Am J Med Genet A. 2025 Nov 1:e64294. doi: 10.1002/ajmg.a.64294. Online ahead of print.
ABSTRACT
The Ras/mitogen-activated protein kinase (RAS/MAPK) pathway regulates cell proliferation, and dysregulation of this pathway has been linked to the increased risk of malignancy in a subset of disorders known as RASopathies (e.g., NF1, Costello syndrome, Noonan syndrome). However, reports of malignancy are rare in cardiofaciocutaneous (CFC) syndrome, which is caused by heterozygous pathogenic variants in BRAF, MAP2K1, MAP2K2, and KRAS. Somatic pathogenic variants in BRAF are one of the most common drivers of Langerhans cell histiocytosis (LCH), a neoplastic disorder that can present with lesions in a variety of locations. However, despite the association of somatic BRAF variants and LCH, individuals with CFC syndrome are not thought to have higher rates of LCH. Here, we report two individuals with CFC syndrome and LCH and review the literature examining this potential association.
PMID:41174928 | DOI:10.1002/ajmg.a.64294
