Carrier Screening for Spinal Muscular Atrophy Among U.S. In Vitro Fertilization Patients

Kaylen Silverberg MD1, Jocelyn Davie MS2, Nicole Faulkner PhD2, Valerie Greger PhD2, Dana Neitzel MS2
1 Texas Fertility Center, Austin TX USA 2Good Start Genetics®, Inc., Cambridge, MA, USA

Background: Spinal muscular atrophy (SMA) is a recessive neuromuscular disorder that typically causes severe muscle weakness, loss of voluntary muscle control, and death by age two. Spinal muscular atrophy is caused by defects in the Survival Motor Neuron 1 (SMN1) gene. The American College of Medical Genetics and Genomics (ACMG) recommends that carrier screening for SMA be offered routinely regardless of patient ethnicity; the American Congress of Obstetricians and Gynecologists (ACOG) does not currently support this recommendation, citing a need for additional research. Here, we further investigate the frequency of carriers of this clinically severe disorder in fertility patients.

Methods: Multiplex ligation-dependent probe amplification was used to assess SMN1 copy number in 32,771 patients from fertility centers across the United States.

Results:A total of 549 carriers were identified, giving an approximate 1/60 pan-ethnic carrier frequency. The observed carrier frequencies in specific ethnic groups ranged from one in 96 in African Americans to one in 54 in the Ashkenazi Jewish.

Discussion: Carrier screening for SMA in fertility centers is becoming routine; however, many obstetricians and gynecologists follow ACOG’s recommendations and do not offer routine screening for SMA. Our analysis shows the pan-ethnic carrier frequency for SMA in the fertility population to be in line with previously reported SMA carrier frequencies¹. SMA carrier frequencies are comparable with that of cystic fibrosis (CF); however, in the majority of cases, SMA is more clinically severe than CF. ACOG does recommend screening for CF, but not for SMA. When ACOG published its SMA guideline against routine screening in 2009, factors in addition to carrier frequency were considered. Significant advances have occurred in the clinical understanding of this disorder. Additionally, many technologic improvements have occurred since then, leading to a reduced cost of testing. Given the number of patients receiving preconception carrier screening for SMA, it is likely that both clinicians and patients perceive a benefit to screening.

Conclusions: With the widespread availability of SMA screening, the benefit this testing can provide to patients, and the recent advances in testing and clinical knowledge, ACOG may consider reevaluating its decision on routine carrier screening for spinal muscular atrophy.