GeneReviews updates spinal muscular atrophy diagnosis and treatment guidance
Diagnosis of spinal muscular atrophy requires identification of biallelic pathogenic variants in the SMN1 gene, according to an updated clinical resource by Prior, Leach, and Finanger. SMN2 copy number increases often modify the phenotype. The disease causes symmetric muscle weakness, greater proximally than distally, from progressive loss of anterior horn cells in the spinal cord and brain stem nuclei. Three targeted therapies are now available: risdiplam (an SMN2-directed RNA splicing modifier), nusinersen (an antisense oligonucleotide), and onasemnogene abeparvovec gene replacement therapy. A second gene replacement formulation, onasemnogene abeparvovec-brve, can be given intrathecally to patients ages 2 years and older. Treatment works best when started presymptomatically. The FDA issued black box warnings for both gene replacement products, noting the possibility of serious liver injury and acute liver failure, with close monitoring of liver function required prior to and following infusion.
Presymptomatic treatment with disease-modifying therapies can prevent development or slow progression of spinal muscular atrophy features, though degenerated motor neurons cannot be restored.
Written by the Genomes desk from the primary source linked above and checked against it. Research use only; not medical advice. Corrections: [email protected].