MCID: ORF002
MIFTS: 44

Orofacial Cleft

Categories: Fetal diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Orofacial Cleft

MalaCards integrated aliases for Orofacial Cleft:

Name: Orofacial Cleft 12 29 6 15
Cleft, Orofacial 39

Classifications:



External Ids:

Disease Ontology 12 DOID:0050567

Summaries for Orofacial Cleft

Disease Ontology : 12 A physical disorder that is characterized by cleft lip and/or cleft palate that result in feeding, speech and hearing problems caused by failures during development.

MalaCards based summary : Orofacial Cleft, also known as cleft, orofacial, is related to orofacial cleft 1 and orofacial cleft 10. An important gene associated with Orofacial Cleft is LRP6 (LDL Receptor Related Protein 6), and among its related pathways/superpathways are Neural Crest Differentiation and Embryonic and Induced Pluripotent Stem Cells and Lineage-specific Markers. The drugs leucovorin and Folic acid have been mentioned in the context of this disorder. Affiliated tissues include bone, whole blood and pituitary, and related phenotypes are craniofacial and digestive/alimentary

Related Diseases for Orofacial Cleft

Diseases in the Orofacial Cleft family:

Orofacial Cleft 1 Orofacial Cleft 11
Orofacial Cleft 3 Orofacial Cleft 2
Orofacial Cleft 4 Orofacial Cleft 6
Orofacial Cleft 5 Orofacial Cleft 9
Orofacial Cleft 12 Orofacial Cleft 10
Orofacial Cleft 13 Orofacial Cleft 14
Orofacial Cleft 15 Orofacial Cleft 8

Diseases related to Orofacial Cleft via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 216)
# Related Disease Score Top Affiliating Genes
1 orofacial cleft 1 35.3 OFCC1 OFC1
2 orofacial cleft 10 35.2 SUMO1 IRF6
3 orofacial cleft 4 35.2 TP63 SUMO1 OFC4
4 orofacial cleft 8 35.0 TP63 IRF6
5 cleft lip/palate-ectodermal dysplasia syndrome 34.9 TP63 NECTIN1 MSX1 FOXE1
6 cleft lip 34.5 VAX1 TP63 SUMO1 OFC1 NECTIN1 MSX1
7 cleft palate, isolated 34.4 VAX1 TP63 SUMO1 NECTIN1 MSX1 IRF6
8 van der woude syndrome 1 33.9 VAX1 TP63 NECTIN1 MSX1 IRF6 FOXE1
9 popliteal pterygium syndrome 33.7 VAX1 NECTIN1 MSX1 IRF6 FOXE1
10 cleft lip/palate 32.9 TP63 NECTIN1 MSX1 IRF6 DLX4 CDH1
11 cleft lip with or without cleft palate 32.9 OFC1 NECTIN1 MSX1 IRF6 CDH1 BMP4
12 isolated cleft lip 32.4 TP63 NECTIN1 MSX1 IRF6 FOXE1
13 tooth agenesis 31.9 TP63 SUMO1 NECTIN1 MSX1 LRP6 IRF6
14 cleft lip and alveolus 31.5 TP63 NECTIN1 MSX1 IRF6
15 ectodermal dysplasia 31.5 TP63 NECTIN1 MSX1 CDH1
16 chromosome 2q35 duplication syndrome 31.2 TP63 NECTIN1 MSX1 IRF6 BMP4
17 microphthalmia 31.1 VAX1 NECTIN1 LRP6 CDH1 BMP4
18 charge syndrome 30.9 MSX1 FOXE1 BMP4
19 ankyloglossia with or without tooth anomalies 30.8 MSX1 IRF6
20 basal cell carcinoma 30.7 TP63 FOXE1 CDH1 BMP4
21 ankyloblepharon-ectodermal defects-cleft lip/palate 30.3 TP63 IRF6
22 orofacial cleft 6 12.8
23 orofacial cleft 5 12.8
24 orofacial cleft 15 12.8
25 orofacial cleft 11 12.7
26 orofacial cleft 2 12.7
27 orofacial cleft 12 12.7
28 orofacial cleft 9 12.6
29 orofacial cleft 13 12.6
30 orofacial cleft 3 12.6
31 orofacial cleft 14 12.6
32 orofacial clefting syndrome 12.5
33 tooth agenesis, selective, 1 12.3
34 microphthalmia, syndromic 11 11.6
35 split-hand/foot malformation 1 11.6
36 ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 1 11.6
37 microphthalmia, syndromic 6 11.5
38 split-hand/foot malformation 6 11.4
39 split-hand/foot malformation 3 11.4
40 facial clefting, oblique, 1 11.4
41 split-hand/foot malformation 4 11.4
42 rapp-hodgkin syndrome 11.3
43 otofaciocervical syndrome 1 11.3
44 otofaciocervical syndrome 2 11.3
45 coloboma, ocular, with or without hearing impairment, cleft lip/palate, and/or mental retardation 11.2
46 hemifacial microsomia with radial defects 11.2
47 split-hand/foot malformation 1 with sensorineural hearing loss, autosomal recessive 11.2
48 split-hand/foot malformation 5 11.2
49 split hand-foot malformation 11.2
50 lymphoid interstitial pneumonia 10.9 VAX1 TP63 NECTIN1 MSX1 IRF6

