PedAM

Pediatric Disease Annotations & Medicines


	cardiofaciocutaneous syndrome

Disease ID	301
Disease	cardiofaciocutaneous syndrome
Definition	A rare genetic syndrome most often caused by BRAF gene mutations. It is characterized by a distinctive facial appearance (high forehead, short nose, and widely spaced eyes), sparse and brittle hair, skin disorders, heart malformations, mental retardation and developmental delay.
Synonym	cardio-facio-cutaneous syndrome cardio-facio-cutaneous syndrome (disorder) cardiofaciocutaneous (cfc) syndrome cardiofaciocutaneous syndrome 1 cfc cfc syndrome cfc1
Orphanet	ORPHANET:1340
OMIM	OMIM:115150 OMIM:602971 OMIM:605194
DOID	DOID:0060233
UMLS	C1275081
SNOMED-CT	SNOMEDCT_US_2016_09_01:403770008
Comorbidity	UMLS \| Disease \| Sentences' Count(Total Sentences:3) C0024305 \| non-hodgkin lymphoma \| 1 C0024299 \| lymphoma \| 1 C0019829 \| hodgkin lymphoma \| 1
Curated Gene	Entrez_id \| Symbol \| Resource(Total Genes:8) PTPN11 \| 5781 \| CTD_human HRAS \| 3265 \| CTD_human CFC1 \| 55997 \| OMIM BRAF \| 673 \| CLINVAR;CTD_human;UNIPROT;ORPHANET;GHR KRAS \| 3845 \| CTD_human;ORPHANET;GHR MAP2K1 \| 5604 \| CTD_human;ORPHANET;GHR MAP2K2 \| 5605 \| CLINVAR;CTD_human;ORPHANET;GHR TBCC \| 6903 \| OMIM
Inferring Gene	(Waiting for update.)
Text Mined Gene	Entrez_id \| Symbol \| Score \| Resource(Total Genes:31) 5911 \| RAP2A \| DISEASES 3845 \| KRAS \| DISEASES 284058 \| KANSL1 \| DISEASES 5605 \| MAP2K2 \| DISEASES 5595 \| MAPK3 \| DISEASES 23126 \| POGZ \| DISEASES 5921 \| RASA1 \| DISEASES 161742 \| SPRED1 \| DISEASES 5604 \| MAP2K1 \| DISEASES 9839 \| ZEB2 \| DISEASES 121391 \| KRT74 \| DISEASES 3265 \| HRAS \| DISEASES 27235 \| COQ2 \| DISEASES 5781 \| PTPN11 \| DISEASES 54345 \| SOX18 \| DISEASES 10252 \| SPRY1 \| DISEASES 26151 \| NAT9 \| DISEASES 4763 \| NF1 \| DISEASES 57107 \| PDSS2 \| DISEASES 8036 \| SHOC2 \| DISEASES 8242 \| KDM5C \| DISEASES 23590 \| PDSS1 \| DISEASES 3980 \| LIG3 \| DISEASES 54840 \| APTX \| DISEASES 2731 \| GLDC \| DISEASES 5609 \| MAP2K7 \| DISEASES 6654 \| SOS1 \| DISEASES 152789 \| JAKMIP1 \| DISEASES 8831 \| SYNGAP1 \| DISEASES 4043 \| LRPAP1 \| DISEASES 2110 \| ETFDH \| DISEASES
Locus	Symbol \| Locus(Total Locus:4) BRAF \| 7q34 MAP2K2 \| 19p13.3 MAP2K1 \| 15q22.31 KRAS \| 12p12.1

