Human Genetics

, Volume 137, Issue 6–7, pp 543–552 | Cite as

Phenotypic and genotypic overlap between mosaic NF2 and schwannomatosis in patients with multiple non-intradermal schwannomas

  • Hildegard Kehrer-SawatzkiEmail author
  • Lan Kluwe
  • Reinhard E. Friedrich
  • Anna Summerer
  • Eleonora Schäfer
  • Ute Wahlländer
  • Cordula Matthies
  • Isabel Gugel
  • Said Farschtschi
  • Christian Hagel
  • David N. Cooper
  • Victor-Felix Mautner
Original Investigation


Schwannomatosis and neurofibromatosis type 2 (NF2) are both characterized by the development of multiple schwannomas but represent different genetic entities. Whereas NF2 is caused by mutations of the NF2 gene, schwannomatosis is associated with germline mutations of SMARCB1 or LZTR1. Here, we studied 15 sporadic patients with multiple non-intradermal schwannomas, but lacking vestibular schwannomas and ophthalmological abnormalities, who fulfilled the clinical diagnostic criteria for schwannomatosis. None of them harboured germline NF2 or SMARCB1 mutations as determined by the analysis of blood samples but seven had germline LZTR1 variants predicted to be pathogenic. At least two independent schwannomas from each patient were subjected to NF2 mutation testing. In five of the 15 patients, identical somatic NF2 mutations were identified (33%). If only those patients without germline LZTR1 variants are considered (n = 8), three of them (37.5%) had mosaic NF2 as concluded from identical NF2 mutations identified in independent schwannomas from the same patient. These findings imply that a sizeable proportion of patients who fulfil the diagnostic criteria for schwannomatosis, are actually examples of mosaic NF2. Hence, the molecular characterization of tumours in patients with a clinical diagnosis of schwannomatosis is very important. Remarkably, two of the patients with germline LZTR1 variants also had identical NF2 mutations in independent schwannomas from each patient which renders differential diagnosis of LZTR1-associated schwannomatosis versus mosaic NF2 in these patients very difficult.


Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Supplementary material

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Supplementary material 1 (PDF 1127 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Hildegard Kehrer-Sawatzki
    • 1
    Email author
  • Lan Kluwe
    • 2
  • Reinhard E. Friedrich
    • 3
  • Anna Summerer
    • 1
  • Eleonora Schäfer
    • 1
  • Ute Wahlländer
    • 4
  • Cordula Matthies
    • 5
  • Isabel Gugel
    • 6
  • Said Farschtschi
    • 2
  • Christian Hagel
    • 7
  • David N. Cooper
    • 8
  • Victor-Felix Mautner
    • 2
  1. 1.Institute of Human GeneticsUniversity of UlmUlmGermany
  2. 2.Department of NeurologyUniversity Hospital Hamburg EppendorfHamburgGermany
  3. 3.Department of Oral and Maxillofacial SurgeryUniversity Hospital Hamburg EppendorfHamburgGermany
  4. 4.KBO- Children Clinical Center MunichMunichGermany
  5. 5.Department of NeurosurgeryUniversity of WürzburgWürzburgGermany
  6. 6.Department of NeurosurgeryUniversity Hospital TübingenTübingenGermany
  7. 7.Department of NeuropathologyUniversity Hospital Hamburg EppendorfHamburgGermany
  8. 8.Institute of Medical Genetics, School of MedicineCardiff UniversityCardiffUK

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