{
  "abstract": "Background and Clinical Significance: Cardiofaciocutaneous syndrome (CFC) is a rare autosomal dominant RASopathy characterized by craniofacial dysmorphism, congenital heart defects, cutaneous abnormalities, growth impairment, and neurodevelopmental delay. Pathogenic variants in KRAS account for a minority of cases and define cardiofaciocutaneous syndrome type 2 (CFC2). Establishing a molecular diagnosis is often challenging because of the substantial clinical overlap among RASopathies, including Noonan and Costello syndromes. Case Presentation: We describe a one-year-old boy presenting with macrocephaly, ventriculomegaly, hypotonia, developmental delay, hypertrophic cardiomyopathy, gastroesophageal reflux, and mild dermatological abnormalities. To clarify the diagnosis, a custom next-generation sequencing panel targeting RASopathy-associated genes was performed. Genetic analysis identified a heterozygous KRAS variant, NM_033360.4:c.101C>G, p.(Pro34Arg), which was confirmed by Sanger sequencing and shown to have arisen de novo through parental testing. Additional variants of uncertain significance were detected in ABCC9, CACNA1G, and DES; however, these were considered unlikely to account for the phenotype because of limited clinical concordance and current ACMG/AMP classification. The KRAS variant was classified as pathogenic based on its de novo occurrence, absence from population databases, localization within a critical functional domain, supportive computational evidence, and previously reported pathogenic substitutions affecting the same residue. Conclusions: This case provides additional evidence supporting the pathogenicity of KRAS p.(Pro34Arg), a variant reported only rarely in association with CFC. The observed phenotype further expands the clinical spectrum of KRAS-associated CFC and highlights the value of comprehensive molecular testing for the differential diagnosis of RASopathies and the refinement of genotype-phenotype correlations.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Genetic, Málaga Regional University Hospital, 29011 Málaga, Spain.",
    "Department of Biochemistry, Molecular Biology and Immunology, University of Málaga, 29071 Málaga, Spain.",
    "Gerona Institute of Biomedical Research (IDIBGI), 17190 Gerona, Spain.",
    "Clinical Genetics Department, GENinCode SLU (Affiliate of GENinCode UK), 08244 Barcelona, Spain.",
    "Department of Genetic, Gerona University Hospital Santa, Caterina, 17190 Gerona, Spain."
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Francisco J Mérida De Ia Torre",
      "orcid": "0000-0002-1545-3665"
    },
    {
      "affs": [
        2
      ],
      "name": "Mónica Coll Vidal"
    },
    {
      "affs": [
        3
      ],
      "name": "Ivette Rubio Martínez"
    },
    {
      "affs": [
        3
      ],
      "name": "Lucía Quintana Tello"
    },
    {
      "affs": [
        4
      ],
      "name": "Ramón Brugada Terradellas"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bkdcq1vj38pwj.bib",
  "cited_by": 0,
  "doi": "10.3390/reports9040335",
  "fulltext_url": "https://europepmc.org/articles/PMC13692532",
  "id": "bkdcq1vj38pwj",
  "issns": [
    "2571-841X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42924787",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Protein Tyrosine Phosphatases"
    ]
  ],
  "openalex": "W7213673066",
  "pdf_url": "https://europepmc.org/articles/PMC13692532?pdf=render",
  "pmcid": "PMC13692532",
  "pmid": "42924787",
  "published": "2026-10-05",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bkdcq1vj38pwj.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:36Z",
      "native_id": "MED:42924787",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42924787"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Protein Tyrosine Phosphatases",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Case Report A Rare Cause of Cardiofaciocutaneous Syndrome-KRAS p.Pro34arg: Clinical Delineation, Diagnostic Challenges, and Implications for RASopathy Classification.",
  "title_text": "Case Report A Rare Cause of Cardiofaciocutaneous Syndrome-KRAS p.Pro34arg: Clinical Delineation, Diagnostic Challenges, and Implications for RASopathy Classification.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:36Z",
  "url": "https://research.draconitic.com/paper/bkdcq1vj38pwj",
  "venue": "Reports (MDPI)",
  "versions": []
}