Graphical network of the top 20 diseases related to Orofacial Cleft:



Diseases related to Orofacial Cleft

Symptoms & Phenotypes for Orofacial Cleft

MGI Mouse Phenotypes related to Orofacial Cleft:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.85 BMP4 FOXE1 IRF6 LRP6 MSX1 NECTIN1
2 digestive/alimentary MP:0005381 9.61 BMP4 CDH1 FOXE1 IRF6 LRP6 MSX1
3 integument MP:0010771 9.23 BMP4 CDH1 FOXE1 IRF6 LRP6 MSX1

Drugs & Therapeutics for Orofacial Cleft

Drugs for Orofacial Cleft (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 12)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
leucovorin Approved 58-05-9 6006 143
2
Folic acid Approved, Nutraceutical, Vet_approved 59-30-3 6037
3 Hormone Antagonists
4 Hormones
5 Diflucortolone
6 glucocorticoids
7 Diflucortolone valerate
8 Anti-Inflammatory Agents
9 Anesthetics
10 Vitamin B Complex
11 Folate
12 Vitamin B9

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Risk Association of Orofacial Cleft and Glucocorticoids Exposure During Pregnancy: a Meta-analysis Completed NCT03788863 Diflucortolone valerate (BAY866146)
2 Unilateral Cleft Repair in One Surgery With Pure Primary Healing Completed NCT04108416
3 Identification of Genetic Factors Implicated in Orofacial Cleft Using Whole Exome Sequencing GENEPIC Recruiting NCT03065686
4 Three-dimensional Development of the Palate in Bilateral Orofacial Cleft Newborns One Year After Early Neonatal Cheiloplasty: Classic and Geometric Morphometric Evaluation Recruiting NCT03839290
5 Use of Computer Aided Design and 3D Printing for Anesthesiology Management in a Pediatric Patient With Cleft Facial Defect: Pilot Trial Recruiting NCT04422964
6 Use of Computer Aided Design and 3D Printing for Anesthesiology Management in a Pediatric Patient With Cleft Facial Defect Not yet recruiting NCT04422847
7 Genetic Analysis of Neural Tube and Orofacial Cleft Defects in the Irish Population Terminated NCT00341068

Search NIH Clinical Center for Orofacial Cleft

Genetic Tests for Orofacial Cleft

Genetic tests related to Orofacial Cleft:

# Genetic test Affiliating Genes
1 Orofacial Cleft 29

Anatomical Context for Orofacial Cleft

MalaCards organs/tissues related to Orofacial Cleft:

40
Bone, Whole Blood, Pituitary, Heart, Kidney, B Lymphoblasts

Publications for Orofacial Cleft

Articles related to Orofacial Cleft:

