MCID: ORF002
MIFTS: 42

Orofacial Cleft

Categories: Fetal diseases, Genetic diseases, Rare diseases
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Aliases & Classifications for Orofacial Cleft

MalaCards integrated aliases for Orofacial Cleft:

Name: Orofacial Cleft 11 5 14
Cleft, Orofacial 38

Classifications:



External Ids:

Disease Ontology 11 DOID:0050567

Summaries for Orofacial Cleft

Disease Ontology: 11 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 10 and orofacial cleft 5. An important gene associated with Orofacial Cleft is LRP6 (LDL Receptor Related Protein 6), and among its related pathways/superpathways are Embryonic and Induced Pluripotent Stem Cells and Lineage-specific Markers and Development of ureteric collection system. The drugs Difluocortolone and Levoleucovorin have been mentioned in the context of this disorder. Affiliated tissues include whole blood, b lymphoblasts and bone, and related phenotypes are limbs/digits/tail 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 104)
# Related Disease Score Top Affiliating Genes
1 orofacial cleft 10 33.4 SUMO1 OFCC1 MSX1
2 orofacial cleft 5 33.3 OFCC1 MSX1
3 orofacial cleft 1 33.3 OFCC1 OFC1
4 orofacial cleft 4 33.3 TP63 SUMO1 OFC4
5 orofacial cleft 11 33.3 OFCC1 BMP4
6 orofacial cleft 15 33.2 OFCC1 DLX4
7 cleft palate, isolated 33.2 TP63 SUMO1 PRODH OFC1 NECTIN1 MSX1
8 cleft lip 33.1 TP63 SUMO1 OFC3 OFC1 NECTIN1 MSX1
9 cleft lip with or without cleft palate 32.6 OFC1 NECTIN1 MSX1 GDF11
10 cleft lip/palate 32.0 TP63 NECTIN1 MSX1 IRF6 DLX4 BMP4
11 orofacial clefting syndrome 31.3 LRP6 GDF11 FST
12 tooth agenesis 31.3 TP63 SUMO1 NECTIN1 MSX1 LRP6 IRF6
13 isolated cleft lip 31.2 TP63 NECTIN1 MSX1 IRF6
14 van der woude syndrome 31.2 TP63 NECTIN1 MSX1 IRF6 BMP4
15 cleft lip and alveolus 30.9 TP63 NECTIN1 MSX1 IRF6
16 ankyloglossia with or without tooth anomalies 30.6 TP63 MSX1 IRF6
17 atrial heart septal defect 30.4 PRODH MSX1 BMP4
18 orofacial cleft 6 11.7
19 cleft lip/palate-ectodermal dysplasia syndrome 11.7
20 orofacial cleft 8 11.7
21 orofacial cleft 2 11.6
22 orofacial cleft 3 11.6
23 orofacial cleft 9 11.6
24 orofacial cleft 12 11.6
25 tooth agenesis, selective, 1 11.6
26 orofacial cleft 13 11.5
27 orofacial cleft 14 11.5
28 microphthalmia, syndromic 6 11.3
29 otofaciocervical syndrome 1 11.2
30 otofaciocervical syndrome 2, with t-cell deficiency 11.1
31 rapp-hodgkin syndrome 11.1
32 facial clefting, oblique, 1 11.0
33 chromosome 2q35 duplication syndrome 10.6 TP63 NECTIN1 MSX1 LRP6 IRF6 BMP4
34 ectodermal dysplasia 1, hypohidrotic, x-linked 10.6 TP63 NECTIN1 MSX1 BMP4
35 branchiooculofacial syndrome 10.6 OFCC1 MSX1 IRF6 BMP4
36 ectodermal dysplasia 10b, hypohidrotic/hair/tooth type, autosomal recessive 10.6 TP63 NECTIN1 MSX1 BMP4
37 physical disorder 10.6 PRODH MSX1 IRF6 BMP4
38 syngnathia 10.5 MSX1 IRF6 BMP4
39 popliteal pterygium syndrome 10.5 NECTIN1 MSX1 IRF6
40 ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 1 10.5 TP63 NECTIN1 IRF6
41 chromosome 10q23 deletion syndrome 10.5 MSX1 BMP4
42 fissured tongue 10.5 TP63 IRF6
43 ectodermal dysplasia 13, hair/tooth type 10.5 MSX1 LRP6
44 anodontia 10.4 MSX1 LRP6
45 hypothyroidism, thyroidal or athyroidal, with spiky hair and cleft palate 10.4 MSX1 IRF6
46 ankyloblepharon-ectodermal defects-cleft lip/palate 10.3 TP63 IRF6
47 clouston syndrome 10.2 TP63 NECTIN1
48 dental caries 10.2
49 hypertelorism 10.0
50 contractures, pterygia, and spondylocarpotarsal fusion syndrome 1a 10.0

