Should we screen and treat forms of SMA with four copies of the SMN2 gene ?

Spinal muscular atrophy (SMA) is the second most common neuromuscular disorder in children. There are 3 types (from I to III) depending on the age of onset of symptoms and the maximum functional abilities reached. Recently, innovative curative therapies have emerged, whether it is nusinersen (Spinraza®), onasemnogene abeparvovec-xioi (Zolgensma®) or risdiplam™… As numerous studies have shown, these treatments are all the more effective when implemented very early, de facto raising the question of large-scale neonatal screening for SMA. Such screening programs have been implemented in a few countries including the United States, Germany, Taiwan and Belgium, and guides to good practice have been produced to help clinicians in their treatment choices.

In an article published in February 2020, clinicians in charge of neonatal screening for SMA in Germany report their experience in 279,000 newborn babies tested in 22 months, focusing on positive cases whose genotype included, in addition to the homozygous deletion of the SMN1 gene, four copies of the paralog gene SMN2. This case proved to be frequent with 15 children concerned out of the 38 screened in total. In accordance with existing recommendations, none of these newborns screened with four copies were treated immediately. However, one of them became symptomatic at the age of 8 months.The authors stress the difficulties of monitoring these complex cases and the necessary support for families. They also plead for a review of the recommendations to avoid loss of opportunity for some of these children.


Infants Diagnosed with Spinal Muscular Atrophy and 4 SMN2 Copies through Newborn Screening -Opportunity or Burden? Müller-Felber W, Vill K, Schwartz O, Gläser D, Nennstiel U, Wirth B, Burggraf S, Röschinger W, Becker M, Durner J, Eggermann K, Müller C, Hannibal I, Olgemöller B, Schara U, Blaschek A, Kölbel H. J Neuromuscul Dis. 2020 Feb 29.