Study Highlights Importance of Swift SMA Diagnosis Through Use of Newborn, Carrier Screening

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A new study is underscoring the importance of diagnostic testing for patients with spinal muscular atrophy (SMA) to ensure early diagnosis of the disease.

A new study is underscoring the importance of diagnostic testing for patients with spinal muscular atrophy (SMA) to ensure early diagnosis of the disease.

According to the study researchers, both newborn screening (NBS) and carrier screening offer opportunities for early and prompt diagnosis for SMA, which they say is crucial, as the SMA market has seen 2 new approvals in recent years.

“Prenatal carrier testing of parents as well as newborn screening can identify the vast majority of people with SMA before onset of symptoms,” explained the researchers, who outlined the current landscape of both screening methods.

Newborn Screening

Drawing on the 2018 decision by the FDA to add SMA to the recommended universal screening program, the researchers explained that as of September 2019, 10 states had adopted and implemented NBS of SMA while 18 more states have adopted but not yet implemented such screening. Another 3 states have piloted the screening.


Such screening has demonstrated a 100% positive predictive value, with no reported false positives.

“It is estimated that universal adoption of NBS for SMA will identify 364 patients annually, 196 of whom will be type 1 patients,” wrote the researchers. “It is further estimated that such early identification will prevent approximately 50 patients from ventilator dependence and 30 deaths annually.”

According to the researchers, there are ongoing conversation on whether to incorporate carrier status in existing NBS programs, which carries an estimated cost of $0.10 to $1.00. Identified challenges in this incorporation include ensuring availability of SMA specialists and safeguarding sustainable support.

However, the researchers noted that current NBS only identifies homozygous deletions of SMN1. Although this detects 95% of infants with SMA, 5% of patients go unidentified due to having a heterozygous deletion and pathogenic sequence variant.

Carrier Screening

Three years ago, in 2017, the American College of Obstetricians and Gynecologists announced its recommendation that all women who are already pregnant or considering pregnancy be screened for carrier status, and if they test positive, their partner also be tested.

Approximately 1 in 54 in the United States is an SMA carriers, with Caucasians being the most heavily impacted and Hispanics being the least impacted.

While testing for carrier status differs between labs, next-generation sequencing is often used for gene analysis, as well as confirmatory methods, such as Sanger sequencing, if a pathogenic deletion or variant is detected.

“A large limitation to testing for carrier status is determining if the SMN1 copies are cis or are in trans,” noted the researchers. “Silent carriers, or 2+0 carriers, comprise 3.7% of SMA carriers. A silent carrier is an individual who has 2 SMN1 copies in cis, and current technologies are unable to detect because it cannot identify the haplotype phase. Therefore, the residual risk for carrier statis is higher upon a negative carrier screen or a carrier screening result identifying 2 copies of SMN1.”

The researchers offered testing for single nucleotide polymorphisms (SNPs) that are known to co-occur when 2 SMN1 copies are in cis as a means to further lower the residual risk of carrier status. However, not all carrier screening tests, which are commonly performed as part of a commercial panel including other autosomal recessive inherited genetic disorders, offer information on the status of such SNPs.


Brandsema J, Gross B, Matesanz S. Diagnostic testing for patients with spinal muscular atrophy. Clin Lab Med. 2020;40(3):357-367. doi:10.1016/j.cll.2020.05.005