Write a PREreview

Background: Cardiofaciocutaneous syndrome (CFC) is a rare RASopathy characterized by craniofacial dysmorphism, cutaneous abnormalities, congenital heart disease, and neurodevelopmental impairment. Clinical overlap with Noonan and Costello syndromes often complicates diagnosis, making molecular confirmation essential. Case Presentation: We report a one-year-old boy presenting with progressive macrocephaly, axial hypotonia, gastroesophageal reflux, dermatologic abnormalities, and hypertrophic cardiomyopathy. Brain magnetic resonance imaging revealed supratentorial ventriculomegaly, aqueductal enlargement, and periventricular gliosis, consistent with evolving hydrocephalus. Echocardiography demonstrated concentric left ventricular hypertrophy with preserved systolic function. Targeted next-generation sequencing identified a heterozygous de novo KRAS c.101C>G (p.Pro34Arg) variant. This pathogenic variant has been reported only once previously in association with CFC. Other substitutions affecting the same residue further support the functional importance of codon 34 in KRAS. Discussion: The patient’s phenotype, including prominent neurological involvement and early-onset cardiac hypertrophy, is highly consistent with KRAS-related CFC. Differentia tion from other RASopathies is clinically challenging because of overlapping manifestations; however, the absence of characteristic features of Costello syndrome and the severity of neurological findings favored CFC. Conclusions: This case provides additional evidence supporting the pathogenicity of the KRAS p.Pro34Arg variant and expands the phenotypic spectrum of KRAS-associated CFC. Our findings emphasize the importance of integrating detailed clinical evaluation with molecular testing in infants presenting with complex neurocardiac manifestations suggestive of a RASopathy.