(show top 50) (show all 361)
# Title Authors PMID Year
1
Incidence of Gastroesophageal Reflux Disease in Children With Cleft Lip and Palate and an Evaluation of Its Impact on Weight Gain. 61
32149845 2020
2
Non-random distribution of deleterious mutations in the DNA and protein-binding domains of IRF6 are associated with Van Der Woude syndrome. 61
32558391 2020
3
Pregnancy Termination in the Case of an Orofacial Cleft: An Investigation of the Concept of Reproductive Autonomy. 61
32495649 2020
4
Genome-wide Enrichment of De Novo Coding Mutations in Orofacial Cleft Trios. 61
32574564 2020
5
Cleft lip/palate and educational attainment: cause, consequence or correlation? A Mendelian-randomization study. 61
32373937 2020
6
Health Information Seeking Through Social Media and Search Engines by Parents of Children With Orofacial Cleft in Nigeria. 61
31665894 2020
7
Three-dimensional development of the palate in bilateral orofacial cleft newborns 1 year after early neonatal cheiloplasty: Classic and geometric morphometric evaluation. 61
32184075 2020
8
Interferon regulatory factor 6 is required for proper wound healing in vivo. 61
31724286 2020
9
The functional variant of NTN1 contributes to the risk of nonsyndromic cleft lip with or without cleft palate. 61
31780810 2020
10
Breastfeeding Practices Among Mothers of Children With Orofacial Clefts in an African Cohort. 61
32295412 2020
11
Morphological variability in unrepaired bilateral clefts with and without cleft palate evaluated with geometric morphometrics. 61
31792971 2020
12
miRNAs as biomarkers of orofacial clefts: A systematic review. 61
31479540 2020
13
Oral Health-Related Quality of Life in Chinese Children With Orofacial Cleft. 61
32207325 2020
14
Maternal multivitamin intake and orofacial clefts in offspring: Japan Environment and Children's Study (JECS) cohort study. 61
32234746 2020
15
Incidence, Risk Factors, and Mortality Associated With Orofacial Cleft Among Children in Ontario, Canada. 61
32049294 2020
16
Prenatal diagnosis of foetal hydrocephalus and suspected X-linked recessive inheritance of cleft lip in a Chihuahua. 61
31902834 2020
17
Body Mass Index and Association With Caries in School-Aged Children With Orofacial Cleft: A Case-Control Study. 61
31450975 2020
18
Whole genome sequencing of orofacial cleft trios from the Gabriella Miller Kids First Pediatric Research Consortium identifies a new locus on chromosome 21. 61
31848685 2020
19
A retrospective nationwide study of the dental caries experience of New Zealand children with orofacial cleft. 61
31596004 2020
20
Individuals with nonsyndromic orofacial clefts have increased asymmetry of fingerprint patterns. 61
32196525 2020
21
Feeding problems and gastrointestinal diseases in Down syndrome. 61
31784293 2020
22
Intrinsic Differences between the Open Chromatin Regions of Oral and Epidermal Keratinocytes. 61
32548603 2020
23
Nonlinear gene expression-phenotype relationships contribute to variation and clefting in the A/WySn mouse. 61
31469941 2019
24
Neurophysiological changes and chronic pain in cleft patients. 61
31711995 2019
25
Epidemiological characteristic of Orofacial clefts and its associated congenital anomalies: retrospective study. 61
31870360 2019
26
Paramedian Orofacial Cleft. 61
31679595 2019
27
Holoprosencephaly, orofacial cleft, and frontonaso-orbital encephaloceles: Genetic evaluation of a possible new syndrome. 61
31353810 2019
28
The impact of cleft lip and/or palate on parental quality of life: A pilot study. 61
31369974 2019
29
Reconstruction of a Unilateral Alveolar Cleft Using a Customized Allogenic Bone Block and Subsequent Dental Implant Placement in an Adult Patient. 61
31276656 2019
30
Coordination of the Fetal Medicine Institute and the Cleft and Craniofacial Center: Application to Early Management of Infants With Cleft Lip and Palate. 61
31524754 2019
31
Deregulated Adhesion Program in Palatal Keratinocytes of Orofacial Cleft Patients. 61
31652793 2019
32
A novel mutation (c.1010G>T; p.R337L) in TP63 as a cause of split-hand/foot malformation with hypodontia. 61
31420900 2019
33
Frequencies of Different Types of Cleft Lip, Cleft Lip with Palate and Cleft Palate in Bangladeshi Children. 61
31599248 2019
34
Genetic factors define CPO and CLO subtypes of nonsyndromicorofacial cleft. 61
31609978 2019
35
A systematic genetic analysis and visualization of phenotypic heterogeneity among orofacial cleft GWAS signals. 61
31172578 2019
36
Can contamination of the environment by dioxins cause craniofacial defects? 61
31169026 2019
37
Nasolabial outcomes in a nationwide study of orofacial cleft in New Zealand. 61
30849215 2019
38
Surgical, Speech, and Audiologic Outcomes in Patients With Orofacial Cleft and Van der Woude Syndrome. 61
31299749 2019
39
Re: "Orofacial cleft management by short-term surgical missions in South America: literature review". 61
30935819 2019
40
Response to comments on "Orofacial cleft management by short-term surgical missions in South America: literature review". 61
30318114 2019
41
Five decades of orofacial cleft management and research in Brazil. 61
30297262 2019
42
Oral Health-Related Quality of Life and Dental Caries Status in Children With Orofacial Cleft: An Indian Outlook. 61
31198331 2019
43
Patient-Perceived Barriers to Accessing Cleft Care at a Tertiary Referral Center in São Paulo, Brazil. 61
30153749 2019
44
Efficacy of Periconceptional High-Dose Folic Acid in Isolated Orofacial Cleft Prevention: A Systematic Review. 61
31602129 2019
45
Two novel genes TOX3 and COL21A1 in large extended Malay families with nonsyndromic cleft lip and/or palate. 61
30924295 2019
46
Social impact of cleft lip repair on married adults: an uncommon finding from a semi-urban African settlement. 61
30850222 2019
47
A Comparison of Early Versus Late Prenatal Magnetic Resonance Imaging in the Diagnosis of Cleft Palate. 61
30855394 2019
48
Maternal folic acid supplementation reduces the severity of cleft palate in Tgf-β3 null mutant mice. 61
30683931 2019
49
Orthodontic-Surgical Approach for Treating Skeletal Class III Malocclusion With Severe Maxillary Deficiency in Isolated Cleft Palate. 61
29787302 2019
50
Proportion of Orofacial Clefts Attributable to Recognized Risk Factors. 61
29727221 2019

