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SMA Science

What is SMA?

SMA is a genetic, neuromuscular disorder that causes progressive muscle weakness, atrophy and paralysis. It is a rare disorder, affecting approximately 1 in 10,000 live births. SMA exists on the spectrum of severity, typically classified from type I to type IV. Heterogeneity of symptoms also exists, not only depending on the type of SMA but within the same type of SMA.


One thing that unites us, however, is our relentless attitude and approach to life. As the landscape of treatment options quickly changes, it is imperative that the voices of SMA community are heard loud and clear by all!


What causes Spinal Muscular Atrophy?

SMA is caused by a mutation in the Survival Motor Neuron gene (SMN1). SMN1 is in charge of making SMN protein, which is needed by your motor neurons to stay alive and keep your muscles working. People with SMA do not have a working SMN1 gene. Instead, they rely on copies we call SMN2 to make SMN protein. The bad news is, SMN2 does not make functional SMN protein to keep people alive and healthy.

Spinal muscular atrophy is inherited in an autosomal recessive pattern. Two copies of the defective gene (one from each parent) are required to inherit the disorder. Carrier parents are not affected and in the majority of cases, aren't even aware that they are carriers. Approximately one in 40 persons are carriers. SMA affects people equally across all ethnicities and genders.


SMA Type 1 (infantile), also known as Werdnig - Hoffman disease.

The most severe form of SMA manifests typically between 0 - 6 months of age. Onset tends to be quick and unexpected (look up "floppy baby syndrome"). Rapid motor neuron death causes inefficiency of the major bodily organs (especially of the respiratory system) and pneumonia-induced respiratory failure is the most frequent cause of death. Unless placed on mechanical ventilation, babies diagnosed with SMA type 1 do not generally live past two years of age, with death occurring as early as within weeks in the most severe cases. With proper respiratory support, those with milder forms of SMA Type 1 (which account for around 10% of SMA Type 1 cases), are known to live into adolescence and adulthood.


SMA Type 2 (intermediate) also known as Dubowitz disease.

The intermediate form affects 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 noticed some time between 6 and 18 months. The progress is known to vary greatly, some people gradually grow weaker over time while others through careful maintenance avoid any progression. Scoliosis may be present, and correction with a brace may help improve respiratory function. Body muscles are weakened, and the respiratory system is a major concern. Life expectancy is reduced but most people with SMA Type 2 live well into adulthood.

SMA Type 3 (juvenile) also known as Kugelberg - Welander disaease.

The juvenile form usually manifests after 12 months of age and describes people with SMA Type 3 who are able to walk without support at some time, although many later lose this ability. Respiratory involvement is less noticeable, and life expectancy is normal or near normal.

SMA Type 4 (adult onset).

The adult-onset form (sometimes classified as a late-onset SMA type 3) usually manifests after the third decade of life with gradual weakening of muscles – mainly affects proximal muscles of the extremities – frequently requiring the person to use a wheelchair for mobility. Other complications are rare, and life expectancy is unaffected.

(CAUSE)     SMN1 gene mutation    >      insufficient SMN protein     >     death of Motor Neurons     >     muscle weakness     (EFFECT)


An SMA diagnosis can only be confirmed with absolute certainty through genetic testing. A blood sample is taken and tested for bi-allelic deletion of exon 7 of the SMN1 gene which is the cause in over 95% of cases. Genetic testing will also help establish the number of SMN2 gene copies the patient has.

There are other forms of SMA which are not caused by a deficiency of SMN protein, but instead are caused by defects in different genes on different chromosomes.


The more common manifestations of the SMA spectrum that prompt diagnostic genetic testing include:

  • Progressive bilateral muscle weakness (Usually upper arms & legs more so than hands and feet) preceded by an asymptomatic period.

  • Flattening of the chest wall when taking a breath and belly protrusion when taking a breath in.

  • hypotonia associated with absent reflexes.

Managing SMA


Respiratory Care

The respiratory system is the most common system to be affected by SMA (especially Type 1 and weaker Type 2 patients) and the complications are the leading cause of death. Weakened intercostal muscles make breathing more difficult, which can cause poor oxygen levels and inadequate clearing of airway secretions. Manual or mechanical chest physiotherapy, cough assistance devices, non-invasive ventilation (BiPAP) and tracheostomy are some of the methods and devices available to help alleviate complications.


Weakened muscles can cause difficulties with feeding, jaw movement, chewing and swallowing. Individuals with SMA are at a higher risk of being over or undernourished, food aspiration, gastric reflux, constipation, vomiting and bloating. A feeding tube and gastronomy can be of great help in these cases. While the need exists for more specific research in the area of nutrition within SMA patients, some studies suggest the existence of metabolic abnormalities which can result in muscle damage, especially while fasting. It is suggested that people with SMA, especially those with more severe forms of the disease, should reduce intake of fat and choose softer foods to avoid aspiration.

Physical Therapy, Occupational Therapy and Orthopaedics

Weakened skeletal muscles can cause tight joints with limited range of movement, hip dislocations, scoliosis, osteopenia, an increased risk of fractures, and pain. A spinal fusion can be performed to relieve the pressure cause by spinal deformities on the lungs. Physical and occupational therapy, including water therapy have been found to be of great benefit to some patients with SMA.

Creativity is key in finding ways to keep children and adults active and moving as much as possible. This video is a clear example of that.

Drug Therapies

There are currently three drug therapies on the market for Spinal Muscular Atrophy: Spinraza, Zolgensma and Risdiplam.

Gene therapy drug ZOLGENSMA is a drug focused on SMN1. It works by delivering a functional copy of the defective gene, so that your body can produce adequate amounts of SMN protein. If given to infants early enough it can stop them from developing the debilitating and life threatening symptoms of SMA. It was approved in 2019 in the US to treat those below 24 months of age.

SPINRAZA is a drug focused on SMN2 (the back up genes). It is given directly to the central nervous system using an intrathecal injection. It works by boosting the production of SMN protein, but can only benefit those currently living with SMA by slowing down or stopping progression. It was approved in the US in 2016 for patients of all ages and types of SMA, though approval in other parts of the world is restricted exclusively to patients for which clinical data exists.

Risdiplam (developed in collaboration with the SMA Foundation and PTC Therapeutics) is a small molecule used to increase the amount of SMN protein made by the SMN2 gene, commonly referred to as back up genes. Risdiplam is an orally given medication that prevents motor neuron degeneration and preserves muscle function. It is a liquid taken daily by mouth or feeding tube if required. It was approved by the USA FDA on August 7th, 2020 and is safe for individuals 2 months old and up.

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