CFC4
MCID: CRD167
MIFTS: 35

Cardiofaciocutaneous Syndrome 4 (CFC4)

Categories: Cardiovascular diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Cardiofaciocutaneous Syndrome 4

MalaCards integrated aliases for Cardiofaciocutaneous Syndrome 4:

Name: Cardiofaciocutaneous Syndrome 4 56 12 73 29 6 15 71
Cfc4 56 12 73
Cardiofaciocutaneous Syndrome, Type 4 39

Characteristics:

OMIM:

56
Inheritance:
autosomal dominant


Classifications:



Summaries for Cardiofaciocutaneous Syndrome 4

UniProtKB/Swiss-Prot : 73 Cardiofaciocutaneous syndrome 4: A form of cardiofaciocutaneous syndrome, a multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices.

MalaCards based summary : Cardiofaciocutaneous Syndrome 4, also known as cfc4, is related to pulmonary valve disease and pulmonary valve stenosis. An important gene associated with Cardiofaciocutaneous Syndrome 4 is MAP2K2 (Mitogen-Activated Protein Kinase Kinase 2). Affiliated tissues include skin and heart, and related phenotypes are global developmental delay and muscular hypotonia

Disease Ontology : 12 A cardiofaciocutaneous syndrome that has material basis in heterozygous mutation in MAPK2K2 on chromosome 19p13.3.

OMIM : 56 Cardiofaciocutaneous (CFC) syndrome is a multiple congenital anomaly disorder in which individuals have characteristic craniofacial features, cardiac defects, ectodermal anomalies, gastrointestinal dysfunction, and neurocognitive delay (summary by Rauen et al., 2010). (615280)

Related Diseases for Cardiofaciocutaneous Syndrome 4

Diseases in the Cardiofaciocutaneous Syndrome 1 family:

Cardiofaciocutaneous Syndrome 2 Cardiofaciocutaneous Syndrome 3
Cardiofaciocutaneous Syndrome 4

Diseases related to Cardiofaciocutaneous Syndrome 4 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 pulmonary valve disease 10.1 MAP2K2 CFC1
2 pulmonary valve stenosis 10.0 MAP2K2 CFC1
3 cardiofaciocutaneous syndrome 1 9.7 MAP2K2 CFC1
4 facioscapulohumeral muscular dystrophy 2 9.7 MBD3L5 MBD3L4
5 colorectal cancer, hereditary nonpolyposis, type 2 9.7 AGBL5 AGBL4
6 lynch syndrome i 9.5 AGBL5 AGBL4
7 cardiofaciocutaneous syndrome 3 9.0 CFC1 CCPG1 AGBL5 AGBL4
8 cardiofaciocutaneous syndrome 2 9.0 CFC1 CCPG1 AGBL5 AGBL4

Graphical network of the top 20 diseases related to Cardiofaciocutaneous Syndrome 4:



Diseases related to Cardiofaciocutaneous Syndrome 4

Symptoms & Phenotypes for Cardiofaciocutaneous Syndrome 4

Human phenotypes related to Cardiofaciocutaneous Syndrome 4:

31 (show all 24)
# Description HPO Frequency HPO Source Accession
1 global developmental delay 31 HP:0001263
2 muscular hypotonia 31 HP:0001252
3 scoliosis 31 HP:0002650
4 short stature 31 HP:0004322
5 hyperhidrosis 31 HP:0000975
6 nystagmus 31 HP:0000639
7 strabismus 31 HP:0000486
8 abnormal aortic valve morphology 31 HP:0001646
9 myopia 31 HP:0000545
10 telecanthus 31 HP:0000506
11 high forehead 31 HP:0000348
12 pulmonic stenosis 31 HP:0001642
13 hyperextensible skin 31 HP:0000974
14 multiple lentigines 31 HP:0001003
15 cerebellar hypoplasia 31 HP:0001321
16 abnormality of the sternum 31 HP:0000766
17 hypoplasia of the corpus callosum 31 HP:0002079
18 absent eyebrow 31 HP:0002223
19 optic nerve hypoplasia 31 HP:0000609
20 developmental cataract 31 HP:0000519
21 narrow forehead 31 HP:0000341
22 heat intolerance 31 HP:0002046
23 abnormality of lateral ventricle 31 HP:0030047
24 abnormal ventricular septum morphology 31 HP:0010438

