Spinal muscular atrophy (SMA) is a rare genetic condition characterized by the progressive loss of motor neurons, which are the specialized nerve cells that control voluntary movement, leading to muscle weakness and atrophy, among other symptoms.
There are several types of SMA, based on the affected gene, age at symptom onset, and severity of symptoms.
Knowing a patient’s SMA type can help to predict the disease’s course and determine treatment options. However, each patient should be considered individually, as disease progression and symptoms can vary within a given type.
Main types of SMA
SMA is divided into five main, common types — 0, 1, 2, 3, and 4 — based on the age of symptom onset and the highest motor milestone achieved. All of these types are caused by mutations in the SMN1 gene, which provides instructions to produce a protein essential for motor neuron and muscle health.
SMA type 0
In type 0, the most severe form of the disease, symptoms appear before birth, while still in the womb. This type is characterized by poor fetal movement and by extremely weak muscle tone (lack of tension in the muscles, which can cause floppiness) and breathing and feeding difficulties at birth. It can be fatal before birth, and almost always is fatal within the first year of life.
SMA type 1
Type 1, also called infantile-onset SMA or Werdnig-Hoffmann disease, is the most common type of SMA, accounting for 60% of cases. Symptoms usually begin in the first six months of life, and typically include muscle weakness, poor muscle tone, developmental delays, and difficulties breathing and swallowing. If disease-modifying treatment is not initiated, most of these infants do not survive past age 2, usually due to respiratory failure.
SMA type 2
In type 2, sometimes called intermediate or chronic infantile SMA, symptoms usually appear between 6 and 18 months of age. Muscle weakness and atrophy (shrinkage), as well as problems in swallowing, chewing, and breathing, are common. Children with this type of SMA may be able to sit, but may never be able to stand or walk unaided. Most children with SMA type 2 live into adulthood.
SMA type 3
Type 3, also known as juvenile SMA or Kugelberg-Welander syndrome, is a milder type of SMA, with symptoms generally being evident between 18 months and 3 years of age. Children with this type of SMA may have mild muscle weakness and be able to stand and walk, but often lose this ability as they age and require aids. They generally have an almost normal life expectancy.
SMA type 4
Type 4, or adult-onset SMA, is very rare and represents the mildest form of SMA. It generally develops after age 30, with slow progression of mild motor impairment, which typically does not affect a patient’s ability to walk. People with this type have a normal life expectancy.
Rarer types of SMA
Other types of SMA tend to be rarer and are caused by mutations in genes other than SMN1.
X-linked infantile SMA is associated with mutations in UBA1, a gene located on the X chromosome, and affects only males. It tends to progress in a way similar to SMA types 0 and 1, with symptoms starting before or shortly after birth. Symptoms include joint deformities and severe and progressive muscle weakness, which affects the ability to reach motor milestones and to breathe. These boys usually do not survive past early childhood due to respiratory failure.
SMA with respiratory distress 1 causes respiratory failure typically between the ages of 6 weeks and 6 months, followed by progressive muscle weakness that first affects the hands and feet. Unless patients receive mechanical ventilation, most affected infants will die from respiratory failure before 13 months of age. It is caused by mutations in the IGHMBP2 gene.
Spinal muscular atrophy lower extremity dominant can begin in infancy or early childhood and progresses slowly, mainly affecting the thigh muscles. Most frequent symptoms include waddling or an unsteady walk or gait, and difficulties in rising from a seated position and in climbing stairs. It is caused by a mutation in either the DYNC1H1 or BICD2 gene
SMA with progressive myoclonic epilepsy, also known as SMA plus, develops during childhood with progressive muscle weakness and atrophy, followed by a combination of seizures and uncontrollable muscle jerks during later childhood. It is caused by mutations in the ASAH1 gene.
Finkel type SMA is an adult-onset form of the disease, in which symptoms, including mild-to-moderate muscle weakness, tremors, and twitching, generally emerge after age 30. It is caused by mutations in the VAPB gene.
Kennedy’s disease, also known as spinal and bulbar muscular atrophy, mainly affects males, begins between ages 30 and 50, and is characterized by a slow progression. This type of SMA is caused by mutations in the androgen receptor (AR) gene and causes weakness not only in muscles of the arms and legs, but also in those involved in chewing, swallowing, and speaking. Testosterone deficiencies leading to infertility and other sex-related features also are common. Life expectancy is normal.
Last updated: July 28, 2021
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