Spinal Muscular Atrophy (SMA)

CPT 81329. If reflex testing is performed, concomitant CPT codes/charges will apply.
Synonyms
  • SMN1 Copy-number Analysis
  • Arthron-ryposis Multiplex Congenita (Prenatal SMA)
  • Congenital Axonal Neurotherapy
  • Dubowitz Disease (SMA Type II)
  • Kugelberg-Welander Disease (SMA Type III)
  • Werdnig-Hoffmann Disease (SMA Type I)

Test Details

Use

Carrier testing for individuals in the general population, or individuals with a family history of SMA, or couples who are planning a pregnancy or who are already pregnant. Pediatric or adult diagnostic testing when a diagnosis of SMA is suspected. Test 452140, Prenatal Spinal Muscular Atrophy (SMA) Testing, should be used for prenatal diagnosis for at-risk pregnancies, when both parents are carriers or when severe joint contractures are found on fetal ultrasound.

Special Instructions

For prenatal testing, please refer to test code 452140, Prenatal Spinal Muscular Atrophy (SMA) Testing.

Limitations

SMN1 copy number analysis does not detect individuals who are carriers of SMA as a result of germline mosaicism; or small intragenic variants within the SMN1 gene; or variants in genes other than SMN1.

False-positive or false-negative results may occur for reasons that include genetic variants, technical handling, blood transfusions, bone marrow transplantation, mislabeling of samples, or erroneous representation of family relationships.

Methodology

The copy number of SMN1 exon 7 is assessed relative to internal standard reference genes by quantitative polymerase chain reaction (qPCR). A mathematical algorithm calculates 0, 1, 2 or 3 copies with statistical confidence. When no copies of SMN1 are detected, the primer and probe binding sites are sequenced to rule out variants that could interfere with copy number analysis and SMN2 copy number is assessed by digital droplet PCR analysis relative to an internal standard reference gene. Individuals with one copy of SMN1 are predicted to be carriers of SMA; those with two or more copies have a reduced carrier risk. For carrier screening, when two copies of SMN1 are detected, allelic discrimination qPCR targeting c.*3+80T>G in SMN1 is performed. The presence or absence of c.*3+80T>G correlates with an increased or decreased risk, respectively, of being a silent carrier (2+0).1,2

Specimen Requirements

Information on collection, storage, and volume

Specimen

Whole blood

Volume

Adults: 10 mL whole blood; 20 mL whole blood if ordering multiple tests

Container

Whole blood: Yellow-top (ACD-A) tube (preferred) or lavender-top (EDTA) tube; yellow-top (ACD-B) tube is not acceptable

Storage Instructions

Maintain specimen at room temperature.

Causes for Rejection

Frozen or hemolyzed specimen; quantity not sufficient for analysis; blood specimens more than four days post draw