Co-occurrence of Noonan and Cardiofaciocutaneous Syndrome Features in a Patient with KRAS Variant

Abstract

We report the case of a 3-year-old girl, who is the third child of nonconsanguineous parents with short stature, hypertrophic cardiomyopathy and mild dysmorphic features; all suggestive of Noonan syndrome. In addition, the patient presents with feeding difficulties, deep palmar and plantar creases, sparse hair, and delayed psychomotor and language development, all characteristics frequently observed in Cardio-facio-cutaneous syndrome. Molecular analysis of the Ras/MAPK pathway genes using high resolution melting curve analysis and gene sequencing revealed a de novo KRAS amino acid substitution of leucine to tryptophan at codon 53 (p.L53W). This substitution was recently described in an Iranian patient with Noonan syndrome. The findings described in the present report expand the phenotypic heterogeneity observed in RASopathy patients harbouring a KRAS substitution, and advocate for the inclusion of genes with low mutational frequency in genetic screening protocols for Noonan syndrome and other RASophaties.

A rare report of cardiofaciocutaneous syndrome and ulerythema ophryogenes

“…However, substantial mental disorders and cutaneous ectodermal abnormalities like ulerythema ophryogenes (seen in our case) suggest CFC syndrome (8). Other differential diagnoses that CFC syndrome can be mistaken with include Noonan syndrome, Costello syndrome, Leopard syndrome, Noonan-like syndrome with loose anagen hair, and Turner syndrome (7).…”

“…RASopathies are caused by germline mutations in genes encoding the RAS/MAPK signaling pathway and share overlapping clinical features. It is difficult to make a diagnosis based solely on the physical examination (7); therefore, a molecular genetics study is necessary for a definitive diagnosis.…”