About infantile spinal muscular atrophy
What is infantile spinal muscular atrophy?
The spinal muscular atrophies (SMAs), are characterized by degeneration of nerve cells (motor nuclei) within the lowest region of the brain (lower brainstem) and certain motor neurons in the spinal cord (anterior horn cells) leading to muscle weakness of the truncal, and extremity muscles initially, followed by chewing, swallowing and breathing difficulties. Motor neurons are nerve cells that transmit nerve impulses from the spinal cord or brain (central nervous system) to muscle or glandular tissue.
Approximately 80 percent of individuals with SMA fall into the severe category (Werdnig-Hoffman disease or SMA1). Infants with SMA1 experience severe weakness before 6 months of age, and the patient never achieves the ability to sit independently when placed. Muscle weakness, lack of motor development and poor muscle tone are the major clinical manifestations of SMA1. Infants with the gravest prognosis have problems sucking or swallowing. Some show abdominal breathing in the first few months of life. Abdominal breathing is noted when the abdomen protrudes during inspiration. Normally, the chest expands during inspiration as the intercostal muscles (the muscles between the ribs) expand during inspiration. Abdominal breathing occurs when the intercostal muscles are weak and the diaphragm muscle is responsible for inspiration. Movement of the diaphragm (the muscle between the chest and abdomen) expands causing the abdomen to move during the inspiration cycle. Twitching of the tongue is often seen (fasciculations). Cognitive development is normal. Most affected children die before 2 years of age but survival may be dependent on the degree of respiratory function and respiratory support.
The different subtypes, SMA 0-4 are based on the age of onset of symptoms and the course and progression of the disease. SMA represents a continuum or spectrum of disease with a mild end and a severe end. SMA0 patients are extremely weak at birth, require immediate artificial ventilation and will never breathe independently. Werdnig-Hoffman disease, which is also known as spinal muscular atrophy type 1 (SMA1) or acute spinal muscular atrophy, refers to individuals who have symptom onset prior to 6 months of age. SMA 2 patients will show symptoms prior to age 1 year, will sit but never walk. SMA 3 patients (Kugelberg-Welander disease) will show symptoms after age 1, and will walk for a period of time prior to loss of motor abilities. SMA 4 patients will not develop symptoms much before age 10 years.
All the SMAs are inherited as an autosomal recessive trait. Molecular genetic testing has revealed that all types of autosomal recessive SMA are caused by disruptions or errors (mutations) in the SMN1 (survival motor neuron 1) gene on chromosome 5.
What are the symptoms for infantile spinal muscular atrophy?
SMA is classified into five types, based on the age when symptoms appear and the severity of the condition. All types of SMA are progressive, which means they tend to get worse over time.
Type 0 SMA is the rarest and most severe type.
When a baby has type 0 SMA, the condition may be detected before they’re born, while they’re still developing in the womb.
Babies born with type 0 SMA have extremely weak muscles, including weak respiratory muscles. They often have trouble breathing.
Most infants born with type 0 SMA don’t survive for more than 6 months.
Type 1 SMA is also known as Werdnig-Hoffmann disease or infantile-onset SMA. It’s the most common type of SMA, according to the National Institutes of Health (NIH).
When a baby has type 1 SMA, they will likely show signs and symptoms of the condition at birth or within 6 months of being born.
Children with type 1 SMA typically can’t control their head movements, roll over, or sit without help. Your child may also have difficulty sucking or swallowing.
Children with type 1 SMA also tend to have weak respiratory muscles and abnormally shaped chests. This can cause serious breathing difficulties.
Many children with this type of SMA don’t survive past early childhood. However, new targeted therapies may help improve the outlook for children with this condition.
Type 2 SMA is also known as Dubowitz disease or intermediate SMA.
If your baby has type 2 SMA, signs and symptoms of the condition will likely appear between the ages of 6 and 18 months.
Children with type 2 SMA typically learn to sit on their own. However, their muscle strength and motor skills tend to decline over time. Eventually, they often need more support to sit.
Children with this type of SMA typically can’t learn to stand or walk without support. They often develop other symptoms or complications as well, such as tremors in their hands, unusual curvature of their spine, and breathing difficulties.
Many children with type 2 SMA survive into their 20s or 30s.
Types 3 and 4
In some cases, babies are born with types of SMA that don’t produce noticeable symptoms until later in life.
Type 3 SMA is also known as Kugelberg-Welander disease or mild SMA. It typically appears after 18 months of age.
