August is typically one of the hottest months of the year, so today is an excellent time to stay indoors in the air conditioning and read a blog. The topic of this one is a genetic disorder called spinal muscular atrophy (SMA) that primarily affects infants and children and, more rarely, adults. August is Spinal Muscular Atrophy Awareness Month. 

SMA is a neuromuscular disorder. It is a progressive disease that destroys motor neurons, the nerve cells that control muscle movement. With SMA, motor neurons in the spinal cord are affected. As a result, the muscles begin to waste away, or atrophy. Over time, this takes away a person’s ability to walk, eat or breathe.

Approximately one in every 6,000 to 10,000 babies worldwide is born with SMA. It is generally believed that as many as 25,000 American children and adults have SMA, which is the leading genetic cause of death in infants and toddlers. It is estimated that more than 75 million Americans are carriers of the mutated gene that leads to SMA. That’s nearly one in every 40 people.

In almost all cases, SMA is caused by the insufficient production of a protein necessary for motor neuron function called survival motor neuron (SMN). SMN is primarily produced by the SMN1 gene located on chromosome 5. The SMN2 gene also produces SMN but in smaller quantities.

In children who have SMA, both of their SMN1 genes are mutated or missing, and their SMN2 genes don’t make enough SMN to compensate. Without adequate SMN, the motor neurons in the spinal cord begin to wither and die, leading to debilitating and sometimes fatal muscle weakness.

Some forms of SMA are not linked to SMN1, chromosome 5 or SMN deficiency. These forms of SMA vary greatly in severity and in the muscles affected. SMN-related SMA primarily affects the proximal muscles, those closest to the center of the body. Other forms primarily affect the distal muscles, those farthest away from the body’s center.

SMA is inherited in an autosomal recessive pattern, which means that both copies of the SMN1 genes in each cell must be mutated. To inherit SMA, both parents must carry the mutated gene and pass it along to their children. When both parents are carriers of the mutated gene, a child has a 25 percent chance of being born with SMA.

In SMN-related SMA, there is wide variability in age of onset, symptoms and rate of progression. To account for the differences, SMA is classified into four types. The age at which SMA symptoms begin roughly correlates with the degree to which motor neuron function is affected. The earlier the age of onset, the greater the impact on function.

Type I SMA, also called Werdnig-Hoffmann disease, is a severe form with muscle weakness evident at birth or within the first few months. Most children with type I SMA cannot control their head movements or sit without help. They often have swallowing problems, which cause feeding difficulties that ultimately impair growth. They also experience breathing problems. Most children with type I SMA don’t survive past early childhood due to respiratory failure.

Children with type II SMA, also called Dubowitz disease, develop muscle weakness between the ages of 6 and 12 months. While those with this type can often sit on their own, they typically cannot stand or walk unaided. They often have tremors, scoliosis and respiratory muscle weakness that can be life-threatening. Still life expectancy for children with type II SMA can range from early childhood to adulthood, depending on the severity of the patient’s condition.

Type III SMA, also called Kugelberg-Welander disease, is a mild form of the condition. Symptoms can appear anywhere from 18 months to early adulthood. Those with this type learn to stand and walk, but often lose these abilities later in life. They generally experience mild muscle weakness and are at high risk for respiratory infections. Most people with this type have near-normal life expectancies.

Type IV, or adult-onset SMA, is rare and generally does not present until people are in their 20s or 30s. People with this type of SMA can walk throughout life but typically experience mild to moderate muscle weakness, tremors and mild breathing problems. People with type IV SMA have a normal life expectancy.

SMA is typically diagnosed using a blood test that looks for the SMN1 gene. The doctor will recommend this blood test if your child’s symptoms and diagnostic workup suggest SMA. The doctor may also order an electrical study called electromyography (EMG) or a muscle biopsy to confirm the SMA diagnosis.

In July 2018, SMA screening was added to the Recommended Uniform Screening Panel for newborns. This helps ensure that every newborn baby is screened for SMA, which permits early access to life-changing and even life-saving interventions.

Currently, there is no cure for SMA. Treatment focuses on easing symptoms, preventing complications and improving quality of life. Treatments used are based on the type of SMA, the severity of the condition and your child’s age. They can range from feeding and breathing tubes to orthopedic braces, wheelchairs and physical and occupational therapy.

In December 2016, nusinersen (Spinraza) was approved by the FDA for treating all four types of SMN-related SMA in children and adults. Spinraza may be effective at slowing, stopping or possibly reversing SMA symptoms. Then in May 2019, the FDA approved Zolgensma, the first gene replacement therapy for a neuromuscular disease. Research on additional treatments for SMA is ongoing.