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Spinal Muscular Atrophy (SMA) Testing
Test Mnemonic: SMAGEN | CPT Codes: 81401, G0452 | Turnaround Time: 4-7 days
In March 2017, the American College of Obstetricians and Gynecologists (ACOG) updated their genetic carrier screening recommendations to include screening for spinal muscular atrophy.
ACOG now recommends that all women who are pregnant or considering pregnancy be offered both cystic fibrosis (CF) and spinal muscular atrophy (SMA) carrier screening.
Beginning October 25, Cleveland Clinic Laboratories will offer genetic testing for spinal muscular atrophy (SMA).
What is Spinal Muscular Atrophy?
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease that damages the nerve cells that interact with muscles.
The estimated incidence of SMA is 1 in 6,000 to 1 in 10,000 live births, and a carrier frequency of 1/40 – 1/60.
Because of its variability, SMA has been categorized into clinical subtypes:
Type 0:
Most severe type; affects babies even before they are born.
Type I:
Most common type; muscle weakness begins in the first year of life and causes a shortened life expectancy.
Type
II and III:
Both affect children, but the age of onset and severity are more variable.
Type IV:
Mildest type, with muscle symptoms starting in adulthood.
Who is At Risk For Spinal Muscular Atrophy?
1-2% of healthy people from all ethnicities are carriers for spinal muscular atrophy. Most carriers have no family history of SMA, and may be unaware that they are at risk of having a child with SMA.
In most cases, SMA carriers have only one copy of the SMN1 gene, while the second copy is deleted (1+0). The SMN1 gene, if mutated, can cause SMA.
SMA has autosomal recessive inheritance, i.e., if two SMA carriers have a child, there is a 1 in 4 (25%) chance that the child will have SMA.
What Causes Spinal Muscular Atrophy?
SMA is a genetic condition caused by changes in the SMN1 gene. Most people have 2 or 3 copies (1+1 or 1+2) of the SMN1 gene; SMA is caused when a person has zero working copies of the SMN1 gene.
In 95% of those affected by SMA, both copies of the SMN1 gene are deleted (0+0).
In the other 5% of patients, a copy of SMN1 is present, but has a small change, known as a mutation or variant, that prevents it from working properly (1d+0). Copy number testing cannot detect these small changes.
Non-Carrier Genotypes
Non-carriers have 2 or 3 copies
(1+1 or 1+2) of the SMN1 gene.
Carrier Genotypes
SMA carriers usually have one copy of SMN1, with the second copy deleted. Some carriers have two SMN1 copies on the same allele.
How Does the Spinal Muscular Atrophy Test Work?
SMA testing assesses SMN1 and SMN2 gene copy numbers, and may be used for carrier screening or as a diagnostic confirmation in a patient with clinical features of SMA.
SMA Carrier
– In healthy people, having only 1 copy of SMN1 means the person is a SMA carrier. The carrier’s partner should then have SMA testing performed to determine the couple’s chances of having a child with SMA.
– People with 2 or more copies of the SMN1 gene are unlikely to be SMA carriers, but there is still a small (less than 1%) residual risk.
SMA Diagnosis
– A diagnosis of SMA is confirmed if a patient with muscle weakness has zero copies of SMN1.
– If a symptomatic person has 1 SMN1 copy, their doctor may consider sequencing the SMN1 gene to determine if they have a small change in the copy that prevents it from working properly.
– In a person with muscle weakness, having 2 SMN1 copies means it is unlikely that SMA is the cause of their symptoms.
Why is Testing Recommended?
Both the American College of Obstetricians and Gynecologists and the American College of Medical Genetics and Genomics recommend SMA carrier screening for those who are considering pregnancy, or for those who are pregnant and have not been previously tested.
Prenatal testing allows parents to be prepared for the birth of a child with SMA, which can be critical for effective treatment options.
Genetic testing is critical in preparing for and managing a successful pregnancy.
Are You Interested in Being Screened?
If you are considering pregnancy, or are pregnant and have not been previously tested, talk to your healthcare provider about carrier screening.
Important Facts about SMA:
- Carriers do not have the disease, but can potentially pass it on to their offspring. Approximately 1 in 50 individuals are carriers of the SMN1 mutations that can lead to SMA in their children. If that person’s partner is also a SMA carrier, there is a risk of having child with SMA.
- 1-2% of healthy people from all ethnicities are carriers for SMA. Most carriers have no family history of SMA, and may be unaware that they are at risk of having a child with the disease.
- SMA testing reveals most carriers; however, even with a normal test result, there remains a small chance that you could be a SMA carrier. It is vital that you tell your doctor if someone in your family has SMA or is a carrier.
How Do I Know If My Insurance Covers Testing?
Prior to testing, call your health insurance provider and ask if the following CPT codes are covered under your insurance plan:
- 81401, G0452
How Should I Prepare For Testing?
This test requires one vial of blood to be drawn by a phlebotomist. This is a routine blood test that does not require any special preparation.
Where Can I Get My Blood Drawn?
Your doctor may be able to collect a blood sample at their office, or you may need to go to a laboratory draw site facility to have your blood drawn.
If you need to go to a different location, Cleveland Clinic Laboratories has over 30 laboratory draw stations across Northern Ohio.
Please note: if you are not a Cleveland Clinic patient, call your health insurance provider to see if CCL phlebotomy services will be covered.
How Can I Order This Test for My Patients?
Test Requisition
To order an SMA Carrier Screen or Diagnostic Test for your patient, please download and complete the Molecular Genetics Carrier Screen & Diagnostic Requisition.
Technical Information
Our Spinal Muscular Atrophy Testing Technical Brief provides a summary of the key elements of this test, including clinical significance and indications, interpretation of results, methodology, and specimen requirements.
Ordering Assistance
If you have any questions or need assistance, please contact Client Services.
Our representatives are available 24 hours a day, seven days a week to answer questions about sample collection, shipping and transportation, and test codes required for SMA testing.
You can reach Client Services at 800.628.6816 or clientservices@ccf.org.
