Spinal Muscular Atrophy (SMA) Testing | SMN1 Gene Analysis | Cytogenomix® Malaysia
Neuromuscular Disorder Testing

Spinal Muscular Atrophy (SMA)

Comprehensive genetic testing for SMA including SMN1 deletion analysis and carrier screening. Essential for preconception screening and diagnostic confirmation.

1:40-60 CARRIER RATE
95% DETECTION RATE
4 CLINICAL TYPES
7-10 DAYS TAT

Test Specifications

Technical details for SMA genetic testing

Test Code SMA001 (Deletion Analysis), SMA002 (Carrier Screen), SMA003 (Comprehensive)
Methodology Multiplex Ligation-dependent Probe Amplification (MLPA), Quantitative PCR (qPCR)
Genes Analyzed SMN1, SMN2 (copy number analysis)
Mutations Detected Homozygous SMN1 deletion (exons 7 and 8), heterozygous deletions for carrier detection, SMN2 copy number for severity prediction
Sample Type 3-5 mL whole blood (EDTA purple top) | Prenatal: Amniotic fluid/CVS
Turnaround Time 7-10 working days (blood) | 10-14 days (prenatal)
Reporting SMN1 copy number, SMN2 copy number, carrier status, and clinical interpretation
Genetic Counseling Pre- and post-test counseling included

Understanding Spinal Muscular Atrophy

Spinal Muscular Atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration of alpha motor neurons in the spinal cord, leading to progressive muscle weakness and atrophy. It is caused by homozygous deletion or mutation in the SMN1 gene.

Key Facts:

  • Incidence: 1 in 6,000-10,000 live births
  • Carrier Frequency: 1 in 40-60 individuals (all ethnicities)
  • Gene: SMN1 (Survival Motor Neuron 1) on chromosome 5q13
  • Modifier Gene: SMN2 copy number influences disease severity

SMA is one of the most common fatal autosomal recessive disorders and is included in ACMG recommended carrier screening panels.

SMA Inheritance

SMN1 and SMN2 Genes

The critical relationship between these nearly identical genes

SMN1
Survival Motor Neuron 1

Produces full-length SMN protein

SMN2
Survival Motor Neuron 2

Produces ~10% functional protein

SMN1: The disease-causing gene. Homozygous deletion or mutation causes SMA.
SMN2: Modifies disease severity. More copies = milder phenotype.

Clinical Classification of SMA

Correlation between SMN2 copy number and disease severity

Type 0

Prenatal onset
SMN2: 1 copy

Severe weakness in utero, decreased fetal movements, respiratory failure at birth. Very rare.

Type I (Werdnig-Hoffmann)

0-6 months
SMN2: 2 copies

Severe weakness, unable to sit unsupported, respiratory failure by age 2 years. Most common type.

Type II (Intermediate)

6-18 months
SMN2: 3 copies

Able to sit but cannot walk independently, respiratory infections, scoliosis. Survival into adulthood.

Type III (Kugelberg-Welander)

>18 months
SMN2: 3-4 copies

Able to walk independently but may lose ambulation over time, proximal muscle weakness. Normal life expectancy.

Type IV (Adult-onset)

2nd-3rd decade
SMN2: 4-5 copies

Mild proximal weakness, normal ambulation, normal life expectancy. Rare.

SMN2 Copy Number and Disease Severity

Predicting clinical outcome based on genetic findings

SMN2 Copy Number Typical Phenotype Frequency
0 copies Not viable (lethal in utero) Extremely rare
1 copy SMA Type 0/I ~5%
2 copies SMA Type I (severe) ~60%
3 copies SMA Type II/III (milder) ~30%
4+ copies SMA Type III/IV (mildest) or asymptomatic ~5%

Clinical Implication: SMN2 copy number determination is essential for prognosis and treatment decisions, especially with emerging SMN2-targeting therapies.

Carrier Frequency by Ethnicity

SMA carrier screening is recommended for all ethnicities

1:47
Caucasian
1:72
Asian
1:66
Hispanic
1:92
African American

Overall carrier frequency: Approximately 1 in 40-60 individuals regardless of ethnicity

Autosomal Recessive Inheritance

Understanding the risk for couples who are carriers

Both Parents Carriers

Carrier
Carrier
Normal
Carrier
Carrier
Affected
25% risk affected child

50% carrier, 25% unaffected

One Parent Carrier

Carrier
Normal
Normal
Carrier
Normal
Carrier
50% carrier children

No affected children

For couples where both partners are carriers, prenatal diagnosis and PGT are available to prevent affected pregnancies.

Treatment and Management Options

Emerging therapies for SMA

Nusinersen (Spinraza®)

  • Antisense oligonucleotide
  • Increases SMN2 exon 7 inclusion
  • Intrathecal administration
  • Loading doses then maintenance

Onasemnogene abeparvovec (Zolgensma®)

  • Gene replacement therapy
  • Single IV infusion
  • AAV9 vector with SMN1 gene
  • Approved for patients <2 years

Risdiplam (Evrysdi®)

  • Oral small molecule
  • SMN2 splicing modifier
  • Daily oral administration
  • For all age groups

Supportive Care

  • Respiratory support (BiPAP, cough assist)
  • Nutritional support (feeding tube)
  • Physical and occupational therapy
  • Scoliosis management

Recommended Testing Algorithm

Step-wise approach to SMA diagnosis and carrier screening

Carrier Screen
qPCR/MLPA
SMN1 Copy Number
Genetic Counseling

Note: Approximately 2-5% of SMA cases are caused by point mutations not detected by deletion analysis. Comprehensive sequencing is available for suspected cases with negative deletion testing.

Who Should Be Tested?

Guidelines for SMA carrier screening and diagnostic testing

Preconception Screening

All couples planning pregnancy (ACOG/ACMG recommends offering SMA carrier screening to all)

Symptomatic Individuals

Infants/children with hypotonia, muscle weakness, areflexia

Family History

Individuals with family history of SMA or known carriers

Prenatal Cases

Couples where both partners are carriers, for prenatal diagnosis

Frequently Asked Questions

Common questions about SMA testing

What is the difference between SMN1 and SMN2?

SMN1 produces full-length functional SMN protein. SMN2 produces only about 10% functional protein due to alternative splicing. The number of SMN2 copies modifies disease severity in individuals with SMN1 deletions.

Can SMA be cured?

Gene replacement therapy (Zolgensma) and SMN2-targeting drugs (Spinraza, Evrysdi) have dramatically improved outcomes, especially when treated presymptomatically. While not curative, these therapies significantly alter disease progression.

What is the carrier frequency in Malaysia?

The carrier frequency in the Malaysian population is approximately 1 in 50-60, similar to other Asian populations. Carrier screening is recommended for all ethnic groups.

If I'm a carrier, will I have symptoms?

Carriers are typically asymptomatic. Rarely, carriers with only one SMN1 copy may have mild muscle weakness, but this is unusual and not clinically significant.

Can SMA be detected prenatally?

Yes, prenatal diagnosis is available through CVS (10-12 weeks) or amniocentesis (15-18 weeks) when both parents are carriers. PGT for IVF cycles is also available.

What is the "2+0" carrier situation?

Approximately 2-4% of carriers have two SMN1 copies on one chromosome and zero on the other (silent carriers). These individuals are not detected by standard carrier screening and require specialized testing.

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