Disease ID	301
Disease	cardiofaciocutaneous syndrome
Integrated Phenotype	HPO \| Name(Total Integrated Phenotypes:79) HP:0000293 \| Full cheeks HP:0000499 \| Abnormality of the eyelashes HP:0007392 \| Excessive wrinkled skin HP:0000343 \| Long philtrum HP:0000470 \| Short neck HP:0011024 \| Abnormality of the gastrointestinal tract HP:0004422 \| Biparietal narrowing HP:0002217 \| Slow-growing hair HP:0001263 \| Global developmental delay HP:0000637 \| Long palpebral fissure HP:0200102 \| Sparse or absent eyelashes HP:0002353 \| EEG abnormality HP:0000286 \| Epicanthus HP:0001003 \| Multiple lentigines HP:0009891 \| Underdeveloped supraorbital ridges HP:0000126 \| Hydronephrosis HP:0008064 \| Ichthyosis HP:0100840 \| Aplasia/Hypoplasia of the eyebrow HP:0004322 \| Short stature HP:0000545 \| Myopia HP:0008391 \| Dystrophic fingernails HP:0000504 \| Abnormality of vision HP:0001631 \| Atrial septal defect HP:0003196 \| Short nose HP:0000767 \| Pectus excavatum HP:0001622 \| Premature birth HP:0000486 \| Strabismus HP:0001654 \| Abnormality of the heart valves HP:0000238 \| Hydrocephalus HP:0002997 \| Abnormality of the ulna HP:0000478 \| Abnormality of the eye HP:0000391 \| Thickened helices HP:0000280 \| Coarse facial features HP:0000508 \| Ptosis HP:0001252 \| Muscular hypotonia HP:0000962 \| Hyperkeratosis HP:0001260 \| Dysarthria HP:0002162 \| Low posterior hairline HP:0002299 \| Brittle hair HP:0002007 \| Frontal bossing HP:0000982 \| Palmoplantar keratoderma HP:0000316 \| Hypertelorism HP:0002967 \| Cubitus valgus HP:0001582 \| Redundant skin HP:0001639 \| Hypertrophic cardiomyopathy HP:0002213 \| Fine hair HP:0000256 \| Macrocephaly HP:0000028 \| Cryptorchidism HP:0000348 \| High forehead HP:0001531 \| Failure to thrive in infancy HP:0000176 \| Submucous cleft hard palate HP:0001642 \| Pulmonic stenosis HP:0000958 \| Dry skin HP:0001004 \| Lymphedema HP:0002167 \| Neurological speech impairment HP:0002564 \| Malformation of the heart and great vessels HP:0002857 \| Genu valgum HP:0007565 \| Multiple cafe-au-lait spots HP:0000400 \| Macrotia HP:0008070 \| Sparse hair HP:0010669 \| Cheekbone underdevelopment HP:0000368 \| Low-set, posteriorly rotated ears HP:0000974 \| Hyperextensible skin HP:0000639 \| Nystagmus HP:0000465 \| Webbed neck HP:0002650 \| Scoliosis HP:0001048 \| Cavernous hemangioma HP:0000494 \| Downslanted palpebral fissures HP:0008872 \| Feeding difficulties in infancy HP:0001249 \| Intellectual disability HP:0000648 \| Optic atrophy HP:0002120 \| Cerebral cortical atrophy HP:0000463 \| Anteverted nares HP:0006191 \| Deep palmar crease HP:0005280 \| Depressed nasal bridge HP:0012719 \| Functional abnormality of the gastrointestinal tract HP:0000218 \| High palate HP:0000276 \| Long face HP:0007440 \| Generalized hyperpigmentation
Text Mined Phenotype	HPO \| Name \| Sentences' Count(Total Phenotypes:3) HP:0012189 \| Hodgkin disease \| 1 HP:0002665 \| Lymphoma \| 1 HP:0012539 \| Non-Hodgkin lymphoma \| 1

Disease ID	301
Disease	cardiofaciocutaneous syndrome
Manually Symptom	UMLS \| Name(Total Manually Symptoms:2) C0031117 \| peripheral neuropathy C0023449 \| acute lymphoblastic leukaemia
Text Mined Symptom	(Waiting for update.)

Manually Genotype(Total Text Mining Genotypes:0)
(Waiting for update.)

