Types of Spinal Muscular Atrophy
Spinal muscular atrophy (SMA) is a genetic disease characterized by the progressive loss of motor neurons, or nerve cells that control muscle movement. This loss causes muscle weakness and atrophy, among other symptoms.
There are several types of SMA, based on the affected gene and the patient’s age at disease onset and severity of symptoms. Knowing the type of SMA can help to predict the course of the disease and determine treatment options. However, each patient should be considered individually, as the progression and symptoms can vary within a given type.
SMA Type 0
SMA type 0 can also be referred to as prenatal SMA, as it affects a baby while still in the womb. This is the most severe form of the disease and is characterized by poor fetal movement, joint abnormalities, difficulty swallowing, and respiratory failure. It can be fatal before birth and is almost always fatal within the first year of life.
SMA Type 1
SMA type 1, also called infantile-onset SMA or Werdnig-Hoffmann disease, is the most common type of the disease. Symptoms may be present at birth or appear within the first few months of life. Infants with this type generally have hypotonia (weak muscle tone, especially in the arms and legs) and difficulty moving, eating, breathing, and swallowing. They are unable to raise their head or sit unaided. Cognition is not affected.
SMA Type 2
SMA type 2, also referred to as intermediate SMA, typically develops between 7 and 18 months of age. The earliest symptoms of this type are often developmental delays, such as difficulty in sitting independently or sitting without support. Muscle weakness is usually more apparent in the legs than the arms. Some children may have difficulty swallowing and may have an increased susceptibility to respiratory infections.
SMA Type 3
SMA type 3 can also be referred to as juvenile SMA or Kugelberg-Welander syndrome. The symptoms of SMA type 3 usually develop after the child has learned to walk unaided, but they can become noticeable at around a year old. This type can be further broken down into two subgroups based on age of onset: SMA type 3a, where symptoms begin before age 3; and SMA type 3b, where symptoms begin after age 3 and usually progress more slowly.
SMA Type 4
SMA type 4, also called adult-onset SMA, is usually diagnosed after the age of 35, although some people may have symptoms as early as their late teens. Symptoms of SMA type 4 include mild muscle weakness in the legs and hips that may progress to the arms and shoulders. Despite a set pattern of weakness, patients differ in the extent to which they are affected; most patients are usually able to walk, and only a small number of them will require wheelchair assistance.
Finkel Type SMA
Finkel type SMA appears in adulthood, usually becoming evident when a person is in their late 20s or early 30s. Symptoms are often mild to moderate, and include muscle weakness, tremors, and twitching. This type affects the proximal muscles, or those closest to the body’s middle, and is characterized by muscle cramping of the limbs and abdomen, weakness in the leg muscles, involuntary muscle contractions, and tremors.
SMA with respiratory distress syndrome (SMARD1) is generally present at birth and is characterized by muscle weakness and respiratory failure, usually beginning between six weeks and six months of life. The first noticeable signs of SMARD1 are often breathing difficulties, which are caused by paralysis of the diaphragm. Muscle weakness usually becomes apparent shortly after respiratory failure.
Spinal muscular atrophy lower extremity dominant (SMA-LED) can begin in early childhood, affecting the lower legs. It is characterized by weakness in the leg muscles, with symptoms most pronounced in the quadriceps or large muscles of the thighs. Symptoms progress slowly and typically include waddling or an unsteady walk or gait, and difficulties standing up and climbing stairs.
Kennedy’s disease, or spinal and bulbar muscular atrophy, tends to only affect men as it is caused by mutations in the AR gene, involved in testosterone signaling and located on the X chromosome. It is mainly associated with progressive, adult-onset muscle weakness and wasting in the arms and legs. This commonly results in frequent cramps, as well as leg weakness, leading to difficulty walking and increased risk of falls.
X-Linked Infantile SMA
X-linked infantile spinal muscular atrophy (XL-SMA) is a rare and severe type of SMA, which usually is diagnosed only in males at or shortly after birth. The symptoms of XL-SMA closely resemble those of SMA type 0 or type 1. Like those two types, symptoms can begin before or just after birth. XL-SMA is associated with severe and progressive muscle weakness, which especially affects the chest muscles and restricts patients’ ability to breathe.