Spinal muscular atrophy (SMA) is a genetic disorder that affects motor neurons, the nerve cells in the brain and spinal cord.
This condition causes progressive muscle weakness and atrophy, impacting the ability to perform everyday activities such as walking, eating, or breathing. Recognising the symptoms of SMA is crucial for early diagnosis and access to treatments that can significantly improve quality of life. In this article, we will explore the symptoms of SMA in detail, differentiating between its various types and addressing key questions such as life expectancy and SMA in adults.
What Are the Genetic Causes of Spinal Muscular Atrophy (SMA)?
SMA is caused by a mutation or deletion (absence of a fragment) in the SMN1 (Survival Motor Neuron 1) gene, located on chromosome 5. This gene is responsible for producing the SMN protein, which is essential for the survival and function of motor neurons. Without sufficient SMN protein, these motor neurons weaken and eventually die, leading to the progressive muscle weakness characteristic of SMA.
We all inherit two copies of the SMN1 gene, one from each parent. To develop SMA, an individual must inherit two mutated copies of the SMN1 gene, one from each parent, meaning both parents are carriers of the mutation. SMA is inherited in an autosomal recessive manner.
Another related gene, SMN2, produces a small amount of SMN protein. The number of SMN2 gene copies can influence the severity of SMA. Individuals with more copies of the SMN2 gene tend to have a milder form of the disease, as they produce more SMN protein, although it is still insufficient to compensate for the lack of a functional SMN1 gene fully.
It’s important to note that SMA does not affect cognitive or intellectual abilities. Despite the physical challenges they face, individuals with SMA have normal intelligence and can lead fulfilling and meaningful lives with the proper support.
What Are the Symptoms Based on the Type of SMA?
SMA is classified into different types based on the age of onset and the severity of symptoms. While muscle weakness is a common symptom across all kinds, the way it presents and progresses varies. Below, we outline the symptoms according to the type of SMA:
- SMA Type 1 (Werdnig-Hoffmann): This is the most severe form and manifests within the first six months of life. Babies with SMA Type 1 experience severe muscle weakness, difficulty swallowing and breathing, and lack of head control. They often cannot achieve the ability to sit without support.
- SMA Type 2 (Intermediate): This form is typically diagnosed between 6 and 18 months of age. Children with SMA Type 2 can sit without support but cannot walk independently. They experience progressive muscle weakness, respiratory difficulties, and scoliosis.
- SMA Type 3 (Kugelberg-Welander): This form appears after 18 months, even in adulthood (adult SMA). Children with SMA Type 3 can walk independently in the early stages but eventually develop progressive muscle weakness difficulty running, climbing stairs, and getting up from the floor. The progression of the disease is slower than in Types 1 and 2.
- SMA Type 4 (Adult): This is the least common form and is diagnosed in adulthood. Symptoms include progressive muscle weakness in the limbs, tremors, and difficulty performing daily activities. Progression is slow, and life expectancy is usually normal.
What Are the Common Symptoms of SMA?
Regardless of the type of SMA, some symptoms are frequently observed. Below, we outline some of these symptoms:
- Progressive muscle weakness: This is the most characteristic symptom of SMA. It primarily affects proximal muscles, those closest to the trunk, such as the shoulders, hips, and back.
- Muscle atrophy: Loss of muscle mass is a consequence of muscle weakness and may be visible to the naked eye.
- Fasciculations: Small, involuntary muscle contractions may be visible under the skin.
- Respiratory difficulties: Weakness of the respiratory muscles can lead to frequent respiratory infections and breathing difficulties.
- Scoliosis: Abnormal curvature of the spine is common in SMA, especially in Types 2 and 3.
- Feeding difficulties: Weakness in the swallowing muscles can make feeding challenging and lead to nutritional problems.
How Is SMA Diagnosed and Detected?
An accurate and early diagnosis of SMA is crucial to initiate treatment as soon as possible and maximise its effectiveness. The diagnostic process typically involves a combination of clinical evaluations, genetic testing, and neurological studies. Below, we detail the most common methods used by specialists to diagnose SMA:
Clinical evaluation:
- The clinical evaluation is the first step in the diagnostic process. The doctor will take a complete medical history, including a family history of SMA and the progression of symptoms. During the physical examination, the doctor will assess:
- Muscle tone: The resistance of muscles to passive manipulation is observed. Babies with SMA often exhibit hypotonia or decreased muscle tone.
- Muscle strength: The patient’s ability to perform various movements against resistance is evaluated.
- Deep tendon reflexes: Reflexes in different parts of the body are examined. In SMA, these reflexes are often diminished or absent.
- Presence of fasciculations: Small, involuntary muscle contractions are checked.
- Respiratory function: Lung capacity and breathing efficiency are assessed.
- Motor development: In infants and children, motor milestones such as sitting, crawling, and walking are evaluated.
Genetic testing:
Genetic testing is the definitive test for diagnosing SMA. This test looks for mutations or deletions in the SMN1 gene, responsible for producing the SMN protein, which is essential for motor neuron survival. Different types of genetic tests for SMA include:
- SMN1 gene deletion analysis: This is the most common test and detects the absence of one or both copies of the SMN1 gene.
- SMN2 gene copy number analysis: The SMN2 gene is nearly identical to SMN1 and produces SMN protein but in smaller amounts. Determining the number of SMN2 gene copies can help predict disease severity, as more copies are associated with a milder form of SMA.
- SMN1 gene sequencing: This test is used to identify point mutations in the SMN1 gene, which are less common than deletions.
- Neurological studies:
- In addition to clinical evaluation and genetic testing, neurological studies may be conducted to complement the diagnosis and assess muscle and nerve function. Some of these studies include:
- Electromyography (EMG): This test measures the electrical activity of muscles and can help differentiate SMA from other neuromuscular disorders.
- Nerve conduction study (NCS): This test measures the speed and strength of nerve signals and can help evaluate the health of peripheral nerves.
- Muscle biopsy: In some cases, a muscle biopsy may be performed to analyse muscle tissue and confirm the diagnosis. However, this test is less common due to the availability of genetic testing.
What is the life expectancy and progress of SMA treatment?
Life expectancy in SMA varies depending on the type and severity of the disease. In the past, SMA Type 1 was often fatal before the age of two. However, advances in treatment, including new gene therapies and pharmacological treatments, have significantly improved the prognosis and life expectancy of individuals with SMA.
If you recognise any of these symptoms, seeking medical attention as soon as possible is essential. Early and accurate diagnosis is key to accessing available treatments and improving quality of life. HM Hospitals has a multidisciplinary team of specialists in neurology, neuropaediatrics, pulmonology, nutrition, rehabilitation, and genetics.
Remember: This article is for informational purposes only and does not replace medical consultation. If you have any doubts, consult a healthcare professional.
