{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T04:59:45Z","timestamp":1785387585693,"version":"3.55.0"},"reference-count":10,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"\n Background<\/jats:title>\n \n The severity of spinal muscular atrophy (SMA) is partially influenced by\n SMN2<\/jats:italic>\n copy number, although this relationship becomes less reliable at higher copy numbers. The implementation of newborn screening has led to increasing identification of presymptomatic infants with five\n SMN2<\/jats:italic>\n copies, a subgroup for which long-term clinical outcomes remain poorly defined. Consequently, treatment decisions regarding immediate intervention versus careful clinical observation remain challenging.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We describe three patients with genetically confirmed SMA (each with homozygous\n SMN1<\/jats:italic>\n deletion and five\n SMN2<\/jats:italic>\n copies).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Marked phenotypic variability was observed. Two siblings identified through family screening showed divergent clinical courses despite a shared genetic background, with one developing adult-onset proximal weakness; the other remains asymptomatic. A third patient had adolescent-onset disease progressing to severe motor impairment. These findings highlight the limited prognostic value of\n SMN2<\/jats:italic>\n copy number.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Patients with five\n SMN2<\/jats:italic>\n copies represent a clinically heterogeneous group requiring careful longitudinal monitoring. Our findings highlight the limitations of\n SMN2<\/jats:italic>\n copy number as an independent prognostic marker and illustrate the growing challenges of treatment decision-making and therapy timing in the era of newborn screening.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fneur.2026.1898311","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T04:21:11Z","timestamp":1785385271000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Spinal muscular atrophy with five SMN2 copies: Phenotypic heterogeneity and implications for newborn screening and treatment decisions"],"prefix":"10.3389","volume":"17","author":[{"given":"Olesja","family":"Parmova","sequence":"first","affiliation":[{"name":"Department of Neurology, Centre for Neuromuscular Diseases (Associated National Centre in the ERN EURO-NMD), University Hospital Brno","place":["Brno, Czechia"]},{"name":"Faculty of Medicine, Masaryk University","place":["Brno, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blanka","family":"Adamova","sequence":"additional","affiliation":[{"name":"Department of Neurology, Centre for Neuromuscular Diseases (Associated National Centre in the ERN EURO-NMD), University Hospital Brno","place":["Brno, Czechia"]},{"name":"Faculty of Medicine, Masaryk University","place":["Brno, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1086\/338627","article-title":"Quantitative analyses of SMN1 and SMN2 based on real-time lightCycler PCR: fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy","volume":"70","author":"Feldk\u00f6tter","year":"2002","journal-title":"Am J Hum Genet"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.nmd.2018.01.003","article-title":"Correlation between SMA type and SMN2 copy number revisited: an analysis of 625 unrelated Spanish patients and a compilation of 2834 reported cases","volume":"28","author":"Calucho","year":"2018","journal-title":"Neuromuscul Disord"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"e530","DOI":"10.1212\/NXG.0000000000000530","article-title":"Practical guidelines to manage discordant situations of SMN2 copy number in patients with spinal muscular atrophy","volume":"6","author":"Cusc\u00f3","year":"2020","journal-title":"Neurol Genet"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"9029","DOI":"10.3390\/ijms22169029","article-title":"The importance of digging into the genetics of SMN genes in the therapeutic scenario of spinal muscular atrophy","volume":"22","author":"Costa-Roger","year":"2021","journal-title":"Int J Mol Sci"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"97","DOI":"10.3233\/JND-190468","article-title":"Revised recommendations for the treatment of infants diagnosed with spinal muscular atrophy via newborn screening who have 4 copies of SMN2","volume":"7","author":"Glascock","year":"2020","journal-title":"J Neuromuscul Dis"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1111\/ene.14587","article-title":"Clinical and radiological profile of patients with spinal muscular atrophy type 4","volume":"28","author":"Souza","year":"2021","journal-title":"Eur J Neurol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"523","DOI":"10.3233\/JND-200534","article-title":"Measuring outcomes in adults with spinal muscular atrophy\u2014challenges and future directions\u2014meeting report","volume":"7","author":"Sansone","year":"2020","journal-title":"J Neuromuscul Dis"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1542396","DOI":"10.3389\/fneur.2025.1542396","article-title":"Spinal muscular atrophy in the era of newborn screening: how the classification could change","volume":"16","author":"Varone","year":"2025","journal-title":"Front Neurol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.nmd.2023.12.008","article-title":"270th ENMC international workshop: consensus for SMN2 genetic analysis in SMA patients 10\u201312 March, 2023, Hoofddorp, the Netherlands","volume":"34","author":"Abiusi","year":"2023","journal-title":"Neuromuscul Disord"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.ejpn.2024.08.006","article-title":"Outcomes for patients in the RESTORE registry with spinal muscular atrophy and four or more SMN2 gene copies treated with onasemnogene abeparvovec","volume":"53","author":"Tizzano","year":"2024","journal-title":"Eur J Paediatr Neurol"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1898311\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T04:21:12Z","timestamp":1785385272000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1898311\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,30]]},"references-count":10,"alternative-id":["10.3389\/fneur.2026.1898311"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2026.1898311","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,30]]},"article-number":"1898311"}}