Variations for Orofacial Cleft

ClinVar genetic disease variations for Orofacial Cleft:

6 (show all 21) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 LRP6 NM_002336.3(LRP6):c.4593del (p.Cys1532fs)deletion Pathogenic 225147 rs869320635 12:12274309-12274309 12:12121375-12121375
2 BMP4 NM_001202.6(BMP4):c.*251C>TSNV Conflicting interpretations of pathogenicity 313336 rs573118445 14:54416499-54416499 14:53949781-53949781
3 BMP4 NM_001202.6(BMP4):c.215A>G (p.Gln72Arg)SNV Conflicting interpretations of pathogenicity 313354 rs771047931 14:54418726-54418726 14:53952008-53952008
4 BMP4 NM_001202.6(BMP4):c.*148_*149insATinsertion Uncertain significance 313339 rs796563569 14:54416601-54416602 14:53949883-53949884
5 BMP4 NM_001202.6(BMP4):c.*148_*149insAGinsertion Uncertain significance 313343 rs796563569 14:54416601-54416602 14:53949883-53949884
6 BMP4 NM_001202.6(BMP4):c.*145_*149deldeletion Uncertain significance 313340 rs886050539 14:54416601-54416605 14:53949883-53949887
7 BMP4 NM_001202.6(BMP4):c.*150deldeletion Uncertain significance 313337 rs878985651 14:54416600-54416600 14:53949882-53949882
8 BMP4 NM_001202.6(BMP4):c.*148_*149insAATinsertion Uncertain significance 313342 rs796563569 14:54416601-54416602 14:53949883-53949884
9 BMP4 NM_001202.6(BMP4):c.*149G>ASNV Uncertain significance 313345 rs74495140 14:54416601-54416601 14:53949883-53949883
10 BMP4 NM_001202.6(BMP4):c.*148_*149deldeletion Uncertain significance 313338 rs140085940 14:54416601-54416602 14:53949883-53949884
11 BMP4 NM_001202.6(BMP4):c.*146_*148dupduplication Uncertain significance 313344 rs1555339771 14:54416601-54416602 14:53949883-53949884
12 BMP4 NM_001202.6(BMP4):c.370+12C>TSNV Uncertain significance 313351 rs368426865 14:54418559-54418559 14:53951841-53951841
13 LRP6 NM_002336.3(LRP6):c.4298C>T (p.Ser1433Leu)SNV Uncertain significance 225160 rs869320647 12:12279639-12279639 12:12126705-12126705
14 LRP6 NM_002336.3(LRP6):c.4136G>A (p.Gly1379Asp)SNV Uncertain significance 225159 rs869320646 12:12279801-12279801 12:12126867-12126867
15 LRP6 NM_002336.3(LRP6):c.3365A>C (p.Asp1122Ala)SNV Uncertain significance 225158 rs869320645 12:12300332-12300332 12:12147398-12147398
16 LRP6 NM_002336.3(LRP6):c.2995G>C (p.Gly999Arg)SNV Uncertain significance 225157 rs869320644 12:12302087-12302087 12:12149153-12149153
17 LRP6 NM_002336.3(LRP6):c.2058C>G (p.Ile686Met)SNV Uncertain significance 225156 rs869320643 12:12315348-12315348 12:12162414-12162414
18 LRP6 NM_002336.3(LRP6):c.1620G>T (p.Leu540Phe)SNV Uncertain significance 225155 rs869320642 12:12318155-12318155 12:12165221-12165221
19 LRP6 NM_002336.3(LRP6):c.1004G>T (p.Arg335Leu)SNV Uncertain significance 225154 rs869320641 12:12334346-12334346 12:12181412-12181412
20 BMP4 NM_001202.6(BMP4):c.*148_*149insTinsertion Uncertain significance 313341 rs796563569 14:54416601-54416602 14:53949883-53949884
21 CDH1 NM_004360.5(CDH1):c.88C>A (p.Pro30Thr)SNV Benign 127933 rs139866691 16:68772239-68772239 16:68738336-68738336

