ArticleGenes, chromosomes & cancer2022
Successful treatment with MEK-inhibitor in a patient with NRAS-related cutaneous skeletal hypophosphatemia syndrome.
Article in Genes, chromosomes & cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Schimmelpenning-Feuerstein-Mims syndrome: a systematic review of clinical cases to identify genotype-phenotype associations.Frontiers in medicine · 2025Pooled it
- When X Does Not Mark the Spot: Autosomal Dominant and Recessive Forms of Renal Hypophosphatemic Rickets and Osteomalacia.Current osteoporosis reports · 2026Review
- Trametinib for multiple non-ossifying fibromas due to KRAS mosaic mutations: two case reports.Communications medicine · 2026Article
- Targeted treatment of hypophosphatemia with trametinib in HRAS-related mosaic RASopathy.Orphanet journal of rare diseases · 2025Article
- A Child with Cutaneous-Skeletal Hypophosphatemia Syndrome Caused by a Mosaic HRAS Mutation: Outcome of Treatment with Anti-FGF23 Antibody.Calcified tissue international · 2025Article
- Neurofibromatosis type I (NF1) and bone involvement in a pediatric setting: insights from FGF23 levels.Italian journal of pediatrics · 2025Observational
- Surgical management strategies and clinical outcomes of cutaneous skeletal hypophosphatemia syndrome: a case series.Frontiers in pediatrics · 2025Article
- Exploring New Drug Repurposing Opportunities for MEK Inhibitors in RASopathies: A Comprehensive Review of Safety, Efficacy, and Future Perspectives of Trametinib and Selumetinib.Life (Basel, Switzerland) · 2024Review
- Phosphaturic Mesenchymal Tumors with or without Phosphate Metabolism Derangements.Current oncology (Toronto, Ont.) · 2023Review
- Successful treatment with MEK-inhibitor in a patient with NRAS-related cutaneous skeletal hypophosphatemia syndrome.Genes, chromosomes & cancer · 2022Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cutaneous skeletal hypophosphatemia syndrome (CSHS) is caused by somatic mosaic NRAS variants and characterized by melanocytic/sebaceous naevi, eye, and brain malformations, and FGF23-mediated hypophosphatemic rickets. The MEK inhibitor Trametinib, acting on the RAS/MAPK pathway, is a candidate for CSHS therapy. A 4-year-old boy with seborrheic nevus, eye choristoma, multiple hamartomas, brain malformation, pleural lymphangioma and chylothorax developed severe hypophosphatemic rickets unresponsive to phosphate supplementation. The c.182A > G;p.(Gln61Arg) somatic NRAS variant found in DNA from nevus biopsy allowed diagnosing CSHS. We administered Trametinib for 15 months investigating the transcriptional effects at different time points by whole blood RNA-seq. Treatment resulted in prompt normalization of phosphatemia and phosphaturia, catch-up growth, chylothorax regression, improvement of bone mineral density, reduction of epidermal nevus and hamartomas. Global RNA sequencing on peripheral blood mononucleate cells showed transcriptional changes under MEK inhibition consisting in a strong sustained downregulation of signatures related to RAS/MAPK, PI3 kinase, WNT and YAP/TAZ pathways, reverting previously defined transcriptomic signatures. CSHS was effectively treated with a MEK inhibitor with almost complete recovery of rickets and partial regression of the phenotype. We identified "core" genes modulated by MEK inhibition potentially serving as surrogate markers of Trametinib action.
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