What are the other Names for this Condition? (Also known as/Synonyms)

• Juvenile Spinal Muscular Atrophy
• Kugelberg-Welander Syndrome (KWS)
• Spinal Muscular Atrophy, Mild Childhood and Adolescent Form

What is Spinal Muscular Atrophy Type 3? (Definition/Background Information)

• Spinal Muscular Atrophy Type 3 (SMA3), also known as Proximal Spinal Muscular Atrophy Type 3, is a relatively mild form of proximal spinal muscular atrophy, characterized by muscle weakness and hypotonia resulting from the degeneration and loss of the lower motor neurons in the spinal cord and the brain stem nuclei.
• The disorder manifests after 12 months of age (usually between childhood and adolescence), after ambulation has been acquired. Two subtypes (SMA3a and SMA3b) have been distinguished by some authors: 
• SMA3a defines patients with onset before the age of 3 years
• SMA3b defines patients with onset after 3 years
• Difficulties walking, running, and going up and down stairs are common. The muscle weakness predominantly affects the legs and hip muscles and then progresses to the shoulders and arms. Legs are always more severely affected than arms. Weak finger trembling and scoliosis are frequent and the patellar reflex is absent
• Spinal Muscular Atrophy Type 3 is primarily caused by deletions in the SMN1 gene (5q12.2-q13.3) encoding the SMN (survival motor neuron) protein. Deletions of the NAIP (5q13.1) gene, which may play a role in modifying severity of the disorder, have also been identified in SMA3 patients
• A wheelchair may be required during childhood for some patients (more commonly those with SMA3a), whilst others retain the ability to walk into adulthood (more commonly those with SMA3b)
• SMA3 progresses slowly and life expectancy is usually normal. However, deformities of the vertebral column are frequent and complications may lead to respiratory restriction

(Source: Proximal Spinal Muscular Atrophy Type 3; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Who gets Spinal Muscular Atrophy Type 3? (Age and Sex Distribution)

• Spinal Muscular Atrophy Type 3 is a rare congenital disorder. The estimated frequency of occurrence of the disorder is 1:375,000
• The presentation of symptoms typically occur after 12 months of age, when a child starts walking
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Spinal Muscular Atrophy Type 3? (Predisposing Factors)

• A positive family history may be an important risk factor, since Spinal Muscular Atrophy Type 3 is an inherited condition
• Currently, no other risk factors have been clearly identified for SMA3

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Spinal Muscular Atrophy Type 3? (Etiology)

Spinal Muscular Atrophy Type 3 is primarily caused by deletions in the SMN1 gene (5q12.2-q13.3) encoding the survival motor neuron (SMN) protein.

• Although there is some variation, the severity of the disorder in SMA is inversely correlated with the number of copies of the second SMN gene (SMN2; 5q13.2), with patients with MSA3 having three (SMA3a) or four (SMA3b) SMN2 copies
• Deletions of the NAIP (5q13.1) gene, which may play a role in modifying the severity, have also been identified in SMA3 patients 
• Spinal Muscular Atrophy Type 3 is inherited in an autosomal recessive manner

(Source: Proximal Spinal Muscular Atrophy Type 3; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Spinal Muscular Atrophy Type 3?

The signs and symptoms of Spinal Muscular Atrophy Type 3 may include:

• Areflexia of lower limbs
• Degeneration of anterior horn cells
• EMG abnormality
• Hand tremor
• Hyporeflexia
• Limb fasciculations
• Muscle cramps
• Spinal muscular atrophy
• Tongue fasciculations

(Source: Spinal Muscular Atrophy Type 3; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Spinal Muscular Atrophy Type 3 Diagnosed?

Spinal Muscular Atrophy Type 3 is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary
• Molecular genetic testing to confirm SMN1, SMN2 or NAIP gene mutation(s)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Spinal Muscular Atrophy Type 3?

The complications of Spinal Muscular Atrophy Type 3 may include:

• Respiratory distress due to abnormalities in the vertebral column
• Difficulty with walking
• Dependence on wheel chair for mobility

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Spinal Muscular Atrophy Type 3 Treated?

• There is no cure for Spinal Muscular Atrophy Type 3, since it is a genetic disorder. The treatment given is to address the signs and symptoms and any complication that may develop
• The medication listed below has been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition: Nusinersen 

How can Spinal Muscular Atrophy Type 3 be Prevented?

Presently, Spinal Muscular Atrophy Type 3 may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Spinal Muscular Atrophy Type 3? (Outcomes/Resolutions)

• The prognosis of Spinal Muscular Atrophy Type 3 is optimistic, since the disorder progresses slowly and life expectancy is usually normal. However, deformities of the vertebral column are frequent and complications may lead to respiratory restriction
• A wheelchair may be required during childhood for some patients (more commonly those with SMA3a), whilst others retain the ability to walk into adulthood (more commonly those with SMA3b)

(Source: Proximal Spinal Muscular Atrophy Type 3; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Additional and Relevant Useful Information for Spinal Muscular Atrophy Type 3:

• Spinal Muscular Atrophy Type 3 is also known by the following additional synonyms: Proximal Spinal Muscular Atrophy Type 3

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/