Expression for Orofacial Cleft

Search GEO for disease gene expression data for Orofacial Cleft.

Pathways for Orofacial Cleft

Pathways related to Orofacial Cleft according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.34 MSX1 CDH1 BMP4
2 11.05 TP63 MSX1 IRF6 BMP4
3 10.72 NECTIN1 CDH1
4
Show member pathways
10.6 TP63 SUMO1
5 9.86 TP63 IRF6

GO Terms for Orofacial Cleft

Cellular components related to Orofacial Cleft according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nuclear chromatin GO:0000790 9.1 VAX1 TP63 MSX1 IRF6 FOXE1 DLX4
2 apical junction complex GO:0043296 8.96 NECTIN1 CDH1

Biological processes related to Orofacial Cleft according to GeneCards Suite gene sharing:

(show all 19)
# Name GO ID Score Top Affiliating Genes
1 regulation of transcription, DNA-templated GO:0006355 10.08 VAX1 TP63 SUMO1 MSX1 LRP6 IRF6
2 positive regulation of transcription by RNA polymerase II GO:0045944 10.06 TP63 MSX1 LRP6 IRF6 DLX4 BMP4
3 multicellular organism development GO:0007275 10.04 VAX1 TP63 MSX1 LRP6 DLX4 CDH1
4 cell differentiation GO:0030154 10.02 VAX1 TP63 IRF6 FOXE1 DLX4 BMP4
5 negative regulation of transcription, DNA-templated GO:0045892 9.93 TP63 SUMO1 MSX1 FOXE1 BMP4
6 positive regulation of transcription, DNA-templated GO:0045893 9.91 TP63 LRP6 IRF6 FOXE1 CDH1 BMP4
7 negative regulation of transcription by RNA polymerase II GO:0000122 9.91 VAX1 TP63 SUMO1 MSX1 FOXE1 DLX4
8 camera-type eye morphogenesis GO:0048593 9.58 NECTIN1 BMP4
9 embryonic morphogenesis GO:0048598 9.57 MSX1 BMP4
10 anatomical structure formation involved in morphogenesis GO:0048646 9.56 TP63 BMP4
11 epithelial to mesenchymal transition involved in endocardial cushion formation GO:0003198 9.52 MSX1 BMP4
12 cranial skeletal system development GO:1904888 9.51 TP63 FOXE1
13 pituitary gland development GO:0021983 9.5 MSX1 CDH1 BMP4
14 BMP signaling pathway involved in heart development GO:0061312 9.46 MSX1 BMP4
15 odontogenesis of dentin-containing tooth GO:0042475 9.46 TP63 MSX1 LRP6 BMP4
16 embryonic hindlimb morphogenesis GO:0035116 9.43 TP63 MSX1 BMP4
17 cloacal septation GO:0060197 9.4 TP63 BMP4
18 embryonic limb morphogenesis GO:0030326 9.26 TP63 MSX1 LRP6 BMP4
19 roof of mouth development GO:0060021 9.1 VAX1 SUMO1 MSX1 LRP6 IRF6 FOXE1

Molecular functions related to Orofacial Cleft according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 9.43 VAX1 TP63 MSX1 IRF6 FOXE1 DLX4
2 sequence-specific DNA binding GO:0043565 9.1 VAX1 TP63 MSX1 IRF6 FOXE1 DLX4

Sources for Orofacial Cleft

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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