» Articles » PMID: 30443000

A Postzygotic KRAS Mutation in a Patient with Schimmelpenning Syndrome Presenting with Lipomatosis, Renovascular Hypertension, and Diabetes Mellitus

Overview
Journal J Hum Genet
Specialty Genetics
Date 2018 Nov 17
PMID 30443000
Citations 8
Authors
Affiliations
Soon will be listed here.
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.

Citing Articles

Cancer in Multilineage Mosaic RASopathies due to Pathogenic Variants in HRAS or KRAS: A Systematic Review and Meta-analysis.

Windrich J, Ney G, Rosenberg P, Kim J, Zenker M, Stewart D Clin Cancer Res. 2024; 30(22):5116-5121.

PMID: 39287844 PMC: 11565173. DOI: 10.1158/1078-0432.CCR-24-1928.


Exploring New Drug Repurposing Opportunities for MEK Inhibitors in RASopathies: A Comprehensive Review of Safety, Efficacy, and Future Perspectives of Trametinib and Selumetinib.

Gazzin A, Fornari F, Cardaropoli S, Carli D, Tartaglia M, Ferrero G Life (Basel). 2024; 14(6).

PMID: 38929714 PMC: 11204468. DOI: 10.3390/life14060731.


Classification of KRAS-Activating Mutations and the Implications for Therapeutic Intervention.

Johnson C, Burkhart D, Haigis K Cancer Discov. 2022; 12(4):913-923.

PMID: 35373279 PMC: 8988514. DOI: 10.1158/2159-8290.CD-22-0035.


Oral HRAS Mutation in Orofacial Nevus Sebaceous Syndrome (Schimmelpenning-Feuerstein-Mims-Syndrome): A Case Report With a Literature Survey.

Friedrich R, Gosau M, Luebke A, Hagel C, Kohlrusch F, Hahn M In Vivo. 2022; 36(1):274-293.

PMID: 34972725 PMC: 8765160. DOI: 10.21873/invivo.12701.


Identification of a recurrent mosaic variant in brain tissue from an individual with nevus sebaceous syndrome.

Green T, MacGregor D, Carden S, Harris R, Hewitt C, Berkovic S Cold Spring Harb Mol Case Stud. 2021; 7(6).

PMID: 34649968 PMC: 8751419. DOI: 10.1101/mcs.a006133.


References
1.
Booth T, Rollins N . MR imaging of the spine in epidermal nevus syndrome. AJNR Am J Neuroradiol. 2002; 23(9):1607-10. PMC: 7976813. View

2.
Alsohim F, Abou-Jaoude P, Ninet J, Pracros J, Phan A, Cochat P . Bilateral renal artery stenosis and epidermal nevus syndrome in a child. Pediatr Nephrol. 2011; 26(11):2081-4. PMC: 3178020. DOI: 10.1007/s00467-011-1949-z. View

3.
Mor A, Aizman E, George J, Kloog Y . Ras inhibition induces insulin sensitivity and glucose uptake. PLoS One. 2011; 6(6):e21712. PMC: 3126849. DOI: 10.1371/journal.pone.0021712. View

4.
Kurek K, Luks V, Ayturk U, Alomari A, Fishman S, Spencer S . Somatic mosaic activating mutations in PIK3CA cause CLOVES syndrome. Am J Hum Genet. 2012; 90(6):1108-15. PMC: 3370283. DOI: 10.1016/j.ajhg.2012.05.006. View

5.
Groesser L, Herschberger E, Ruetten A, Ruivenkamp C, Lopriore E, Zutt M . Postzygotic HRAS and KRAS mutations cause nevus sebaceous and Schimmelpenning syndrome. Nat Genet. 2012; 44(7):783-7. DOI: 10.1038/ng.2316. View