Keratinocytic epidermal nevus syndrome with Schwann cell proliferation, lipomatous tumour and mosaic KRAS mutation.
BACKGROUND
Keratinocytic epidermal nevus syndrome (KENS) is a complex disorder not only characterized by the presence of epidermal nevi but also by abnormalities in the internal organ systems. A small number of cases with KENS are molecularly characterized and reported in the literature with somatic activating RAS, FGFR3 and PIK3CA mutations.


METHODS
In this study we present a patient with hyper- and hypopigmented regions, verrucous pigmented skin lesions and a paravertebral conglomerate tumour at the level of the cervical and thoracic spine. A large lipomatous dumbbell tumour caused atrophy of the spinal cord with progressive paraparesis. We identified a mosaic c.35G > A (p.Gly12Asp) KRAS mutation in the pigmented verrucous epidermal nevus tissue, the intraneural schwann cells and the lipoma. The c.35G > A (p.Gly12Asp) KRAS mutation was absent in the peripheral blood leukocytes.


CONCLUSIONS
We conclude that KENS, the intraneural Schwann cell proliferation and the lipoma in this individual were caused by a postzygotic and mosaic activating c.35G > A (p.Gly12Asp) KRAS mutation.
Department of Neurology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany. s.farschtschi@uke.de.
Said
S
Farschtschi
Department of Neurology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany. v.mautner@uke.uni-hamburg.de.
Victor-Felix
VF
Mautner
Department of Human Genetics, KU Leuven - University of Leuven, Leuven, Belgium. silke.hollants@med.kuleuven.be.
Silke
S
Hollants
Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. hagel@uke.de.
Christian
C
Hagel
Department of Human Genetics, University Hospital Leuven, Leuven, Belgium. marijke.spaepen@uzleuven.be.
Marijke
M
Spaepen
Institute for Heamatopathology, Hamburg, Germany. cschulte@hp-hamburg.de.
Christoph
C
Schulte
Department of Human Genetics, KU Leuven - University of Leuven, Leuven, Belgium. eric.legius@uzleuven.be.|Department of Human Genetics, University Hospital Leuven, Leuven, Belgium. eric.legius@uzleuven.be.
Eric
E
Legius
Department of Human Genetics, KU Leuven - University of Leuven, Leuven, Belgium. Hilde.Brems@med.kuleuven.be.
Hilde
H
Brems
D000293:Adolescent; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008067:Lipoma / Q000150:complications*; D008297:Male; D009154:Mutation; D009506:Nevus / Q000150:complications / Q000235:genetics / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012583:Schwann Cells / Q000473:pathology*; D012871:Skin Diseases / Q000150:complications / Q000235:genetics / Q000473:pathology; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics*
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins