The packet lists SMN1, located on chromosome 5, as the associated gene; no gene-validity classification is supplied. GeneReviews states that the condition is caused by biallelic pathogenic variants in SMN1 and that it is inherited in an autosomal recessive manner. According to GeneReviews, no correlation exists between the type of SMN1 pathogenic variant and disease severity, the homozygous exon 7 deletion being observed with approximately the same frequency in all phenotypes, and modifying factors that are not fully understood are thought to contribute to variability in clinical severity. GeneReviews reports that approximately 98% of parents of an affected child are carriers of one SMN1 pathogenic variant, while about 2% of affected children have a de novo variant, most often paternal in origin. For siblings of an affected individual, GeneReviews gives an approximately 25% chance of being affected, 50% of being an asymptomatic carrier and 25% of being unaffected and not a carrier; offspring of an affected individual are obligate carriers. GeneReviews lists carrier frequencies from about 1 in 45 in people of White ancestry to 1 in 100 in people of sub-Saharan African descent, and notes that incidence can be higher where parents commonly share ancestors.

GeneReviews describes two settings for diagnosis. In the first, an abnormal newborn screening result is followed by confirmatory molecular genetic testing; newborn screening for SMA is described as primarily based on real-time PCR that detects the common SMN1 deletion on dried blood spots. The packet supplies no information on whether SMA is included in particular state screening panels. In the second, a symptomatic individual presents with findings associated with later-onset or untreated infantile-onset SMA, such as a history of motor difficulties with loss of skills, proximal weakness, hypotonia and areflexia or hyporeflexia. GeneReviews states that the diagnosis is established in a proband with a history of motor difficulties or regression, proximal muscle weakness, reduced or absent deep tendon reflexes and evidence of motor unit disease, and/or biallelic pathogenic or likely pathogenic variants in SMN1 identified by molecular genetic testing. Confirmatory testing is described as typically beginning with deletion/duplication analysis of SMN1 exon 7, followed by SMN1 sequence analysis when one copy is present; findings of variants of uncertain significance neither establish nor rule out the diagnosis. A multigene panel is described as an alternative approach in symptomatic individuals.

Per GeneReviews, there is currently no cure for SMA. The packet lists three FDA-approved treatments with active market status. Risdiplam (Evrysdi) is an oral small-molecule splicing modifier approved under an NDA from CDER on 2020-08-07. Nusinersen (Spinraza) is an antisense oligonucleotide approved under an NDA from CDER on 2016-12-23; GeneReviews notes that its side effects are primarily related to its mode of delivery by lumbar puncture. Onasemnogene abeparvovec-xioi (Zolgensma) is a gene therapy approved under a BLA from CBER on 2019-05-24, delivered as a one-time intravenous injection; GeneReviews notes an FDA boxed warning for serious liver injury and acute liver failure. GeneReviews states that these three targeted options have a positive effect on disease progression and on the natural history of SMA, particularly when treatment begins before symptom onset. Orphan-drug records in the packet include branaplam, listed as withdrawn, and pegylated insulin-like growth factor 1, listed as designated; designation is not approval. GeneReviews describes initial evaluation in a multidisciplinary clinic covering growth, feeding and swallowing, respiratory function including airway clearance and sleep assessment, orthopedic and rehabilitation needs such as contractures, hip dislocation and scoliosis, genetic counseling and family support. For surveillance, GeneReviews states that individuals with SMA are evaluated at least every six months, with weaker children evaluated more often, and that visits assess nutritional state, respiratory function, motor function and orthopedic status. It also identifies prolonged fasting as a circumstance of concern in the acutely ill infant with SMA.

The packet's natural-history information comes from GeneReviews, which describes outcomes with supportive care only. For the type II phenotype, onset is listed at 6 to 18 months, the maximum motor function typically achieved is independent sitting when placed, and 70% of individuals are listed as alive at age 25 years. GeneReviews cautions that newly approved treatment options are changing the natural history of SMA phenotypes and blurring the boundaries between them, so these figures describe the supportive-care-only course and do not predict the course for any individual. Outcomes differ between individuals.

GeneReviews states that a number of therapeutic approaches are in development, including further studies of the approved therapies, splicing-directed approaches, and SMN-independent molecules aimed at increasing muscle strength; it points to the SMA drug pipeline maintained by Cure SMA. Trial records supplied in the packet include: NCT07047144, a phase 2 study of apitegromab in subjects under 2 years old with SMA, sponsored by Scholar Rock, recruiting, 2025-09-15 to 2029-03-01; NCT04042025, a phase 3 long-term follow-up study of onasemnogene abeparvovec-xioi, sponsored by Novartis Gene Therapies, active but not recruiting, 2020-02-10 to 2035-12-31; NCT05626855, a phase 3 long-term safety and efficacy study of apitegromab, sponsored by Scholar Rock, active but not recruiting, 2023-04-17 to 2029-05-02; and NCT05901987, a phase 1 gene therapy study in SMA type 2 sponsored by GeneCradle Inc, active but not recruiting, 2023-08-01 to 2028-12-01. One further supplied record, whose completion date has passed, is not described. No patient organizations are supplied in the packet.