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Cardiofaciocutaneous syndrome 1(CFC1)

MedGen UID:
852267
Concept ID:
CN029449
Disease or Syndrome
Synonyms: BRAF-Related Cardiofaciocutaneous Syndrome; CFC1; Congenital heart defects characteristic facial appearance ectodermal abnormalities and growth failure
 
Gene (location): BRAF (7q34)
 
Monarch Initiative: MONDO:0007265
OMIM®: 115150

Disease characteristics

Excerpted from the GeneReview: Cardiofaciocutaneous Syndrome
Cardiofaciocutaneous (CFC) syndrome is characterized by cardiac abnormalities (pulmonic stenosis and other valve dysplasias, septal defects, hypertrophic cardiomyopathy, rhythm disturbances), distinctive craniofacial appearance, and cutaneous abnormalities (including xerosis, hyperkeratosis, ichthyosis, keratosis pilaris, ulerythema ophryogenes, eczema, pigmented moles, hemangiomas, and palmoplantar hyperkeratosis). The hair is typically sparse, curly, fine or thick, and woolly or brittle; eyelashes and eyebrows may be absent or sparse. Nails may be dystrophic or fast growing. Affected individuals typically have some form of neurologic and/or cognitive delay (ranging from mild to severe). Most individuals have severe feeding issues, which can contribute to poor growth, and many require nasogastric or gastrostomy tube feeding. Many affected individuals have eye findings, including strabismus, nystagmus, refractive errors, and optic nerve hypoplasia. Seizures may be present and can be refractory to therapy. [from GeneReviews]
Authors:
Katherine A Rauen   view full author information

Additional description

From OMIM
Cardiofaciocutaneous (CFC) syndrome is a multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects, and mental retardation (summary by Niihori et al., 2006). The heart defects include pulmonic stenosis, atrial septal defect, and hypertrophic cardiomyopathy. Some patients have ectodermal abnormalities such as sparse and friable hair, hyperkeratotic skin lesions, and a generalized ichthyosis-like condition. Typical facial characteristics include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. Most cases occur sporadically, but autosomal dominant transmission has been rarely reported (Linden and Price, 2011). Roberts et al. (2006) provided a detailed review of CFC syndrome, including a discussion of the phenotypic overlap of CFC syndrome with Noonan syndrome (NS1; 163950) and Costello syndrome (218040). Genetic Heterogeneity of Cardiofaciocutaneous Syndrome Other forms of cardiofaciocutaneous syndrome include CFC2 (615278), caused by mutation in the KRAS gene (190070); CFC3 (615279), caused by mutation in the MAP2K1 gene (176872); and CFC4 (615280), caused by mutation in the MAP2K2 gene (601263). The protein products of these causative genes, including BRAF, interact in a common RAS/ERK (see 601795) pathway that regulates cell differentiation, proliferation, and apoptosis (summary by Roberts et al., 2006).  http://www.omim.org/entry/115150

Professional guidelines

PubMed

Serbinski CR, Vanderwal A, Chadwell SE, Sanchez AI, Hopkin RJ, Hufnagel RB, Weaver KN, Prada CE
Am J Med Genet A 2024 Feb;194(2):195-202. Epub 2023 Sep 29 doi: 10.1002/ajmg.a.63397. PMID: 37774117
Yi JS, Perla S, Bennett AM
Cardiovasc Drugs Ther 2023 Dec;37(6):1193-1204. Epub 2022 Feb 14 doi: 10.1007/s10557-022-07324-0. PMID: 35156148
Kenney-Jung DL, Rogers DJ, Kroening SJ, Zatkalik AL, Whitmarsh AE, Roberts AE, Zenker M, Gambardella ML, Contaldo I, Leoni C, Onesimo R, Zampino G, Tartaglia M, Battaglia DI, Pierpont EI
Am J Med Genet C Semin Med Genet 2022 Dec;190(4):501-509. Epub 2022 Nov 29 doi: 10.1002/ajmg.c.32022. PMID: 36448195Free PMC Article