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Nose:
depressed nasal bridge
short nose

Growth Other:
failure to thrive

Head And Neck Eyes:
nystagmus
strabismus
ptosis
myopia
telecanthus
more
Prenatal Manifestations Amniotic Fluid:
polyhydramnios

Skin Nails Hair Skin:
multiple lentigines
palmoplantar hyperkeratosis
hyperkeratosis pilaris
nevi
hemangiomas

Muscle Soft Tissue:
hypotonia

Head And Neck Head:
macrocephaly, relative

Genitourinary External Genitalia Male:
penoscrotal inversion

Growth Height:
short stature

Head And Neck Face:
prominent forehead
long, narrow face
bitemporal narrowing
prominent supraorbital fissures

Head And Neck Ears:
low-set ears
posteriorly rotated ears

Cardiovascular Heart:
pulmonic stenosis

Skin Nails Hair Hair:
sparse hair
sparse eyelashes
curly hair
sparse eyebrows

Neurologic Central Nervous System:
developmental delay

Chest Ribs Sternum Clavicles And Scapulae:
pectus deformity

Clinical features from OMIM:

615280

Drugs & Therapeutics for Cardiofaciocutaneous Syndrome 4

Search Clinical Trials , NIH Clinical Center for Cardiofaciocutaneous Syndrome 4

Genetic Tests for Cardiofaciocutaneous Syndrome 4

Genetic tests related to Cardiofaciocutaneous Syndrome 4:

# Genetic test Affiliating Genes
1 Cardiofaciocutaneous Syndrome 4 29 MAP2K2

Anatomical Context for Cardiofaciocutaneous Syndrome 4

MalaCards organs/tissues related to Cardiofaciocutaneous Syndrome 4:

40
Skin, Heart

Publications for Cardiofaciocutaneous Syndrome 4

Articles related to Cardiofaciocutaneous Syndrome 4:

# Title Authors PMID Year
1
Cardiofaciocutaneous syndrome in a mother and two sons with a MEK2 mutation. 6 56
21178588 2011
2
Molecular and functional analysis of a novel MEK2 mutation in cardio-facio-cutaneous syndrome: transmission through four generations. 6 56
20358587 2010
3
Mutation and phenotypic spectrum in patients with cardio-facio-cutaneous and Costello syndrome. 56 6
18042262 2008
4
Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome. 6 56
16439621 2006
5
Germline mutations of MEK in cardio-facio-cutaneous syndrome are sensitive to MEK and RAF inhibition: implications for therapeutic options. 6
17981815 2008
6
Cardiofaciocutaneous Syndrome 6
20301365 2007

Variations for Cardiofaciocutaneous Syndrome 4

ClinVar genetic disease variations for Cardiofaciocutaneous Syndrome 4:

