Researchers proposed a new way of classifying patients with spinal muscular atrophy (SMA) identified through newborn screening before any symptoms appear, based on clinical signs, and published their findings in a new commentary in Brain.

Richard Finkel, MD, and Michael Benatar, MD, MS, PhD, envision 3 phases of the disease: clinically silent or premanifest SMA, which comprises individuals with SMN gene deletions or other mutations on both chromosomes who appear to be clinically normal; prodromal SMA, in which patients have subtle symptoms that are not definitive; and symptomatic SMA which compromises patients who have definite clinical findings typical of the disease.

The authors recommend against the incorporation of known biomarkers into the definition of each phase of the disease such as the amplitude of compound motor action potential, levels of pNF-H in the plasma, and the number of copies of the SMN2 gene.

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This, they say, is because some of the biomarkers, like the SMN2 gene copy number, are static even though the disease progresses, the technology quantifying some of them like p-NF-H is still evolving, and new biomarkers are emerging all the time. This means that it may not be easy to incorporate them within the existing classification system.

“Nevertheless, we recognize that each of the currently available biomarkers has prognostic value,” the authors wrote. “As such, we recommend that individuals categorized according to our proposed tripartite clinical classification, also be characterized with respect to known biomarkers.”

SMA is currently classified based on clinical phenotypes. These include a congenital form of the disease, which typically presents in utero or at birth and represents the most severe form of the disease, and an adult form, which is the mildest form of the disease.


Finkel RS, Benatar M. Pre-symptomatic spinal muscular atrophy: a proposed nosology. Brain. Published online April 16, 2022. doi:10.1093/brain/awac125