Published Date: July 8, 2022

Full Text Article

Fibrous dysplasia in cardio-facio-cutaneous syndrome: A case report and review of literature

Authors: Xiaoao Dong, Nicholas C Y Png, Marielle V Fortier, Jiin Ying Lim, Kenneth P L Wong, Jonathan T L Choo, Ene Choo Tan, Saumya Shekhar Jamuar

Am J Med Genet A. 2022 Sep;188(9):2732-2737. doi: 10.1002/ajmg.a.62879. Epub 2022 Jul 7.


Cardio-facio-cutaneous (CFC) syndrome (OMIM #:115150, 615278, 615279, 615280) is a rare genetic condition caused by variants in the RAS/mitogen-activated protein kinase (MAPK) signal transduction pathway. Up to 75% of cases are caused by mutations in the BRAF gene, whereas KRAS gene mutation has only been reported in <2% of cases. CFC syndrome is characterized by cardiac abnormalities, distinctive craniofacial dysmorphism, and various cutaneous abnormalities. Musculoskeletal and orthopedic manifestations are also prevalent in patients with CFC syndrome, among which the most common are skeletal deformities and joint laxities. Dysplastic bone disorders, on the other hand, have not been reported in CFC syndrome before. We report on a case of symmetrical polyostotic fibrous dysplasia (FD) in a patient with CFC syndrome with the KRAS(NM_004985.5):c.57G>C; p.Leu19Phe variant. The FDs were incidentally picked up, and patient was conservatively managed and remained asymptomatic on follow-up. The same variant was reported previously in a patient with Oculoectodermal Syndrome (OES), who developed polyostotic non-ossifying fibroma (NOF). This case explores FD as a possible new clinical feature of CFC syndrome, and when linked to the historical case of OES, explores whether the KRAS(NM_004985.5):c.57G>C; p.Leu19Phe mutation may potentially contribute to the development of dysplastic bone lesions in patients with this particular mutation.

PMID: 35801299DOI: 10.1002/ajmg.a.62879