What is spinal muscular atrophy? 

Spinal muscular atrophy (SMA) is an inherited neuromuscular condition affecting the central nervous system, peripheral nervous system, and voluntary muscle movement. Most of the nerve cells that control muscles are in the spinal cord and, in SMA, the muscles don’t receive signals from the brain correctly as the nerves are damaged causing progressive muscle weakness and loss of movement due to muscle wasting (atrophy).

There are different forms of SMA and a wide spectrum of how severely people are affected.  The most common form of SMA is chromosome 5 (SMN-related) SMA and, due to wide variability in age of onset, progression, and symptoms, it is classified into five different types.  Broadly speaking, Type I never sit; those with Type II never walk; those with Type III walk but may lose the ability later in life and those with Type IV experience adult-onset of symptoms resulting in fatigue leading to muscle weakness.  Patients diagnosed with Type 0 generally die from respiratory failure by 6 months of age and sometimes within the first month of life.

What causes spinal muscular atrophy? 

Chromosome 5 (SMN-related) SMA (Types 0-IV), the most common form of SMA, is caused by a mutation in the SMN1 gene (survival motor neuron 1) that produces a protein in the body called Survival Motor Neuron (SMN) protein. A deficiency of this protein affects the health of the motor neurons, causing them to shrink and eventually die.  SMA is inherited in an autosomal recessive pattern, which means that for a child to be affected both parents must be carriers of the abnormal gene, and both must pass this gene on to their child.

In unaffected people, the SMN1 gene produces full length and fully functional SMN protein, but when it has mutations, insufficient levels of SMN protein are produced.  However, a neighbouring gene on chromosome 5, SMN2, also produces SMN protein and a small percentage of the protein is functional.  People can have multiple copies of the SMN2 gene (normally between 0-8 copies) and the more SMN2 gene copies a person has the more functional SMN protein is available.  The more copies of the SMN2 gene a person with SMA has, the milder the disease course is likely to be.

What are the signs and symptoms of spinal muscular atrophy?

SMA Type 0

Signs of Type 0 SMA may occur before birth.  Mother may report a decrease in foetal movement in late pregnancy and give birth prematurely.  Newborns with type 0 present with severe weakness and heart defects.

SMA Type I

Type I SMA is also called Werdnig-Hoffmann Disease. The diagnosis of this type is usually made before 6 months of age, often a lot earlier.  Usually, a baby with Type I is very ‘floppy’ and is never able to lift their head or achieve the motor milestones expected in the early months of life. They are never able to sit up unsupported.  With mechanical ventilation and feeding tubes, children with SMA Type I can survive for a number of years.

SMA Type 2

Most cases of SMA Type II are diagnosed by 15 months. Children with this type can sit unsupported when they are placed in a sitting position, although they are often unable to reach that position without help. Some children with this type may be able to stand with the aid of assistance or bracing and/or a standing frame.  People with SMA Type II are likely to experience muscle weakness on both sides of their body and difficulties in moving arms and legs.   Weak breathing muscles may leave individuals vulnerable to chest infections.

SMA Type III

Type III SMA is also known as Kugelberg-Welander Disease. It is much more variable in age of onset: diagnosis before the age of 3 is not uncommon, but some children may not show significant symptoms until adolescence. People with Type III SMA often achieve early motor milestones and can stand up on their own and walk, although it is often noticeable that they fall more frequently and have difficulty running or getting up from the floor. Most will gradually lose the ability to walk as they get older.

SMA Type IV

The symptoms of Type IV SMA begin in adulthood.  People are affected differently but symptoms can include aching muscles, numbness, cramp, fatigue and a slight shaking of the fingers and hands.  SMA Type IV progresses steadily and slowly over time causing increased muscle weakness with age.

How does the disease progress?

The severity of the disease is dependent on type and age of onset.  SMA can be a fatal disease, however, children with SMA Type II usually live to at least young adulthood and those with Type III or Type IV (or late on-set) don’t have respiratory issues and their life expectancy is not affected.