6 (show all 19) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 MAP2K2 NM_030662.3(MAP2K2):c.383C>A (p.Pro128Gln)SNV Pathogenic 8275 rs267607230 19:4110574-4110574 19:4110576-4110576
2 MAP2K2 NM_030662.3(MAP2K2):c.170T>G (p.Phe57Cys)SNV Pathogenic 8272 rs121434497 19:4117550-4117550 19:4117552-4117552
3 MAP2K2 NM_030662.3(MAP2K2):c.169T>G (p.Phe57Val)SNV Pathogenic 8273 rs121434498 19:4117551-4117551 19:4117553-4117553
4 MAP2K2 NM_030662.3(MAP2K2):c.376A>G (p.Asn126Asp)SNV Pathogenic 376176 rs1057519806 19:4110581-4110581 19:4110583-4110583
5 MAP2K2 NM_030662.3(MAP2K2):c.191T>G (p.Val64Gly)SNV Likely pathogenic 431174 rs1135401787 19:4117529-4117529 19:4117531-4117531
6 MAP2K2 NM_030662.4(MAP2K2):c.400T>C (p.Tyr134His)SNV Likely pathogenic 8274 rs121434499 19:4110557-4110557 19:4110559-4110559
7 MAP2K2 NM_030662.3(MAP2K2):c.395G>A (p.Gly132Asp)SNV Likely pathogenic 30170 rs387906800 19:4110562-4110562 19:4110564-4110564
8 MAP2K2 NM_030662.3(MAP2K2):c.937C>T (p.Arg313Trp)SNV Uncertain significance 280685 rs772831628 19:4097324-4097324 19:4097326-4097326
9 MAP2K2 NM_030662.4(MAP2K2):c.1187C>T (p.Thr396Met)SNV Uncertain significance 279960 rs117945277 19:4090612-4090612 19:4090614-4090614
10 MAP2K2 NM_030662.3(MAP2K2):c.890G>A (p.Arg297Gln)SNV Uncertain significance 285121 rs140111079 19:4099228-4099228 19:4099230-4099230
11 MAP2K2 NM_030662.3(MAP2K2):c.818A>G (p.Lys273Arg)SNV Likely benign 40824 rs539555837 19:4099300-4099300 19:4099302-4099302
12 MAP2K2 NM_030662.4(MAP2K2):c.846C>T (p.Pro282=)SNV Benign 40827 rs11539506 19:4099272-4099272 19:4099274-4099274
13 MAP2K2 NM_030662.4(MAP2K2):c.919+12A>GSNV Benign 40835 rs350911 19:4099187-4099187 19:4099189-4099189
14 MAP2K2 NM_030662.4(MAP2K2):c.453C>T (p.Asp151=)SNV Benign 46237 rs17851657 19:4102449-4102449 19:4102451-4102451
15 MAP2K2 NM_030662.4(MAP2K2):c.192C>T (p.Val64=)SNV Benign 40770 rs8157 19:4117528-4117528 19:4117530-4117530
16 MAP2K2 NM_030662.3(MAP2K2):c.303+18G>ASNV Benign 40789 rs116988721 19:4117399-4117399 19:4117401-4117401
17 MAP2K2 NM_030662.4(MAP2K2):c.405G>C (p.Gly135=)SNV Benign 40793 rs10424722 19:4110552-4110552 19:4110554-4110554
18 MAP2K2 NM_030662.4(MAP2K2):c.580+6G>ASNV Benign 40808 rs201435249 19:4101221-4101221 19:4101223-4101223
19 MAP2K2 NM_030662.4(MAP2K2):c.660C>A (p.Ile220=)SNV Benign 40816 rs10250 19:4101062-4101062 19:4101064-4101064

UniProtKB/Swiss-Prot genetic disease variations for Cardiofaciocutaneous Syndrome 4:

73
# Symbol AA change Variation ID SNP ID
1 MAP2K2 p.Phe57Cys VAR_035095 rs121434497
2 MAP2K2 p.Phe57Val VAR_069781 rs121434498
3 MAP2K2 p.Pro128Gln VAR_069782 rs267607230
4 MAP2K2 p.Tyr134His VAR_069783 rs121434499

Expression for Cardiofaciocutaneous Syndrome 4

Search GEO for disease gene expression data for Cardiofaciocutaneous Syndrome 4.

Pathways for Cardiofaciocutaneous Syndrome 4

GO Terms for Cardiofaciocutaneous Syndrome 4

Biological processes related to Cardiofaciocutaneous Syndrome 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein deglutamylation GO:0035608 8.96 AGBL5 AGBL4
2 methylation-dependent chromatin silencing GO:0006346 8.8 MBD3L5 MBD3L4 MBD3L3

Molecular functions related to Cardiofaciocutaneous Syndrome 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 tubulin binding GO:0015631 9.26 AGBL5 AGBL4
2 carboxypeptidase activity GO:0004180 9.16 AGBL5 AGBL4
3 metallocarboxypeptidase activity GO:0004181 8.96 AGBL5 AGBL4
4 methyl-CpG binding GO:0008327 8.8 MBD3L5 MBD3L4 MBD3L3

Sources for Cardiofaciocutaneous Syndrome 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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