WHAT YOU NEED TO KNOW ABOUT SPINAL MUSCULAR ATROPHY (SMA)

What is SMA?

SMA is a severe neuromuscular disease caused by a genetic defect in the SMN1 (survival motor neuron 1) gene. It leads to the loss of motor neurons and results in progressive muscle weakness and paralysis.

The number 1 genetic cause of infant death

Prior to the availability of effective therapies, was the number 1 genetic cause of infant death

As many as 1 in 10,000 live births are affected by SMA

As many as 1 in every 10,000
live births will be affected

1 in 50 Americans are SMA genetic carriers

1 in 50 Americans
are genetic carriers

SMA can affect people of any race or gender

SMA can affect people
of any race or gender

Untreated, survivors require lifelong care and support

Untreated, survivors REQUIRE
lifelong care and support

Be SMA aware

SMA is a rare condition, yet it is the number one genetic cause of infant death. Early diagnosis is critical in this fast-moving disease.

Signs and Symptoms of SMA
Watch this video to hear parents of children with SMA talk about the early signs and symptoms to look for to help reach a diagnosis quickly.

SMA Newborn Screening

Early detection is a powerful weapon in the fight against SMA. Hear from doctors and parents of children with SMA about why newborn screening could make a world of difference.

Watch this video to understand why the SMA community is calling for SMA to be added to the national newborn screening panel.

There are four types of SMA:

Type 1 (also called werdnig-hoffman disease) is the most severe

Early onset with diagnosis usually occurs in an infant's first 6 months

Early onset with diagnosis usually in an infant's first 6 months

90% of most severe cases face death or need permanent ventilation support by 2 years of age

90% mortality or need for permanent ventilation support by 2 years old

60% of all SMA cases are Type 1

60% of all sma cases are type 1

Type 1 symptoms:

  • Hypotonia, or “floppy baby syndrome,” is an abnormal limpness in the neck and limbs
  • Muscle weakness (particularly in the legs)
  • Poor head control
  • Abdominal breathing, also called “diaphragmatic” or “belly breathing,” is contraction of the diaphragm (rather than the chest) when breathing
  • Bulbar muscle weakness, which is exhibited by a weak cry, difficulty swallowing, and aspiration
  • Inability to sit unsupported

Type 2 (also called Dubowitz Syndrome)

  • Onset between 6 to 18 months of age
  • Reduced life expectancy; 68% alive at age 25
  • Will never be able to walk without support
  • Most will never stand without support

Type 3 (also called Kugelberg-Welander disease or juvenile SMA)

  • Onset after 18 months
  • Can be diagnosed as late as the teenage years
  • Individuals affected are initially able to walk but have increasingly limited mobility as they grow

Type 4 (Adult Onset)

  • Very rare
  • Symptoms can start as early as 18 years but usually begin after age 30
  • Mobility characteristics are similar to Type 3

The Genetics Behind SMA

Human DNA has many genes. Two genes that are involved in SMA are SMN1 and SMN2.

SMN1 GENE: INHERITABLE ODDS

Inheriting a mutated (changed) or missing SMN1 gene prevents the body from adequately producing the SMN (survival motor neuron) protein—which is critical to the nerves that control our muscles. The result? A debilitating (and often fatal) muscle weakness called SMA.

People typically receive one copy of the SMN1 gene from each parent. Only one functioning SMN1 gene is needed to produce adequate levels of the SMN protein. Since SMA is a recessive trait, even though both parents may be healthy, each can carry and hand down a mutated (changed) or missing SMN1 gene. If the child inherits both of these recessive SMN1 genes, he or she will develop SMA.

1 in 50 Americans are carriers of a defective SMN1 gene

1 in 50 Americans are carriers of a defective SMN1 gene

2 carriers have a 25% chance of having a child with SMA

Two carriers have a 25% chance of having a child with SMA

SMN2 Gene: A Secondary source of SMN

To make protein, the SMN2 gene is read into an RNA sequence called "messenger RNA," or mRNA. mRNA is the “recipe” for a protein, and is read by the cell to make a specific protein, in this case SMN. Small pieces of the mRNA sequence called introns are often clipped out before it is read to make the protein. Unfortunately, a piece that is supposed to remain, EXON 7, is inadvertently cut out of most of the mRNA strands coming from SMN2, resulting in ~90% of the protein product being an unstable, dysfunctional form of SMN and only ~10% of the protein product being the full-length SMN protein.

Up to 90% of SMN protein produced by the SMN2 gene is non-functional

Up to 90% of SMN protein produced by the SMN2 gene is non-functional

SMN2 modifies SMA severity – the more copies there are, the less severe the disease

SMN2 modifies SMA severity— the more copies there are, the less severe the disease is