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

What is SMA?

SMA is a rare and devastating genetic disease caused by a lack of a functional survival motor neuron 1 (SMN1) gene, resulting in the rapid and irreversible loss of motor neurons, affecting muscle functions, including breathing, swallowing and basic movement.

SMA leads to progressive muscle weakness, paralysis and, when left untreated in its most severe formS, permanent ventilation and death

SMA leads to progressive muscle weakness, paralysis and, when left untreated in its most severe formS, permanent ventilation and death

SMA affects as many as 1 in every 10,000 live births worldwide

SMA affects as many as 1 in every 10,000 live births worldwide

1 in 54 people carry the genetic defect for SMA

1 in 54 people carry the genetic defect for SMA

SMA can affect people of any race or gender

SMA can affect people
of any race or gender

When both parents are carriers, their baby has a 25% chance of having SMA

When both parents are carriers, their baby has a 25% chance of having SMA

IMPORTANCE OF EARLY INTERVENTION

SMA is a rare condition, yet it is the leading cause of genetic infant death. It is imperative to diagnose SMA and begin treatment, including proactive supportive care, as early as possible to halt irreversible motor neuron loss and disease progression.

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.

There are four primary types of SMA: The severity of SMA varies across a spectrum of types that each correspond to the copy number of the SMN2 gene, the “backup gene” that produces a small fraction (~10%) of functional SMN protein compared with SMN1.

Type 1 SMA PATIENTS TYPICALLY HAVE 1-2 COPIES OF SMN2

Early onset with diagnosis usually occurs in an infant's first 6 months of age with SMA Type 1.

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

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

leads to death or the need for permanent ventilation and feeding support by the age of 2 in more than 90% of cases if untreated

About 60% of SMA cases are Type 1

About 60% of all sma cases are type 1

Type 1 symptoms:

  • Difficulty breathing and swallowing
  • Poor head control
  • Worsening muscle weakness and poor muscle tone (hypotonia), leading to "floppy" or "frog-leg" posture
  • Weak cry

TYPE 2 SMA PATIENTS TYPICALLY HAVE 2-3 COPIES OF SMN2

  • Onset between 6 to 18 months of age
  • Reduced life expectancy; more than 30% will die by age 25 if untreated
  • Most will not be able to stand without support
  • They may be able to sit independently early in development, but often lose this ability by their mid-teens
  • They may experience trembling in their fingers and skeletal abnormalities, such as scoliosis and hip dislocation
  • Difficulty with feeding and breathing often develop

TYPE 3 SMA PATIENTS TYPICALLY HAVE 3-4 COPIES OF SMN2

  • Symptoms typically appear in early childhood to early adulthood
  • Individuals affected have difficulty walking, running and going up and down stairs
  • They may lose their ability to stand or walk without support over time
  • Their legs are more severely affected than their arms

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 producing adequate SMN (survival motor neuron) protein—which is critical to the survival of neurons that control our muscles. The result? A debilitating (and often fatal in its most severe forms) 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 mutated or missing SMN1 genes, he or she will develop SMA.

1 in 54 people are carriers of a defective SMN1 gene

Approximately 1 in 54 people carry the genetic defect for SMA

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 Protein

To make protein, the SMN2 gene is read (transcribed) into an RNA sequence called pre-messenger RNA, or pre-mRNA. mRNA is the "recipe" for a protein, and is read (translated) by the cell to make a specific protein, in this case SMN. Small pieces of the pre-mRNA sequence called introns are often clipped out before mature mRNA is translated 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 protein that is degraded and only ~10% of the protein product being the full-length and functional SMN protein.

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

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

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

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