About SMA:

Frequently Asked Questions

What is Spinal Muscular Atrophy?

Spinal Muscular Atrophy (SMA) is an inherited disease characterized by muscle atrophy and loss of motor function, caused by the absence of or defect in the Survival Motor Neuron 1 (SMN1) gene. The SMN1 gene encodes for survival of motor neuron (SMN) protein. This protein is critical to the survival and health of α-motor neurons, which are nerve cells in the spinal cord responsible for muscle contraction. As the motor neurons become unhealthy due to the reduced SMN levels, muscles weaken and become atrophic. For more information about SMA, please see the SMA Overview.

What are the symptoms of SMA?

SMA is characterized by a progressive loss of muscle control and movement and increasing weakness due to the loss of motor neurons in the spinal cord. Proximal muscles (muscles closest to the center of the body, such as those in the trunk and neck) are more severely affected than distal muscles (muscles furthest from the center of the body, such as those in the hands and feet). Normal growth and development can place additional demands on already weakened muscles. There is a wide range of severity of SMA; however, even in its moderate form, SMA can limit function and mobility. People with SMA either never acquire, or progressively lose, the ability to walk, stand, sit and eventually move. Although the disease varies in terms of age of onset and severity, most patients start to show symptoms during infancy or as toddlers. People with SMA often develop bone and/or spinal deformities which may require surgical treatment. Respiratory illnesses may be more common for people living with SMA and can be severe. Good multidisciplinary care, including physical therapy, occupational therapy, respiratory therapy, and nutritional support, can improve quality and length of life for people with SMA and is recommended. It is important to note that children with SMA undergo normal intellectual and emotional development and, with help and support, can participate in many childhood activities. For more information, please see A Guide to SMA Standard of Care.

What are the different forms of SMA?

Type I, Acute Form of SMA (Werdnig-Hoffmann Disease): Patients typically exhibit limited movement and have difficulty holding their head straight, feeding, and swallowing. Reduced strength in the chest muscles often results in labored breathing with the chest appearing sunken. The progressive weakening of the muscles leads to respiratory infections, lung collapse and eventual death, usually by the age of two years. About 60% of patients with SMA are born with this form of the disease.

Type II, Intermediate Form of SMA: Symptoms usually emerge in patients between six and eighteen months, and the progression of symptoms varies greatly. Infants and children with this form of the disease are at one time able to sit unassisted, but do not walk independently. Due to the varied progression of symptoms, life expectancy ranges from early childhood to adulthood. The majority of Type II patients live into adulthood.

Type III, Mild Form of SMA (Kugelberg-Welander or Juvenile Spinal Muscular Atrophy): Symptoms typically appear between eighteen months and early adulthood. People with SMA Type III often exhibit difficulty walking, have mild muscle weakness and are at risk for respiratory infections. These patients have a normal life expectancy.

Type IV, Adult Form of SMA: A less common form of SMA that afflicts adults and is characterized by a slower progression of symptoms that particularly affect walking. Symptoms typically emerge after age 35.

What is the life expectancy for people who have SMA?

SMA is a genetic disease characterized by progressive muscle weakening and loss. Because the muscles controlling breathing are affected by the disease, SMA can cause premature death. Life expectancy of SMA tends to vary by SMA type, which is generally associated with age of onset of symptoms. Children diagnosed with SMA Type I may survive for up to two years or longer, depending on their individual strength. Children with moderate to mild forms of SMA (SMA Types II and III) generally live into adulthood and could have normal life expectancy. Good multidisciplinary care, including physical therapy, occupational therapy, respiratory therapy, and nutritional support, can improve quality and length of life for people with SMA and is recommended. Planning for medical emergencies is also strongly suggested. For more information, please see A Guide to SMA Standard of Care.

What is the current standard of care for SMA patients?

Many people living with SMA need constant, ongoing care from their families and from a variety of medical specialists. A Guide to SMA Standard of Care, prepared by the Patient Advisory Group of the International Coordinating Committee for SMA Clinical Trials, highlights the following five recommendations for care of children with SMA:

1) Confirm the diagnosis of SMA: Confirmation of SMA diagnosis with a simple genetic blood test can help medical professionals plan for and provide disease-specific patient care.

2) Manage breathing: Respiratory problems are the top cause of illness and the most common cause of death among children with SMA Type I and II. Patients and families can learn about and practice techniques to maintain a clear airway, take measures to prevent respiratory problems, and learn how to minimize the impact of respiratory infection.

3) Manage eating and nutrition: Children with SMA are susceptible to over- and under-nutrition problems. It is important that families and healthcare professionals work together to monitor the child’s growth and develop a personalized nutrition plan.

4) Manage movement and daily activities: Maintaining function of trunk, arm, leg, and neck muscles enables people with SMA to achieve their highest level of function and independence. Health care professionals can design an individualized physical therapy plan and incorporate use of assistive devices to support function and help slow or prevent complications of SMA.

5) Prepare for illness: Families are encouraged to develop a plan for medical emergencies and to share the plan with all healthcare professionals participating in caring for the child.

How can I find a doctor who specializes in SMA?