Recent clinical studies

Etiology

Handa A, Tsujioka Y, Nishimura G, Nozaki T, Kono T, Jinzaki M, Harms T, Connolly SA, Sato TS, Sato Y
Radiographics 2024 May;44(5):e230153. doi: 10.1148/rg.230153. PMID: 38602868
Stevenson DA, Viscogliosi G, Leoni C
Am J Med Genet C Semin Med Genet 2022 Dec;190(4):459-470. Epub 2022 Dec 2 doi: 10.1002/ajmg.c.32020. PMID: 36461161
Hebron KE, Hernandez ER, Yohe ME
Dis Model Mech 2022 Feb 1;15(2) Epub 2022 Feb 18 doi: 10.1242/dmm.049107. PMID: 35178568Free PMC Article
Cao H, Alrejaye N, Klein OD, Goodwin AF, Oberoi S
Orthod Craniofac Res 2017 Jun;20 Suppl 1(Suppl 1):32-38. doi: 10.1111/ocr.12144. PMID: 28643916Free PMC Article
Smpokou P, Zand DJ, Rosenbaum KN, Summar ML
Clin Genet 2015 Dec;88(6):516-22. Epub 2015 Mar 4 doi: 10.1111/cge.12568. PMID: 25683281

Diagnosis

Scorrano G, David E, Calì E, Chimenz R, La Bella S, Di Ludovico A, Di Rosa G, Gitto E, Mankad K, Nardello R, Mangano GD, Leoni C, Ceravolo G
Genes (Basel) 2023 Nov 22;14(12) doi: 10.3390/genes14122111. PMID: 38136934Free PMC Article
Cao H, Alrejaye N, Klein OD, Goodwin AF, Oberoi S
Orthod Craniofac Res 2017 Jun;20 Suppl 1(Suppl 1):32-38. doi: 10.1111/ocr.12144. PMID: 28643916Free PMC Article
Johnson B, Goldberg-Strassler D, Gripp K, Thacker M, Leoni C, Stevenson D
Am J Med Genet A 2015 Jan;167A(1):40-4. Epub 2014 Oct 24 doi: 10.1002/ajmg.a.36828. PMID: 25346259
Tartaglia M, Gelb BD, Zenker M
Best Pract Res Clin Endocrinol Metab 2011 Feb;25(1):161-79. doi: 10.1016/j.beem.2010.09.002. PMID: 21396583Free PMC Article
Kavamura MI, Peres CA, Alchorne MM, Brunoni D
Am J Med Genet 2002 Sep 15;112(1):12-6. doi: 10.1002/ajmg.10681. PMID: 12239713

Therapy

Kenney-Jung DL, Rogers DJ, Kroening SJ, Zatkalik AL, Whitmarsh AE, Roberts AE, Zenker M, Gambardella ML, Contaldo I, Leoni C, Onesimo R, Zampino G, Tartaglia M, Battaglia DI, Pierpont EI
Am J Med Genet C Semin Med Genet 2022 Dec;190(4):501-509. Epub 2022 Nov 29 doi: 10.1002/ajmg.c.32022. PMID: 36448195Free PMC Article
Bessis D, Morice-Picard F, Bourrat E, Abadie C, Aouinti S, Baumann C, Best M, Bursztejn AC, Capri Y, Chiaverini C, Coubes C, Giuliano F, Hadj-Rabia S, Jacquemont ML, Lacombe D, Lyonnet S, Mallet S, Mazereeuw-Hautier J, Miquel J, Molinari N, Parfait B, Pernet C, Philip N, Pinson L, Pouvreau N, Vial Y, Sarda P, Sigaudy S, Verloes A, Cavé H, Geneviève D
Br J Dermatol 2019 Jan;180(1):172-180. Epub 2018 Sep 30 doi: 10.1111/bjd.17077. PMID: 30141192
Carruth BP, Wladis EJ
Orbit 2013 Feb;32(1):39-41. Epub 2012 Dec 28 doi: 10.3109/01676830.2012.736598. PMID: 23273045
Rauen KA, Banerjee A, Bishop WR, Lauchle JO, McCormick F, McMahon M, Melese T, Munster PN, Nadaf S, Packer RJ, Sebolt-Leopold J, Viskochil DH
Am J Med Genet C Semin Med Genet 2011 May 15;157C(2):136-46. Epub 2011 Apr 14 doi: 10.1002/ajmg.c.30294. PMID: 21495172Free PMC Article

