Spinal muscular atrophy (SMA) is a genetic disorder that affects the nerves (motor neurons) responsible for controlling muscle movements. In individuals with SMA, the motor neurons in the spinal cord do not function properly, leading to muscle weakness and degeneration.

Motor neurons, particularly in the anterior horn, rely on a protein called SMN (Survival Motor Neuron), which is critical for motor neuron signaling. While SMN synthesis is encoded by the SMN-1 and SMN-2 genes, the primary source of functional SMN protein is the SMN-1 gene. This is because the SMN-2 gene has a substitution of Thymine for Cytosine at exon-7. This single difference means exon-7 is often skipped during mRNA splicing, resulting in an unstable and truncated protein that is rapidly degraded.

The SMN-2 gene produces only about 10% of the functional SMN protein. Therefore, mutations or deletions in the SMN-1 gene significantly reduce the amount of SMN protein, which is crucial for motor neuron function.

SMA is an autosomal recessive genetic disorder caused by mutations or deletions in the SMN-1 gene. More than 90% of cases involve deletions. If both parents are carriers, their child has a 25% chance of being affected and a 50% chance of being a carrier. Since the SMN-2 gene becomes the only source of SMN protein, the severity of the disease varies depending on the number of SMN-2 gene copies. Higher SMN-2 copy numbers are associated with milder symptoms.

SMN-2 gene copy numbers typically correlate with SMA types as follows:

• Type 0: 1 copy
• Type 1: 2 copies
• Type 2: 3 copies
• Type 3: 3-4 copies
• Type 4: 4 or more copies

SMA is a relatively rare condition, occurring in approximately 1 in 6,000 to 11,000 live births. About 50-60% of cases are Type 1, while the incidence of Types 2, 3, and 4 is 30%, 10%, and 1%, respectively. The incidence of the most severe form, Type 0, is below 1%.

The prevalence varies in different studies but is estimated to be around 1-2 per 100,000 individuals. Although Type 1 has the highest incidence, its shorter life expectancy results in a lower proportion among living cases. The distribution among living SMA patients is approximately:

• Type 1: 14%
• Type 2: 51%
• Type 3: 35%

SMA symptoms vary based on SMN protein levels. The disease starts with denervation in alpha motor neurons in the anterior horn of the spinal cord, leading to muscle atrophy. This results in generalized weakness, loss of motor function, and ambulatory abilities. Complications include scoliosis, recurrent pneumonia, feeding difficulties, respiratory failure, and movement disorders.

The legs are more affected than the arms, and proximal muscles are more affected than distal ones. Cognitive functions are typically normal or above average in SMA patients.

1. Type 0 is a very rare and severe type of SMA with symptoms beginning prior to birth. At birth, the infant has severe weakness and difficulty breathing and feeding.
2. Type 1 (Werdnig-Hoffmann Disease): Symptoms appear before 6 months of age, often as early as the first 3 months. This is the most severe form, characterized by progressive muscle weakness, hypotonia, feeding difficulties, and respiratory distress. Most patients do not survive beyond 18 months due to complications such as respiratory failure.
3. Type 2 (Chronic Infantile Form): Symptoms emerge between 6-18 months, typically presenting as developmental delays. Patients may struggle with unsupported sitting or standing. Respiratory complications and skeletal deformities are common, and life expectancy ranges from 2 to 30 years.
4. Type 3 (Kugelberg-Welander Syndrome): Symptoms appear after 18 months and include slow progression of muscle weakness, primarily in proximal muscles. Most patients maintain walking or sitting abilities but may have difficulty climbing stairs. Life expectancy is usually normal.
5. Type 4 (Adult-Onset SMA): Symptoms begin in the 30s and resemble Type 3. It is a benign form with a normal life expectancy.

• Weakness in arms and legs
• Movement difficulties
• Muscle tremors or twitching
• Swallowing problems
• Difficulty breathing

• Techniques to aid movement and breathing
• Feeding tubes and dietary recommendations
• Surgery for spinal or joint issues