Type 4 SMA is also called adolescent- or adult-onset SMA. It appears after childhood and tends to cause only mild to moderate symptoms.
Children and adults with type 3 or type 4 SMA may experience difficulties with walking or other movements, but they tend to have normal life expectancies.
What are the causes for infantile spinal muscular atrophy?
SMA is caused by mutations in the SMN1 gene. The type and severity of the condition is also affected by the number and copies of the SMN2 gene that a baby has.
To develop SMA, your baby must have two affected copies of the SMN1 gene. In most cases, babies inherit one affected copy of the gene from each parent.
The SMN1 and SMN2 genes give instructions to the body for how to produce a type of protein known as the survival motor neuron (SMN) protein. SMN protein is essential to the health of motor neurons, a type of nerve cell that passes signals from the brain and spinal cord to muscles.
If your baby has SMA, their body is unable to produce SMN proteins properly. This causes motor neurons in their body die. As a result, their body can’t properly send motor signals from their spinal cord to their muscles, which leads to muscle weakness, and eventually causes muscle wasting due to lack of use.
What are the treatments for infantile spinal muscular atrophy?
There is currently no known cure for SMA. However, multiple treatments are available to help slow the progression of the disease, relieve symptoms, and manage potential complications.
To provide the support that your baby needs, their doctor should help you assemble a multidisciplinary team of healthcare professionals. Regular checkups with members of this team are essential for managing your child’s condition.
As part of their recommended treatment plan, your child’s health team may recommend one or more of the following:
- Targeted therapy. To help slow or limit the progression of SMA, your child’s doctor may prescribe and administer the injectable medications nusinersen (Spinraza) or onasemnogene abeparvovec-xioi (Zolgensma). These medications target underlying causes of the disease.
- Respiratory therapy. To help your baby breathe, their health team may prescribe chest physiotherapy, mechanical ventilation, or other respiratory treatments.
- Nutritional therapy. To help your baby get the nutrients and calories they need to grow, their doctor or dietitian may recommend nutritional supplements or tube feeding.
- Muscle and joint therapy. To help stretch their muscles and joints, your child’s health team may prescribe physical therapy exercises. They may also recommend the use of splints, braces, or other devices to support healthy posture and joint positioning.
- Medications. To treat gastroesophageal reflux, constipation, or other potential complications of SMA, your child’s health team may prescribe one or more medications.
As your child gets older, their treatment needs will likely change. For example, if they have severe spinal or hip deformities, they may need surgery in later childhood or adulthood.
If you’re finding it emotionally difficult to cope with your baby’s condition, let your doctor know. They may recommend counseling or other support services.
Your baby’s physical therapist, occupational therapist, or other members of their health team may encourage you to invest in special equipment to help care for them.
For example, they may recommend:
- light-weight toys
- special bath equipment
- adapted cribs and strollers
- molded pillows or other seating systems and postural supports
What are the risk factors for infantile spinal muscular atrophy?
Infantile spinal muscular atrophy (SMA) is a genetic disorder that affects the motor neurons of the spinal cord. It is the most common form of SMA, and it usually appears at birth or during infancy. The first signs are often poor suckling reflexes and a weak cry, which may be followed by muscle weakness and stiffness in the arms and legs. As the disease progresses, it typically causes permanent disability.
There are three types of SMA: Type 1, Type 2, and Type 3. Each type has different symptoms, progression rates and severity levels.
The risk factors for infantile spinal muscular atrophy are still being investigated. However, there are some things that seem to be linked with the disease.
1. In most cases, infantile spinal muscular atrophy is inherited from one or both parents. If a parent has the gene for infantile spinal muscular atrophy, there's a 25% chance that any child will inherit it.
2. Some studies have shown that certain environmental factors can increase your risk of getting this disease too. For example, if someone in your family smokes cigarettes or drinks alcohol during pregnancy, you may be more likely to get it than other people who don't smoke or drink while pregnant.
3. Your child's risk of getting infantile spinal muscular atrophy depends on whether they have inherited the gene from their parents—not on how well they are cared for or what kind of environment they live in as an infant or child.
Trouble breathing,Weakness in arms and legs (especially on one side),Poor posture due to weakness or stiffness in neck muscles,Loss of head control at birth or soon after, leading to drooling and problems swallowing food
Lack of movement or weak movement,Flaccid paralysis (weakness) or hypertonia (tight muscles),Loss of reflexes,Abnormal tone, which can range from spasticity (constant tightness) to hypotonia (weakness),Muscle waste or atrophy