5qSMA: standardised retrospective natural history assessment in 268 patients with four copies of SMN2

Research output: Contribution to journalResearch articleContributedpeer-review


  • Ludwig Maximilian University of Munich
  • Technical University of Munich
  • Innsbruck Medical University
  • Ordensklinikum Linz
  • University Hospital Schleswig-Holstein Campus Kiel
  • Kaiser Franz Josef Hospital
  • Saarland University
  • University of Bonn
  • German Society for Muscular Dystrophy (DGM)
  • Evangelisches Krankenhaus Oldenburg
  • Justus Liebig University Giessen
  • University of Duisburg-Essen
  • LK-Banden-Mödling
  • University Hospital Tübingen
  • Hannover Medical School (MHH)
  • University of Hamburg
  • University of Rostock
  • University of Göttingen
  • Ruhr University Bochum
  • Sozialpädiatrisches Zentrum
  • University of Ottawa
  • University Medical Center Freiburg
  • Ulm University
  • Martin Luther University Hospital
  • University of Münster
  • University of Würzburg
  • Cantonal Hospital St. Gallen
  • Kepler University Hospital
  • Friedrich Schiller University Jena
  • University Hospital Augsburg
  • DKD Helios Klinik Wiesbaden
  • Landeskrankenhaus Bregenz
  • Medical University of Graz
  • Klinikum Kassel GmbH
  • Klinikum Wels - Grieskirchen GmbH
  • Friedrich-Alexander University Erlangen-Nürnberg
  • German Red Cross
  • University of Salzburg


Newborn screening for 5qSMA offers the potential for early, ideally pre-symptomatic, therapeutic intervention. However, limited data exist on the outcomes of individuals with 4 copies of SMN2, and there is no consensus within the SMA treatment community regarding early treatment initiation in this subgroup. To provide evidence-based insights into disease progression, we performed a retrospective analysis of 268 patients with 4 copies of SMN2 from the SMArtCARE registry in Germany, Austria and Switzerland. Inclusion criteria required comprehensive baseline data and diagnosis outside of newborn screening. Only data prior to initiation of disease-modifying treatment were included. The median age at disease onset was 3.0 years, with a mean of 6.4 years. Significantly, 55% of patients experienced symptoms before the age of 36 months. 3% never learned to sit unaided, a further 13% never gained the ability to walk independently and 33% of ambulatory patients lost this ability during the course of the disease. 43% developed scoliosis, 6.3% required non-invasive ventilation and 1.1% required tube feeding. In conclusion, our study, in line with previous observations, highlights the substantial phenotypic heterogeneity in SMA. Importantly, this study provides novel insights: the median age of disease onset in patients with 4 SMN2 copies typically occurs before school age, and in half of the patients even before the age of three years. These findings support a proactive approach, particularly early treatment initiation, in this subset of SMA patients diagnosed pre-symptomatically. However, it is important to recognize that the register will not include asymptomatic individuals.


Original languageEnglish
Pages (from-to)2787-2797
Number of pages11
JournalJournal of neurology
Issue number5
Early online date27 Feb 2024
Publication statusPublished - May 2024

External IDs

Mendeley 7ec499c6-7866-3d16-a71d-b86038e2e060
PubMed 38409538


ASJC Scopus subject areas


  • Age of onset, Molecular therapies, Neonatal screening, Pre-symptomatic treatment, SMA, SMN2, Spinal muscular atrophy, Humans, Child, Preschool, Male, Infant, Neonatal Screening, Young Adult, Female, Registries, Adult, Retrospective Studies, Child, Infant, Newborn, Switzerland, Disease Progression, Muscular Atrophy, Spinal/genetics, Survival of Motor Neuron 2 Protein/genetics, Adolescent, Age of Onset, Austria/epidemiology, Germany

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