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Cited by 271Protein Tyrosine PhosphatasesGenomics and Rare DiseasesGenetic and rare skin diseases.

The cardiofaciocutaneous syndrome

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Roberts, A, Allanson, J, Jadico, S K, Kavamura, M I, Noonan, J, Opitz, J M, Young, T, Neri, G·2006·Journal of Medical Genetics
DOI 10.1136/jmg.2006.042796PMC PMC2563180
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Abstract

The cardiofaciocutaneous (CFC) syndrome is a condition of sporadic occurrence, with patients showing multiple congenital anomalies and mental retardation. It is characterised by failure to thrive, relative macrocephaly, a distinctive face with prominent forehead, bitemporal constriction, absence of eyebrows, hypertelorism, downward-slanting palpebral fissures often with epicanthic folds, depressed nasal root and a bulbous tip of the nose. The cutaneous involvement consists of dry, hyperkeratotic, scaly skin, sparse and curly hair, and cavernous haemangiomata. Most patients have a congenital heart defect, most commonly pulmonic stenosis and hypertrophic cardiomyopathy. The developmental delay usually is moderate to severe. The syndrome is caused by gain-of-function mutations in four different genes BRAF, KRAS, mitogen-activated protein/extracellular signal-regulated kinase MEK1 and MEK2, all belonging to the same RAS-extracellular signal-regulated kinase (ERK) pathway that regulates cell differentiation, proliferation and apoptosis. The CFC syndrome is a member of a family of syndromes that includes the Noonan and Costello syndromes, presenting with phenotypic similarities. Noonan syndrome is caused by mutations in the protein tyrosine phosphatase SHP-2 gene (PTPN11), with a few people having a mutation in KRAS. Costello syndrome is caused by mutations in HRAS. The protein products of these genes also belong to the RAS-ERK pathway. Thus, the clinical overlap of these three conditions, which often poses a problem of differential diagnosis, is explained by their pathogenetic relatedness.

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  • The cardiofaciocutaneous syndrome (CFC, OMIM 115150) is caused by gain-of-function mutations in four different genes: BRAF (7q34), KRAS2 (12p12.1), MEK1 (15q21), and MEK2 (7q32).

    “The cardiofaciocutaneous syndrome (CFC, OMIM 115150) is caused by gain-of function mutations in 4 different genes BRAF (7q34), KRAS2 (12p12.1),MEK1 (15q21), and MEK2 (7q32), all belonging to the same RAS-extracellular signal-regulated kinase (ERK) pathway that regulates cell differentiation, proliferation, and apoptosis [Roberts et al., 2006].”

    From Ectodermal dysplasias: Clinical and molecular review (2009) · cites this paper as Roberts et al., 2006

    The Abstract (page unavailable) states that CFC is caused by gain-of-function mutations in BRAF, KRAS, MEK1 and MEK2, and places them in the RAS–ERK pathway. The cited copy does not provide the chromosome-band locations in the claim or use the name KRAS2, so those details are not verified by this source. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • The RAS-extracellular signal-regulated kinase (ERK) pathway regulates cell differentiation, proliferation, and apoptosis.

    “The cardiofaciocutaneous syndrome (CFC, OMIM 115150) is caused by gain-of function mutations in 4 different genes BRAF (7q34), KRAS2 (12p12.1),MEK1 (15q21), and MEK2 (7q32), all belonging to the same RAS-extracellular signal-regulated kinase (ERK) pathway that regulates cell differentiation, proliferation, and apoptosis [Roberts et al., 2006].”

    From Ectodermal dysplasias: Clinical and molecular review (2009) · cites this paper as Roberts et al., 2006

  • The four genes causing cardiofaciocutaneous syndrome (BRAF, KRAS2, MEK1, MEK2) all belong to the same RAS-extracellular signal-regulated kinase (ERK) pathway.

    “The cardiofaciocutaneous syndrome (CFC, OMIM 115150) is caused by gain-of function mutations in 4 different genes BRAF (7q34), KRAS2 (12p12.1),MEK1 (15q21), and MEK2 (7q32), all belonging to the same RAS-extracellular signal-regulated kinase (ERK) pathway that regulates cell differentiation, proliferation, and apoptosis [Roberts et al., 2006].”

    From Ectodermal dysplasias: Clinical and molecular review (2009) · cites this paper as Roberts et al., 2006

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Research works printed but not linked: 65

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Authors
Roberts, A., Allanson, J., Jadico, S. K., Kavamura, M. I., Noonan, J., Opitz, J. M., Young, T., & Neri, G.
Affiliations
  • Harvard University (US)
  • University of Ottawa (CA)
  • University of Pennsylvania (US)
  • Universidade Federal de São Paulo (BR)
  • University of Kentucky (US)
  • University of Utah (US)
  • Duke University (US)
  • Università Cattolica del Sacro Cuore (IT)
Corresponding author
Neri, G
ORCID
Venue
Journal of Medical Genetics
Publisher
BMJ
Published
2006-07-06
Volume
43
Issue
11
Pages
833-842
ISSN
  • 0022-2593 (ISSN-L)
  • 1468-6244
DOI
10.1136/jmg.2006.042796
PMC
PMC2563180
OpenAlex
W2143963530
Cited by
271
References
1
Citations by year
2026: 5 · 2025: 6 · 2024: 10 · 2023: 7 · 2022: 14 · 2021: 7 · 2020: 11 · 2019: 12 · 2018: 6 · 2017: 16 · 2016: 15 · 2015: 14 · 2014: 18 · 2013: 14 · 2012: 17
FWCI
1.70
Type
journal article
Language
en
Open access
Locations
  • Journal of Medical Genetics (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and rare skin diseases.
Keywords
cardiofaciocutaneous syndrome, Noonan syndrome, Costello syndrome, Ras/ERK pathway, BRAF mutation, KRAS mutation, PTPN11, HRAS, congenital heart disease, hypertrophic cardiomyopathy, pulmonary stenosis, developmental delay, congenital malformations, differential diagnosis
MeSH terms
Abnormalities, Multiple, Diagnosis, Differential, Digestive System Abnormalities, Eye Abnormalities, Female, Genes, Heart Defects, Congenital, Hematologic Diseases, Humans, Male, Mutation, Nervous System Malformations, Noonan Syndrome, Skin Abnormalities, Syndrome, Facies

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