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School performance of children with neurofibromatosis 1: a nationwide population-based study

European Journal of Human Genetics volume 30, pages 1405–1412 (2022)Cite this article

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Abstract

Children with neurofibromatosis 1 (NF1) may have a high burden of somatic disease and cognitive impairments, which can lead to poor academic performance. We evaluated school grades from exams ending mandatory schooling (usually around age 15 or 16 years) of children with NF1 in a population-based registry study using a within-school matched design. The study included 285 children with NF1 and 12,000 NF1-free peers who graduated from the same school and year during 2002–2015. We estimated overall and gender-specific grades by subject and compared the grades of children with NF1 with those of NF1-free peers in linear regression models. We also examined the effect of social and socioeconomic factors (immigration status and parental education, income and civil status) on grades and age at finalizing ninth grade. School grades varied considerably by socioeconomic stratum for all children; however, children with NF1 had lower grades by an average of 11–12% points in all subjects. In the adjusted models, children with NF1 had significantly lower grades than their NF1-free peers, with largest negative differences in grades observed for girls with NF1. Finally, children with NF1 were 0.2 (CI 0.1–0.2) years older than their peers on graduating from ninth grade, but only maternal educational modified the age at graduating. In conclusion, students with NF1 perform more poorly than their peers in all major school subjects. Gender had a strong effect on the association between NF1 and school grades; however, socioeconomic factors had a similar effect on grades for children with NF1 and their peers.

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Fig. 1: Effect modification of social and socioeconomic factors on overall school grades in ninth grade with 95% CIs.
Fig. 2: Effect modification of social and socioeconomic factors on age at finishing ninth grade with 95% CIs.
Fig. 3

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Data availability

All data are stored on a secure platform at Statistics Denmark (www.dst.dk/en) and can only be accessed remotely. The study group welcomes collaboration with other researchers. Study protocols can be planned in collaboration with us, and the data can be analysed accordingly at the server of Statistics Denmark. Access to data can only be made available for researchers who fulfil Danish legal requirements for access to personal sensitive data. Please contact Professor Jeanette Falck Winther (jeanette@cancer.dk) or senior researcher Line Kenborg (kenborg@cancer.dk) for further information.

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Acknowledgements

We gratefully dedicate this paper to the respected memory of Dr Sven Asger Sørensen, MD, DMSc (1936–2021). In the mid-1980s, he began the recontact and updating of a Danish national register of neurofibromatosis patients first assembled in the 1940s by A. Borberg. Dr Sørensen’s great contribution to the NF research made our current work feasible and possible.

Funding

The study was supported by a grant from the Leo Foundation, under award no. LF-OC-19-000088. The funder of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report.

Author information

Authors and Affiliations

  1. Childhood Cancer Research Group, Danish Cancer Society Research Center, Copenhagen, Denmark

    Karoline Doser, Jeanette F. Winther & Line Kenborg

  2. Statistics and Data Analysis, Danish Cancer Society Research Center, Copenhagen, Denmark

    Federica Belmonte & Klaus Kaae Andersen

  3. Center for Rare Diseases, Aarhus University Hospital, Aarhus, Denmark

    John R. Østergaard, Mette M. Handrup & Cecilie Ejerskov

  4. The RAREDIS Database, Center for Rare Diseases, Copenhagen University Hospital and Aarhus University Hospital, Aarhus, Denmark

    Hanne Hove

  5. Department of Pediatrics, University of Oklahoma, Oklahoma City, Oklahoma, USA

    John J. Mulvihill

  6. Department of Clinical Medicine, Faculty of Health, Aarhus University and University Hospital, Aarhus, Denmark

    Jeanette F. Winther

Authors
  1. Karoline Doser
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  2. Federica Belmonte
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Contributions

KD conceived and designed the study, coordinated data analysis, drafted the initial manuscript, and reviewed and revised the manuscript. FB carried out the analyses, interpreted results, and reviewed and revised the manuscript critically for important intellectual content. KKA conceived and designed the study, carried out data collection and the initial analysis, and reviewed and revised the manuscript critically for important intellectual content. JM conceived and designed the study and reviewed and revised the manuscript critically for important intellectual content. JØ, HH, MMH, CE interpreted results and reviewed and revised the manuscript critically for important intellectual content. LK and JFW conceived and designed the study, coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content. All the authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Line Kenborg.

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Competing interests

The authors declare no competing interests.

Ethics approval

The study is part of the NF1 research program ‘Life with NF1’, which was originally approved by the Danish Protection Agency (Record 2014–41–2935). With reference to the EU General Data Protection Regulation (GDPR), the research project is listed in a local database (2018-DCRC-0012) at the Danish Cancer Society Research Center. The database provides an overview of ongoing research projects involving personal data under the GDPR and replaces the former notification from the Danish Data Protection Agency.

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Doser, K., Belmonte, F., Andersen, K.K. et al. School performance of children with neurofibromatosis 1: a nationwide population-based study. Eur J Hum Genet 30, 1405–1412 (2022). https://doi.org/10.1038/s41431-022-01149-z

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