Jewish Genetic Disease Consortium

Affected Jewish population(s):
Ashkenazi, Egyptian

Carrier frequency in the affected Jewish population(s):
1 in 41 in Ashkenazi Jews, 1 in 10 in Egyptian Jews.

Presence in other population groups:
Occurs in a wide variety of ethnic groups at a carrier frequency from 1 in 35 (Caucasian) to 1 in 117 (Hispanic).

Symptoms:
Symptoms of SMA are related to its severity and age of onset. Many of the symptoms relate to secondary complications of muscle weakness, such as difficulty sleeping, scoliosis and joint contractures. Intellectual activity is normal.

There are five types of SMA:
Type 0 (prenatal): Most severe form that begins during pregnancy. When born, symptoms include very limited ability to move with joint contractures, difficulty breathing, and difficulty swallowing. Death usually occurs before 6 months of age.
Type I (Werdnig-Hoffmann disease): Most common form of SMA. Symptoms are present at birth or begin by 6 months of age. Children cannot sit up without support and have significant difficulty breathing and swallowing. Most children die before 2 years of age without life support.
Type II (Dubowitz disease): Typically begins between 6 – 12 months of age. These children can sit without support but cannot walk or stand without help. They have poor tone and strength and often lose the ability to sit on their own by mid-teens. 70% live past 25 years of age.
Type III (Kugelberg-Welander disease): Milder form of the condition that begins between 1 year of age and adulthood. Symptoms include muscle weakness and with difficultly walking up and down stairs. Individuals can usually stand and walk on their own, but often lose that ability later in their 30’s or 40’s. Normal lifespan possible.
Type IV: Onset typically after 30 years of age with muscle weakness and tremors or twitching. Individuals are usually able to remain walking and live a normal lifespan

Age of onset of symptoms:
Depends on type. Can be as early as birth or as late as adulthood. See above.

Impact on lifespan:
Lifespan varies from early infant death to normal adult life with only mild muscle weakness. It is dependent on the severity of the disease and the age of onset. See above.

What causes the disease:
SMA is caused by a loss of specialized nerve cells, called motor neurons, in the spinal cord and the part of the brain that is connected to the spinal cord

Treatment or management:
There is no cure for SMA. Treatment with ventilators and feeding tubes help individuals live longer lives. Management is also aimed at increasing quality of life with assistive devices. There are many experimental treatments being tested including gene replacement, stem-cell replacement of motor neurons and therapies intended to increase the expression of the SMN2 gene. There are other potential drug therapies that may enhance the SMN function or compensate for its loss.

Carrier screening:
DNA analysis by blood test. 1 mutation screened for in the Ashkenazi and Egyptian Jewish populations, 90% sensitivity.

For more information:

Families of SMA (FSMA) www.fsma.org

Genetics Home Reference: http://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy