Spinal muscular atrophy (SMA)

Spinal muscular atrophy (SMA) is a genetic condition that affects the nerves controlling muscle movement. In someone with SMA, the motor neurons in the spinal cord do not work properly, so the messages the brain tries to send along these neurons do not reach the muscles.

As a result, the muscles become weak and, over time, waste away (atrophy). SMA can affect muscles throughout the body. The muscles in the shoulders, hips and back are often most severely affected, along with the muscles used for feeding, swallowing, breathing and coughing. When the breathing muscles are involved, a person may be more prone to pneumonia and other lung problems.

A person’s intellect and senses are not affected by SMA. About one in 6,000 babies is born with the condition, and roughly one in 40 people carries a copy of the altered gene that causes it without having the condition themselves. This is known as being a genetic carrier.

There is currently no cure for SMA, but some promising treatments are being tested in clinical trials.

Types of spinal muscular atrophy#

There is a wide range in the age of onset, symptoms and rate of progression of SMA. The condition is often classified into types 1 to 4 based on the physical milestones a person reaches. The age at which symptoms start generally indicates how severe the condition is, although the course can differ from one child or adult to the next.

Babies who have symptoms at birth tend to have the most severe form (type 1), while people whose symptoms appear in adulthood may not develop severe disability and can have a normal life expectancy (type 4).

SMA type 1#

Type 1 (also called infantile-onset or Werdnig-Hoffmann disease) begins between birth and six months of age. Symptoms include trouble breathing, swallowing and sucking, generalised muscle weakness and a weak cry. Babies with type 1 do not reach the milestone of sitting up without help, and their life span rarely exceeds two years of age.

SMA type 2#

Type 2 (intermediate SMA) begins between 7 and 18 months of age. Symptoms include muscle weakness in the arms, legs and lower torso, and weak respiratory muscles. Children with type 2 learn to sit without help but generally do not stand or walk independently. Spinal curvature (scoliosis) is often a problem and may require bracing or surgery. Although there is always a risk of respiratory complications, children with type 2 usually live to young adulthood and many live longer.

SMA type 3#

Type 3 (also called Kugelberg-Welander disease) begins between 18 months and 15 years of age and is the mildest form of childhood-onset SMA. There is weakness in the leg, hip, shoulder and arm muscles, and the respiratory muscles may be weak. Children with type 3 learn to stand and walk. Some lose the ability to walk in adolescence, while others walk well into their adult years. Life expectancy is normal, the muscles for swallowing and breathing are rarely affected, and only a small number of people eventually need wheelchair assistance.

SMA type 4#

Type 4 (adult-onset SMA) begins between 18 and 50 years of age. Symptoms are usually mild and include muscle weakness and tremor.

Other rare types#

Some very rare types of SMA are caused by changes to genes other than the SMN1 gene on chromosome 5. These include:

• changes in the DYNC1H1 gene on chromosome 14, which cause a rare form called SMA-LED that predominantly affects the leg muscles
• changes in the IGHMBP2 gene on chromosome 11, which cause an extremely rare form called spinal muscular atrophy with respiratory distress (SMARD), affecting the breathing muscles
• a change to the UBE1 gene on the X chromosome, which causes X-linked SMA

What causes spinal muscular atrophy?#

SMA is caused by a change in a gene called survival motor neuron 1 (SMN1). Everybody has two copies of the SMN1 gene, one inherited from each parent. People with SMA have a gene change in both copies.

This is known as an autosomal recessive inheritance pattern. The parents of a person with SMA each carry one copy of the changed gene. Carriers do not show signs or symptoms of the condition. For carrier parents to have an affected child, both must pass on a changed copy. If both parents are carriers, the chance of a child inheriting the condition is 25 per cent, or one in four. About one in every 40 people carries the gene variation that causes SMA.

The gene change usually involves the entire gene being missing or, occasionally, part of the gene code being altered so that it becomes inactive. The role of SMN1 in the body is to produce a protein called Survival of Motor Neuron (SMN). If this protein is not produced in sufficient amounts, motor neurons start to die. Motor neurons are nerve cells in the spinal cord that send nerve fibres to muscles throughout the body and control their movement.

Why severity varies#

The reason some people are affected much more severely than others is mainly due to another gene called SMN2. This gene also produces SMN protein, but only a small amount of the full-sized, functional version. Having extra copies of SMN2 can result in larger amounts of full-length SMN protein, which reduces the severity of the disease. As a general rule:

• people with SMA type 1 usually have one or two copies of SMN2
• most people with SMA type 2 have three copies of SMN2
• people with SMA types 3 and 4 have four or more copies of SMN2

There are exceptions, and siblings with the same number of SMN2 copies can have very different severities of SMA. Severity may also depend on levels of proteins that occur naturally in the body, sometimes called disease modifiers. Two such proteins identified so far are plastin 3 and ZPR1. People who naturally produce higher amounts of these proteins tend to have less severe symptoms, but more research is needed to fully understand this.

Complications#

Children and adults with SMA are prone to respiratory infections. In the more severe types, infections such as pneumonia are often the cause of death. Children with SMA may also have trouble feeding and require feeding through a tube. Other complications include contractures (shortening of the muscles, which restricts joint movement) and scoliosis (spinal curvature).

Treatment for spinal muscular atrophy#

There is currently no specific cure for SMA, but research is moving forward at a fast pace. Support is available so that children with SMA and their families can achieve the best possible quality of life.

Treatment is tailored to the type of SMA. For example, because children with type 1 are prone to respiratory infections and pneumonia, care focuses on maintaining lung function and health. For a child or adult with type 3 or 4, care focuses on physiotherapy to help maintain muscle strength and mobility.

A multidisciplinary team is usually needed to manage the symptoms of SMA. This may include specialists in:

• neurology
• genetics
• respiratory medicine
• gastrointestinal medicine
• palliative care
• physiotherapy
• occupational therapy
• speech and language therapy
• dietetics

Genetic counselling and SMA#

If you or your child has been diagnosed with SMA, or if it runs in your family, it may help to speak with a genetic counsellor. Genetic counsellors are health professionals qualified in both counselling and genetics.

As well as providing emotional support, they can help you understand SMA and what causes it, how it is inherited, and what a diagnosis means for your child’s health and development and for your family. They are trained to provide information and support that is sensitive to your family circumstances, culture and beliefs.

If SMA runs in your family, a genetic counsellor can explain the genetic testing options available to you and other family members. You may choose to see a genetic counsellor if you are planning a family, to find out your risk of passing the condition on, or to arrange prenatal tests.

Key points#

• SMA is an inherited condition in which the motor neurons do not work properly, causing the muscles to become weak and waste away.
• There is currently no cure for SMA, but some promising treatments are being tested in clinical trials.
• There is a wide range in the age of onset, symptoms and rate of progression of SMA.
• The age at which symptoms start generally indicates how severe the condition is.
• The course of the condition may be different for each child and adult.

Where to get help#