You can visit the Pediatric Neuromuscular Clinical Research Network (PNCR) website for the list of SMA clinics located on the east coast. If your area does not have an SMA clinic, the Muscular Dystrophy Association (MDA) website has a listing of MDA-sponsored clinics within the U.S. that provide specialty care and support for patients with different types of neuromuscular diseases, including SMA.

How common is SMA?

SMA has generally been believed to affect as many as 10,000 to 25,000 children and adults in the United States, and therefore it is one of the most common rare diseases. The number of people living with the SMA is comparable to better-known diseases such as ALS (Lou Gehrig’s Disease) and Cystic fibrosis. One in 6,000 to one in 10,000 children are born with the disease, making the incidence rate of SMA similar to that of Tay-Sachs Disease (in the Jewish population) and Duchenne muscular dystrophy. Although SMA affects all ethnic groups, the incidence of the disease may vary by population. Approximately 1 in 50 people (~6 million Americans) are carriers of SMA, and do not exhibit SMA symptoms but have or ‘carry’ mutations in the SMN1 gene.

How is SMA diagnosed?

A simple blood test designed to identify deletions and mutations in the Survival Motor Neuron 1 (SMN1) gene is typically used to confirm a diagnosis of SMA. For a listing of clinics and laboratories offering the genetic test for SMA, please visit the NCBI website. If symptoms are present and there is no indication of a typical SMA gene mutation, additional genetic studies, a muscle biopsy, and/or electromyography (EMG) may be necessary to confirm the diagnosis.

Where can I find information on carrier screening for SMA?

A carrier of SMA is someone who has one defective copy of the SMN1 gene and one normal SMN1 copy. Approximately 1 in 50 Americans are carriers of SMA. SMA carriers do not experience the symptoms of the disease because their single, normal SMN1 copy is enough to make all SMN protein the body needs. However, if two carriers of SMA have a child together, there is a 1 in 4 chance that the child will inherit a defective copy of SMN1 from both parents and will have SMA. Carrier screening is a type of genetic testing that couples may choose to take if they want to find out whether they have certain deletions or mutations that cause some autosomal recessive diseases, such as SMA. In about 97% of cases, carrier screening can determine if someone is a carrier of SMA. Individuals and couples considering carrier screening for SMA, may find it helpful to talk with an obstetrician/gynecologist or a genetic counselor to gather more information. Genetic counselors in your area can be located through the National Society of Genetic Counselors website.

What are the genetics of SMA?

SMA is an autosomal recessive disease, caused by a deletion or mutation in the Survival Motor Neuron 1 (SMN1) gene. Most people have two copies of the SMN1 gene, one inherited from their mother and the other from their father. However, carriers of SMA (approximately 1 in 50 Americans) have one normal copy of SMN1 and one mutated or defective copy. Having at least one normal SMN1 copy will allow a person to produce more than enough SMN protein to prevent any symptoms of SMA, so carriers do not show any symptoms of the disease.

SMA usually occurs in children of couples who are both carriers of SMA, each parent having one normal and one defective SMN1 copy. Because carriers of SMA have an equal chance of passing on a normal or defective copy of SMN1, there are three possible combinations of parental SMN1 copies that determine if the offspring will be affected by SMA. Children of two SMA carriers have a:

25% chance of inheriting two normal copies of SMN1. These children will not have SMA and will not be carriers of SMA.
50% chance of inheriting one normal and one defective copy of SMN1. These children will not have SMA but will be carriers of SMA.
25% chance of inheriting 2 defective copies of SMN1. These children will have SMA.

These three possibilities are illustrated by the Punnett square diagram (below), a tool that can be used to explain inheritance of autosomal recessive traits and disorders, like SMA. The capital S represents a normal SMN1 copy, while the lower case ‘s’ represents a mutated SMN1 copy. The Punnett square shows the combinations of the healthy and defective SMN1 copies.

Though all people with SMA have two mutated copies of SMN1, not all patients are affected at the same severity. Other genes, such as SMN2, are modifiers of the disease and can make the symptoms of SMA less severe.

What is the SMN2 gene and why is it so important?

Muscle weakness and atrophy in SMA results from the deficiency of a critical protein called SMN. The SMN1 gene is primarily responsible for making SMN protein; however, most people also have a partially functioning “backup gene” called SMN2, which produces small amounts of SMN protein. Each person with SMA has at least one copy of the SMN2 gene. Although there is not a perfect correlation between SMN2 copy number and disease severity, studies have shown that people with SMA who have more copies of SMN2 tend to have a less severe form of the disease than people who have fewer SMN2 gene copies. Because of its similarity to SMN1 and its ability to produce small amounts of SMN protein, one of the main therapeutic mechanisms for the treatment of SMA is to increase SMN2 gene expression. It is thought that if the SMN2 gene could be modified to produce enough functional SMN protein, motor neuron and muscle function losses could be slowed, prevented, or even restored in people who have SMA. For more information on the importance of the SMN2 gene in people with SMA, please see the SMA Overview.

Why is the research outlook so promising?