All Snps(Total Genotypes:42)
snpId	pubmedId	geneId	geneSymbol	diseaseId	sourceId	sentence	score	Year	geneSymbol_dbSNP	CHROMOSOME	POS	REF	ALT
rs104894229	17324647	3265	HRAS	umls:C1275081	BeFree	We have observed unusual transverse distal phalangeal creases in two patients, one with Costello syndrome (G12S mutation in the HRAS gene) and one with cardio-facio-cutaneous (CFC) syndrome or possibly Noonan syndrome (Q22E mutation in the KRAS gene).	0.121085767	2007	HRAS;LRRC56	11	534289	C	T,G,A
rs104894360	16474405	3845	KRAS	umls:C1275081	BeFree	We discovered de novo germline KRAS mutations that introduce V14I, T58I or D153V amino acid substitutions in five individuals with Noonan syndrome and a P34R alteration in a individual with cardio-facio-cutaneous syndrome (MIM 115150), which has overlapping features with Noonan syndrome.	0.244071628	2006	KRAS	12	25209904	T	C,A
rs104894365	16474405	3845	KRAS	umls:C1275081	BeFree	We discovered de novo germline KRAS mutations that introduce V14I, T58I or D153V amino acid substitutions in five individuals with Noonan syndrome and a P34R alteration in a individual with cardio-facio-cutaneous syndrome (MIM 115150), which has overlapping features with Noonan syndrome.	0.244071628	2006	KRAS	12	25245345	C	T
rs104894366	16474405	3845	KRAS	umls:C1275081	BeFree	We discovered de novo germline KRAS mutations that introduce V14I, T58I or D153V amino acid substitutions in five individuals with Noonan syndrome and a P34R alteration in a individual with cardio-facio-cutaneous syndrome (MIM 115150), which has overlapping features with Noonan syndrome.	0.244071628	2006	KRAS	12	25245284	G	C,A
rs113488022	20735442	673	BRAF	umls:C1275081	BeFree	Germline mutation in BRAF codon 600 is compatible with human development: de novo p.V600G mutation identified in a patient with CFC syndrome.	0.567057489	2011	BRAF	7	140753336	A	T,G,C
rs121908595	17567882	5604	MAP2K1	umls:C1275081	BeFree	The patient died shortly thereafter and his post-mortem DNA analysis revealed a MEK1 mutation (Y130C) previously reported in CFC.	0.244071628	2007	MAP2K1	15	66436843	A	G
rs121913341	NA	673	BRAF	umls:C1275081	CLINVAR	NA	0.567057489	NA	BRAF	7	140753350	A	T,C
rs121913348	NA	673	BRAF	umls:C1275081	CLINVAR	NA	0.567057489	NA	BRAF	7	140781617	C	T,G,A
rs121913355	NA	673	BRAF	umls:C1275081	CLINVAR	NA	0.567057489	NA	BRAF	7	140781602	C	T,G,A
rs121913369	NA	673	BRAF	umls:C1275081	CLINVAR	NA	0.567057489	NA	BRAF	7	140753346	G	C,A
rs121913530	17324647	3265	HRAS	umls:C1275081	BeFree	We have observed unusual transverse distal phalangeal creases in two patients, one with Costello syndrome (G12S mutation in the HRAS gene) and one with cardio-facio-cutaneous (CFC) syndrome or possibly Noonan syndrome (Q22E mutation in the KRAS gene).	0.121085767	2007	KRAS	12	25245351	C	T,G,A
rs180177034	NA	673	BRAF	umls:C1275081	CLINVAR	NA	0.567057489	NA	BRAF	7	140801536	C	G
rs180177034	20523244	673	BRAF	umls:C1275081	BeFree	Sequencing analysis showed a germline p.A246P (c.736G>C) mutation in BRAF reported earlier in CFC syndrome.	0.567057489	2011	BRAF	7	140801536	C	G
rs180177035	NA	673	BRAF	umls:C1275081	CLINVAR	NA	0.567057489	NA	BRAF	7	140801502	T	C
rs180177036	NA	673	BRAF	umls:C1275081	CLINVAR	NA	0.567057489	NA	BRAF	7	140778053	C	G,A
rs180177037	NA	673	BRAF	umls:C1275081	CLINVAR	NA	0.567057489	NA	BRAF	7	140778013	T	C
