Spinal Muscular Atrophy (SMA): Symptoms, Causes, Treatment

What are the symptoms of spinal muscular atrophy?

Spinal muscular atrophy (SMA) is a genetic disorder characterized by the progressive degeneration of motor neurons in the spinal cord, leading to muscle weakness and atrophy. The symptoms vary depending on the type and severity of SMA, but common signs include:

• Muscle Weakness: Progressive weakness in the muscles, particularly those involved in movement, such as the arms, legs, and trunk. In infants, this may manifest as difficulty in lifting the head or holding up the body.
• Muscle Atrophy: Wasting of muscles due to lack of use and nerve stimulation. This can lead to a noticeable reduction in muscle mass.
• Hypotonia: Decreased muscle tone or “floppiness,” often observed in infants who have trouble moving their limbs or maintaining posture.
• Difficulty with Motor Skills: Challenges with activities such as crawling, walking, or climbing stairs. This is more noticeable in later-onset forms of SMA.
• Swallowing Difficulty and Breathing Difficulties: Weakness in the muscles involved in swallowing and breathing can lead to problems with eating, increased risk of choking, and respiratory issues.
• Tremors or Twitching: In some cases, small, involuntary movements or tremors may be present.
• Curved Spine (Scoliosis): Progressive muscle weakness can lead to scoliosis, or curvature of the spine, particularly in more advanced stages.
• Decreased Reflexes: Reduced or absent reflexes, such as the knee jerk reflex, may be noted.

The severity and progression of these symptoms can vary widely, with some forms of SMA presenting in infancy with rapid progression, while others may have a later onset and slower progression. Early diagnosis and management are important for improving quality of life and outcomes for individuals with SMA.

What are the causes of spinal muscular atrophy?

Spinal muscular atrophy (SMA) is caused by genetic mutations that affect the survival of motor neurons in the spinal cord. Specifically, SMA is caused by mutations in the SMN1 gene (Survival Motor Neuron 1 gene), which is crucial for the production of a protein essential for the health and function of motor neurons.

Here’s a breakdown of the causes:

• Genetic Mutations: The primary cause of SMA is a mutation or deletion in the SMN1 gene, which results in a deficiency of the SMN protein. This protein is critical for the maintenance and survival of motor neurons. Without sufficient SMN protein, motor neurons gradually degenerate and die.
• Inheritance Pattern: SMA is inherited in an autosomal recessive pattern, meaning that a person needs to inherit two copies of the mutated SMN1 gene (one from each parent) to develop the condition. Individuals with only one mutated gene (carriers) do not show symptoms but can pass the mutation to their offspring.
• SMN2 Gene: A related gene, SMN2, can partially compensate for the loss of SMN1. However, it produces a smaller amount of functional SMN protein. The number of SMN2 gene copies a person has can influence the severity of SMA. More SMN2 copies usually result in a milder form of the disease.
• Genetic Variability: Variability in the SMN2 gene and other genetic factors can affect the onset and progression of the disease. For instance, the number of SMN2 gene copies can modify the clinical severity of SMA.

In summary, SMA is primarily caused by mutations in the SMN1 gene that lead to insufficient levels of the SMN protein, which is crucial for motor neuron survival. The autosomal recessive inheritance pattern of this condition means that both parents must carry the mutated gene for their child to develop SMA.

What is the treatment for spinal muscular atrophy?

Treatment for spinal muscular atrophy (SMA) involves a combination of strategies aimed at managing symptoms, slowing disease progression, and enhancing quality of life.

Disease-modifying therapies play a crucial role, with options such as nusinersen (Spinraza), which increases the production of the SMN protein from the SMN2 gene through intrathecal injection. Onasemnogene abeparvovec-xioi (Zolgensma) is a gene therapy that introduces a functional copy of the SMN1 gene via intravenous infusion. Another medication, risdiplam (Evrysdi), enhances SMN protein production from the SMN2 gene and is taken orally as a daily liquid.

Supportive care is also essential and includes physical therapy to maintain mobility and prevent contractures, occupational therapy to aid in daily activities, and speech therapy for communication and swallowing issues.

Respiratory support may be necessary, using non-invasive ventilation devices like CPAP or BiPAP to assist with breathing, or in severe cases, a tracheostomy for long-term support. Nutritional support ensures adequate intake, potentially involving feeding tubes if swallowing difficulties are present.

Orthopedic management may involve bracing and orthotics to support limbs and prevent deformities, with surgical interventions sometimes required for severe scoliosis or joint contractures. Regular monitoring and a multidisciplinary approach involving various specialists help to tailor the treatment plan based on individual needs and the severity of the condition. Early intervention with disease-modifying therapies can significantly improve outcomes, particularly when started before significant motor neuron loss occurs.