Prognosis

Boleti O, Norrish G, Field E, Dady K, Summers K, Nepali G, Bhole V, Uzun O, Wong A, Daubeney PEF, Stuart G, Fernandes P, McLeod K, Ilina M, Ali MNL, Bharucha T, Donne GD, Brown E, Linter K, Jones CB, Searle J, Regan W, Mathur S, Boyd N, Reinhardt Z, Duignan S, Prendiville T, Adwani S, Kaski JP
ESC Heart Fail 2024 Apr;11(2):923-936. Epub 2024 Jan 13 doi: 10.1002/ehf2.14637. PMID: 38217456Free PMC Article
Scorrano G, David E, Calì E, Chimenz R, La Bella S, Di Ludovico A, Di Rosa G, Gitto E, Mankad K, Nardello R, Mangano GD, Leoni C, Ceravolo G
Genes (Basel) 2023 Nov 22;14(12) doi: 10.3390/genes14122111. PMID: 38136934Free PMC Article
Feng B, Li X, Zhang Q, Wang Y, Gu S, Yao RE, Li Z, Gao S, Chang G, Li Q, Li N, Fu L, Wang J, Wang X
Orphanet J Rare Dis 2023 Sep 11;18(1):284. doi: 10.1186/s13023-023-02878-0. PMID: 37697378Free PMC Article
Foy AMH, Hudock RL, Shanley R, Pierpont EI
J Neurodev Disord 2022 Jan 12;14(1):5. doi: 10.1186/s11689-021-09414-w. PMID: 35021989Free PMC Article
Abe Y, Aoki Y, Kuriyama S, Kawame H, Okamoto N, Kurosawa K, Ohashi H, Mizuno S, Ogata T, Kure S, Niihori T, Matsubara Y; Costello and CFC syndrome study group in Japan
Am J Med Genet A 2012 May;158A(5):1083-94. Epub 2012 Apr 11 doi: 10.1002/ajmg.a.35292. PMID: 22495831

Clinical prediction guides

Feng B, Li X, Zhang Q, Wang Y, Gu S, Yao RE, Li Z, Gao S, Chang G, Li Q, Li N, Fu L, Wang J, Wang X
Orphanet J Rare Dis 2023 Sep 11;18(1):284. doi: 10.1186/s13023-023-02878-0. PMID: 37697378Free PMC Article
Foy AMH, Hudock RL, Shanley R, Pierpont EI
J Neurodev Disord 2022 Jan 12;14(1):5. doi: 10.1186/s11689-021-09414-w. PMID: 35021989Free PMC Article
Jurcă MC, Iuhas OA, Puiu M, Chiriţă-Emandi A, Andreescu NI, Petcheşi CD, Jurcă AD, Magyar I, Jurcă SI, Kozma K, Severin EM, Bembea M
Rom J Morphol Embryol 2021 Apr-Jun;62(2):563-568. doi: 10.47162/RJME.62.2.23. PMID: 35024745Free PMC Article
Shionoya Y, Yamamoto M, Sunada K, Nakamura K
Anesth Prog 2020 Spring;67(1):45-47. doi: 10.2344/anpr-67-01-07. PMID: 32191511Free PMC Article
Johnson B, Goldberg-Strassler D, Gripp K, Thacker M, Leoni C, Stevenson D
Am J Med Genet A 2015 Jan;167A(1):40-4. Epub 2014 Oct 24 doi: 10.1002/ajmg.a.36828. PMID: 25346259

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