rs180177037	18456719	673	BRAF	umls:C1275081	BeFree	In one patient with NS, we also identified a mutation, BRAF K499E, that has previously been reported in patients with CFC.	0.567057489	2008	BRAF	7	140778013	T	C
rs180177038	NA	673	BRAF	umls:C1275081	CLINVAR	NA	0.567057489	NA	BRAF	7	140778007	C	T,G
rs180177039	NA	673	BRAF	umls:C1275081	CLINVAR	NA	0.567057489	NA	BRAF	7	140778006	T	G,C,A
rs180177040	NA	673	BRAF	umls:C1275081	CLINVAR	NA	0.567057489	NA	BRAF	7	140754187	T	G,C
rs180177040	22876591	673	BRAF	umls:C1275081	BeFree	In this case report, we present a male CFCS patient with tight Achilles tendons with a de-novo heterozygote N581D mutation in the BRAF gene detected by DNA sequence analysis.	0.567057489	2012	BRAF	7	140754187	T	G,C
rs180177041	NA	673	BRAF	umls:C1275081	CLINVAR	NA	0.567057489	NA	BRAF	7	140777006	C	G
rs180177042	NA	673	BRAF	umls:C1275081	CLINVAR	NA	0.567057489	NA	BRAF	7	140749365	A	T,C
rs387906661	NA	673	BRAF	umls:C1275081	CLINVAR	NA	0.567057489	NA	BRAF	7	140801551	T	G
rs397507465	NA	673	BRAF	umls:C1275081	CLINVAR	NA	0.567057489	NA	BRAF	7	140801542	T	G
rs397507466	NA	673	BRAF	umls:C1275081	CLINVAR	NA	0.567057489	NA	BRAF	7	140801537	T	G,A
rs397507466	19416762	673	BRAF	umls:C1275081	BeFree	We speculate that the impact of p.L245F on BRAF protein function differs either qualitatively or quantitatively from those mutations associated with CFCS.	0.567057489	2009	BRAF	7	140801537	T	G,A
rs397507469	NA	673	BRAF	umls:C1275081	CLINVAR	NA	0.567057489	NA	BRAF	7	140801503	G	T
rs397507473	NA	673	BRAF	umls:C1275081	CLINVAR	NA	0.567057489	NA	BRAF	7	140781605	A	G
rs397507474	NA	673	BRAF	umls:C1275081	CLINVAR	NA	0.567057489	NA	BRAF	7	140778061	T	G
rs397507475	NA	673	BRAF	umls:C1275081	CLINVAR	NA	0.567057489	NA	BRAF	7	140778054	A	G
rs397507475	20395089	673	BRAF	umls:C1275081	BeFree	A girl with cardio-facio-cutaneous (CFC) syndrome due to a BRAF gene mutation (c.1454T→C, p.L485S) experienced repetitive epileptic spasms at the corrected age of 4 months.	0.567057489	2011	BRAF	7	140778054	A	G
rs397507480	NA	673	BRAF	umls:C1275081	CLINVAR	NA	0.567057489	NA	BRAF	7	140754233	A	C
rs397507483	NA	673	BRAF	umls:C1275081	CLINVAR	NA	0.567057489	NA	BRAF	7	140753348	C	A
rs397516892	NA	673	BRAF	umls:C1275081	CLINVAR	NA	0.567057489	NA	BRAF	7	140778066	G	T
rs397516893	NA	673	BRAF	umls:C1275081	CLINVAR	NA	0.567057489	NA	BRAF	7	140778048	A	C
rs397516894	NA	673	BRAF	umls:C1275081	CLINVAR	NA	0.567057489	NA	BRAF	7	140754208	G	A
rs397516895	NA	673	BRAF	umls:C1275081	CLINVAR	NA	0.567057489	NA	BRAF	7	140753392	A	T
rs397516904	NA	673	BRAF	umls:C1275081	CLINVAR	NA	0.567057489	NA	BRAF	7	140801487	T	G,C
rs397517147	18456719	6654	SOS1	umls:C1275081	BeFree	The SOS1 E433K mutation, identified in a patient diagnosed with CFC, has previously been reported in patients with NS.	0.001628651	2008	SOS1	2	39023131	C	T
rs730880517	NA	5605	MAP2K2	umls:C1275081	CLINVAR	NA	0.363257302	NA	MAP2K2	19	4117541	T	C
rs794729219	NA	673	BRAF	umls:C1275081	CLINVAR	NA	0.567057489	NA	BRAF	7	140753352	A	G

GWASdb Annotation(Total Genotypes:0)
(Waiting for update.)

GWASdb Snp Trait(Total Genotypes:0)
(Waiting for update.)

Mapped by lexical matching(Total Items:0)
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Mapped by homologous gene(Total Items:0)
(Waiting for update.)

Chemical(Total Drugs:0)
(Waiting for update.)

FDA approved drug and dosage information(Total Drugs:0)
(Waiting for update.)

FDA labeling changes(Total Drugs:0)
(Waiting for update.)