Spinal Muscular Atrophy (SMA) Copy Number Analysis, Fetal

Background information for Spinal Muscular Atrophy (SMA) Copy Number Analysis, Fetal
Characteristics: Spinal muscular atrophy (SMA) is the most common lethal genetic disease in children. It is characterized by progressive muscle atrophy and weakness, poor weight gain, restrictive lung disease, scoliosis, and joint contractures due to degeneration of lower motor neurons and brain stem nuclei.  Onset ranges from before birth to young adulthood and severity is highly variable. Individuals with SMA have no functional copies of the SMN1 gene either due to homozygous loss of SMN1 from deletion or gene conversion (95 percent) or loss of one SMN1 gene and a pathogenic sequence variant in the other (5 percent). The SMN2 gene produces a small amount of functional survival motor neuron protein compared to SMN1. An increased number of SMN2 gene copies may reduce disease severity but phenotype cannot be predicted with certainty.
Inheritance: Autosomal recessive.
Cause: Pathogenic variants in the SMN1 gene.
Variants Tested: For copy number: SMN1 (NM_000344.3) exon 7 c.840C and exon 8 c.*239G, and SMN2 (NM_017411.3) exon 7 c.840T.
Clinical sensitivity: 95-98 percent.
Methodology: Multiplex probe ligation-dependent amplification (MLPA).
Analytical sensitivity and specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. Single base pair substitutions, small deletions/duplications, regulatory region and deep intronic variants will not be detected. This test is unable to determine chromosomal phase of SMN1 or SMN2 copies.

This test was developed and its performance characteristics determined by ARUP Laboratories. It has not been cleared or approved by the US Food and Drug Administration. This test was performed in a CLIA certified laboratory and is intended for clinical purposes.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online.