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Open Access 01-10-2020 | Attention Deficit Hyperactivity Disorder | Annual issue paper

Clinical characterization of children and adolescents with NF1 microdeletions

Authors: Hildegard Kehrer-Sawatzki, Lan Kluwe, Johannes Salamon, Lennart Well, Said Farschtschi, Thorsten Rosenbaum, Victor-Felix Mautner

Published in: Child's Nervous System | Issue 10/2020

Abstract

Purpose

An estimated 5–11% of patients with neurofibromatosis type 1 (NF1) harbour NF1 microdeletions encompassing the NF1 gene and its flanking regions. The purpose of this study was to evaluate the clinical phenotype in children and adolescents with NF1 microdeletions.

Methods

We retrospectively analysed 30 children and adolescents with NF1 microdeletions pertaining to externally visible neurofibromas. The internal tumour load was determined by volumetry of whole-body magnetic resonance imaging (MRI) in 20 children and adolescents with NF1 microdeletions. Furthermore, the prevalence of global developmental delay, autism spectrum disorder and attention deficit hyperactivity disorder (ADHD) were evaluated.

Results

Children and adolescents with NF1 microdeletions had significantly more often cutaneous, subcutaneous and externally visible plexiform neurofibromas than age-matched patients with intragenic NF1 mutations. Internal neurofibromas were detected in all 20 children and adolescents with NF1 microdeletions analysed by whole-body MRI. By contrast, only 17 (61%) of 28 age-matched NF1 patients without microdeletions had internal tumours. The total internal tumour load was significantly higher in NF1 microdeletion patients than in NF1 patients without microdeletions. Global developmental delay was observed in 28 (93%) of 30 children with NF1 microdeletions investigated. The mean full-scale intelligence quotient in our patient group was 77.7 which is significantly lower than that of patients with intragenic NF1 mutations. ADHD was diagnosed in 15 (88%) of 17 children and adolescents with NF1 microdeletion. Furthermore, 17 (71%) of the 24 patients investigated had T-scores ≥ 60 up to 75, indicative of mild to moderate autistic symptoms, which are consequently significantly more frequent in patients with NF1 microdeletions than in the general NF1 population. Also, the mean total T-score was significantly higher in patients with NF1 microdeletions than in the general NF1 population.

Conclusion

Our findings indicate that already at a very young age, NF1 microdeletions patients frequently exhibit a severe disease manifestation which requires specialized long-term clinical care.

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Title: Clinical characterization of children and adolescents with NF1 microdeletions
Authors: Hildegard Kehrer-Sawatzki
Lan Kluwe
Johannes Salamon
Lennart Well
Said Farschtschi
Thorsten Rosenbaum
Victor-Felix Mautner
Publication date: 01-10-2020
Publisher: Springer Berlin Heidelberg
Keywords: Attention Deficit Hyperactivity Disorder
Autism Spectrum Disorder
Neurofibromatosis Type 1
Attention Deficit Hyperactivity Disorder
Published in: Child's Nervous System / Issue 10/2020
Print ISSN: 0256-7040
Electronic ISSN: 1433-0350
DOI: https://doi.org/10.1007/s00381-020-04717-0

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Clinical characterization of children and adolescents with NF1 microdeletions

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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