Northern UK in range of 4 per 100,000 births. At that time the association between the severe infantile form of SMA and the milder forms was not understood. With the advantage of knowledge about the causative gene, it is now known that SMA1, SMA2 and SMA3 are all caused by mutations in the same gene. The overall incidence of SMA, of all types, is in the range of 1 peer 6,000 individual. It affects individuals of all races, unlike other well known autosomal recessive disorders like sickle cell disease, and cystic fibrosis, that have significant differences in occurrence rate between races. Overall, SMA1 is the most common genetic cause of death in infants.

As an autosomal recessive disorder, all forms of SMA are caused by inheritance of a mutated gene from each parent, who would not know that they have the abnormal gene because having only one mutated copy produces no symptoms. Once a child is affected, each subsequent baby has a 25% chance of having the illness. If a sibling does not inherit the disorder, he or she has a 2/3 chance of being a carrier. Couples may want to have genetic counseling before deciding to have more children. Counseling is available to these families through the community.

In 1990 mapping of the gene for SMA to chromosome 5q11.2-13.3 was reported and culminated in a 3 year research funded in part by the Muscular Dystrophy Association. The findings were also confirmed by French researchers. The identification of the gene for autosomal recessive SMA on chromosome 5q has allowed for prenatal diagnosis. Families who are at risk, or who have had a child with the diagnosis can have an amniocentesis done during pregnancy for DNA testing.

Adults with SMA[]

Although SMA often results in death during childhood, some people with SMA survive into adulthood and even old age. Actual lifespan depends greatly on the severity of SMA in each individual, and the three major types of SMA provide only a rough diagnostic guide; however even some individuals diagnosed with type-1 SMA survive to adulthood. Intellectual ability is unaffected by SMA, and adults with SMA benefit greatly from the use of assistive technology, such as speech recognition or Switch Access software. Such devices allow people with even very limited mobility to use a computer to read, write, communicate, play video games, and access environmental controls. Sexual response and reproductive functions are also unaffected by SMA; individuals with SMA can enjoy active sex lives and have given birth to children.

One example of an adult living with SMA-I is Ami Ankilewitz, who was 34 years old as of 2005, outliving his predicted life expectancy by 28 years. His experiences are presented in the documentary 39 Pounds of Love, whose title refers to his total body weight.

Another example is Mark Siegel, a 33-year-old (as of 2007) attorney with Type II SMA living in Minneapolis, Minnesota. He maintains a daily blog called The 19th Floor.

The 'Baby MB' Case[]

On March 15th 2006, the High Court of Justice of England and Wales ruled that 17 month old "Baby MB" (identity withheld) was to be kept alive, contrary to 14 medical professional's advice - one of the medics 'Dr. S' stating "I think that the cumulative effect of the condition's effects is that he has an intolerable life" [1]. The judge said that "he felt the child gained enough pleasure from life to outweigh the medical evidence of his condition" [2].

Specialists' reactions: [4]


See also[]

  • Polyneuropathy in dogs and cats

External links[]

  • Fight SMA - An international nonprofit dedicated to finding a treatment or cure for spinal muscular atrophy
  • [5] - Families of Spinal Muscular Atrophy. An international nonprofit dedicated to providing support for individuals with sma and families of the individual with sma.
  1. REDIRECT Template:CNS diseases of the nervous system
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