Spinal Muscular Atrophy
Gene: SMN1
Protein: survival motor neuron protein
Clinical Characteristics
- Progressive, symmetric proximal muscle weakness
- Respiratory failure
- Muscle atrophy due to degeneration of lower motor neurons of the spinal cord and lower brainstem
- Spectrum of phenotypes with age of onset ranging from prenatal to adulthood:
- Prenatal:
- Athrogryposis multiplex congenita
- Minimal facial weakness
- Onset prior to 6 months - SMA type I:
- Werdnig-Hoffmann disease
- Absent reflexes
- Able to sit with support
- Tongue fasciculations
- Mild contractures of large joints
- Life span typically less than 2 years
- Onset between 6 and 12 months of age - SMA type II:
- Able to sit independently when placed in a sitting position
- Postural tremor of fingers
- Life span ranges from early adulthood to normal
- Onset in childhood after 12 months of age - SMA type III:
- Able to walk independently
- Loss of ambulation in adolescence or adulthood
- Normal life expectancy
- Adult onset - SMA type IV:
- Achieve typical motor milestones
- Onset of muscle weakness in second or third decade of life
- Normal life expectancy
- Prenatal:
Inheritance pattern: Autosomal recessive
What Can Be Learned From This Test
Deletion Testing
In approximately 95% of cases, SMA is caused by homozygous deletion of SMN1. Deletion testing is performed to detect the presence or absence of SMN1. This test does not detect heterozygous carriers of an SMN1 deletion.
Indications: Confirm or rule out a suspected diagnosis of SMA.
Sequencing
About 5% of the time, SMA is caused by a deletion of SMN1 on one allele in combination with an intragenic mutation on the other allele. Gene sequencing can be performed for individuals who test negative by deletion testing. The entire coding regions of SMN1 and SMN2 are sequenced. Large duplications and deletions within the gene may not be detected.
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- Confirm or rule out a suspected diagnosis of SMA after negative deletion testing (deletion testing must be completed prior to the sequencing test, either in our lab or another facility)
- Carrier testing in an adult for a known familial intragenic mutation
Please note: Our lab does not offer sequence analysis for general population carrier screening.
Sensitivity
SMN1 is the only gene known to be associated with this form of SMA. These assays will detect mutations in greater than 99% of individuals with this form of SMA. There are other disorders that include muscular atrophy and loss of lower motor neurons. A negative SMN1 test does not rule out a genetic cause of muscle weakness, and additional testing may be indicated.
Sample Requirements
Draw 2ml–4ml of blood in EDTA/purple-top tube (minimum of 1ml–2ml for infants).
Turnaround time:
- Deletion testing: 7-10 business days
- Dosage analysis: 7-10 business days
- Sequence analysis: 10-14 business days
CPT Codes and Cost
Deletion Testing
- Code: 81329
- Cost: $425
Familial Deletion Testing
- Code: 81329
- Cost: $425
Dosage Analysis
- Code: 81329
- Cost: $475
Familial Dosage Testing
- Code: 81329
- Cost: $475
Full Gene Sequencing
- Code: 81336
- Cost: $900
Known Variant Testing
- Code: 81337
- Cost: $225