Dramatic breakthroughs have been made in the past fifteen years, catapulting SMA from a disease that was poorly understood to one on the threshold of treatment. The SMN1 gene responsible for the disease has been identified. Scientists have discovered the gene produces the SMN protein and have learned about its functions. Another critical scientific finding was the discovery of the partially functioning “backup gene,” the SMN2 gene, which makes small amounts of the same critical SMN protein. Several academic institutions, biotech and pharmaceutical companies are working on finding drugs to increase expression of SMN protein from the SMN2 gene. The current thinking is that the greater the amount of functional SMN protein produced by SMN2, the more motor neurons can be kept healthy, slowing or preventing the progression of SMA symptoms.

The development of mouse models of SMA that imitate the human range in disease severity have provided valuable insights into disease mechanisms, natural history, and pathology. Furthermore, because of the similarities between physiological and genetic systems of animals and humans, animal models of the disease are critically important in understanding if and how potential new treatments for SMA might work. The Drug Discovery Assets section of our website contains more information about animal models of SMA used in the development of SMA treatments.

While the basic biology underlying SMA has been under investigation and animal models have been developed, scientists have also been working on a variety of therapeutic approaches designed to increase the production of protein from the SMN2 gene. Several therapeutic candidates arising from these studies have entered or are approaching clinical trials in humans.

What is the currently being done to support SMA research?

Investment in research by the SMA Foundation and advocacy groups: The SMA Foundation is one of the largest sources of funding for SMA research in the world. Since our inception, we have committed over $100M in basic, translational, and clinical research in this disease. See our web pages for information about our research programs and drug discovery assets. Funding for investigators has been also provided by other organizations in the US (e.g. Families of SMA, Fight SMA, Muscular Dystrophy Association) and worldwide (e.g. European Union, AFM, SMA Europe , Italian Telethon, Genoma España, and the SMA Trust). Cumulatively, these funds support investigators at world-renowned research centers, including University of Pennsylvania, The Johns Hopkins University, Columbia University, The Ohio State University, the Massachusetts Institute of Technology, University of California, University of Southern California, Arizona State University, Stanford University, and Harvard University. Research dollars are also being invested in various biotech and pharmaceutical projects to speed progress toward a treatment.

Government funding and research on SMA: At the same time, the National Institutes of Health (NIH), Centers for Disease Control and Prevention (CDC), and United States Department of Defense (DOD) have also funded research on SMA. The NIH has selected SMA as the disease target for a pilot project in translational research. The selection was based on the facts that SMA:- Offers a high probability for the development of a treatment or cure- Is relatively common- Is a devastating children’s disease - Has no current treatment Current funding for SMA research from the National Institute of Neurological Disease and Stroke (NINDS) is approximately $16M annually. For more information about the NINDS translational research project, please visit the SMA Project website.

What is Spinal Muscular Atrophy with Respiratory Distress (SMARD) and does the SMA Foundation work on this disease?

SMARD and SMA are separate diseases with distinct causes, though the two diseases are characterized by similar symptoms, such as muscle weakness and atrophy. Spinal Muscular Atrophy with Respiratory Distress (SMARD) is a rare neuromuscular disease that results from the absence of, or mutations in, the IGHMBP2 gene, whereas SMA is caused by the absence of, or mutations in, both copies of the SMN1 gene. People with SMARD usually develop initial weakness in distal muscles (muscles furthest from the center of the body, such as those in fingers and toes), unlike patients with SMA, who usually develop weakness in proximal muscles (muscles closest to the center of the body, such as those in the trunk and neck) first. SMARD is also frequently characterized by foot abnormalities and sudden respiratory failure. Although the SMA Foundation focuses solely on the development of treatments for SMN1 gene-associated SMA, there is hope that our research may lead to symptomatic therapies that would also be of help to people living with SMARD.

For additional information about and support for individuals and families with SMARD, we can recommend the following resources:

ClinicalTrials.gov for the latest information on clinical trials
The Jennifer Trust, an SMA patient advocacy and support organization. Their website contains information about SMARD
Peer-reviewed journal publications on SMARD by Grohmann et. al. (2003) and Rudnik-Schoneborn et al (2004)

What is Spinal and Bulbar Muscular Atrophy (Kennedy’s Disease), and does the SMA Foundation work on this disease?

Although Spinal and Bulbar Muscular Atrophy and Spinal Muscular Atrophy are both neuromuscular diseases and share certain symptoms, they are separate diseases with distinct causes. Symptoms of Spinal and Bulbar Muscular Atrophy, also known as Kennedy’s Disease, include muscle weakness and wasting and, occasionally, sensory and endocrine disturbances. Unlike SMA, which is caused by deletions or defects in both copies of the SMN1 gene, Kennedy’s Disease is caused by a recessive mutation on the X chromosome. Although our work at the SMA Foundation focuses solely on the development of treatments for SMN1 gene-associated SMA, there is hope that our research may lead to symptomatic therapies that would also be of help to people living with Kennedy’s Disease.

For additional information about, and support for, individuals and families with Kennedy’s Disease, we recommend the following resources:

ClinicalTrials.gov for the latest information on clinical trials.
Kennedy’s Disease Association, a patient advocacy group.
Peer-reviewed journal publications on Kennedy’s disease by Suzuki et al (2009) and Finsterer (2009).