Abstract
Schimmelpenning syndrome is a rare neurocutaneous disorder categorized as a mosaic RASopathy due to postzygotic HRAS or KRAS mutations. We report a 6-year-old girl diagnosed with Schimmelpenning syndrome due to a postzygotic KRAS G12D mutation. The patient had three atypical symptoms of Schimmelpenning syndrome: renovascular hypertension, congenital lipomatosis, and diabetes mellitus. The first two symptoms may overlap with phenotypes of other neurocutaneous syndromes or congenital lipomatous overgrowth syndrome due to mosaic RASopathies or other somatic mosaic mutations. We propose that impaired glucose tolerance was caused by KRAS mutation and a novel clinical phenotype of Schimmelpenning syndrome. Our study indicated that clinical diagnosis of Schimmelpenning syndrome or related conditions should be reorganized with genetic diagnosis of postzygotic mutation. Moreover, further accumulation of genetically proven cases with mosaic RASopathies should be used to more accurately characterize phenotypic presentations of this syndrome and develop a future therapeutic strategy, such as molecular-targeted therapy.
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We obtained written informed consent from the patient’s parents in accordance with the ethic committee of the Institutional Review Board of Tokyo Medical and Dental University (article#: 2015-39) and in adherence to the principles of the Declaration of Helsinki.
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Nagatsuma, M., Takasawa, K., Yamauchi, T. et al. A postzygotic KRAS mutation in a patient with Schimmelpenning syndrome presenting with lipomatosis, renovascular hypertension, and diabetes mellitus. J Hum Genet 64, 177–181 (2019). https://doi.org/10.1038/s10038-018-0539-3
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DOI: https://doi.org/10.1038/s10038-018-0539-3
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