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 limbs/digits/tail MP:0005371 9.8 BMP4 GDF11 IRF6 LRP6 MSX1 PRODH
2 digestive/alimentary MP:0005381 9.76 BMP4 FST GDF11 IRF6 LRP6 MSX1
3 craniofacial MP:0005382 9.65 BMP4 FST GDF11 IRF6 LRP6 MSX1
4 skeleton MP:0005390 9.28 BMP4 FST GDF11 IRF6 LRP6 MSX1

Drugs & Therapeutics for Orofacial Cleft

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

(show all 11)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Difluocortolone Approved, Investigational, Withdrawn 2607-06-9 14445457 11954369
2
Levoleucovorin Approved, Experimental, Investigational 68538-85-2, 58-05-9, 73951-54-9 149436 6006
3
Folic acid Approved, Nutraceutical, Vet_approved 59-30-3 6037
4
Diflucortolone valerate 3058
5 Hormones
6 Hormone Antagonists
7 glucocorticoids
8 Anti-Inflammatory Agents
9 Folate
10 Vitamin B9
11 Vitamin B Complex

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Three-dimensional Development of the Palate in Bilateral Orofacial Cleft Newborns One Year After Early Neonatal Cheiloplasty: Classic and Geometric Morphometric Evaluation Unknown status NCT03839290
2 Risk Association of Orofacial Cleft and Glucocorticoids Exposure During Pregnancy: a Meta-analysis Completed NCT03788863 Diflucortolone valerate (BAY866146)
3 Neural Network to Calculate Morphology of the Cleft Palate to Reduce Cleft Lip and Palate Treatment Burden. Recruiting NCT04342234
4 Identification of Genetic Factors Implicated in Orofacial Cleft Using Whole Exome Sequencing GENEPIC Recruiting NCT03065686
5 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

Anatomical Context for Orofacial Cleft

Organs/tissues related to Orofacial Cleft:

MalaCards : Whole Blood, B Lymphoblasts, Bone, Heart, Pituitary, Kidney

Publications for Orofacial Cleft

Articles related to Orofacial Cleft:

(show top 50) (show all 464)
# Title Authors PMID Year
1
Mutations in GDF11 and the extracellular antagonist, Follistatin, as a likely cause of Mendelian forms of orofacial clefting in humans. 5
31215115 2019
2
Do Orofacial Clefts Impair Breastfeeding and Increase the Prevalence of Anemia? 62
34755566 2023
3
Six-year Burden of Care for Nonsyndromic Unilateral Cleft Lip and Palate Patients: A Comparison Between Cleft Centers and Noncleft Centers. 62
34786981 2023
4
Speech Outcomes of a National Cohort of Children with Orofacial Cleft at 5 and 10 Years of age. 62
34672811 2022
5
Investigation of exposure to heavy metals (Hg, Pb, Cd, Co, and Cr) as the cause of congenital anomaly cases (orofacial cleft) in infants. 62
35748989 2022
6
Inhibition of the 3-hydroxy-3-methyl-glutaryl-CoA reductase diminishes the survival and size of chondrocytes during orofacial morphogenesis in zebrafish. 62
36320166 2022
7
Association Between MTHFD1 1958G > A Variant and non-Syndromic Cleft lip and Palate: An Updated Meta-Analysis. 62
34904448 2022
8
A Narrative Review on Non-Invasive Diagnostic Tools for the Analysis of Dental Arches in Orofacial Cleft Patients. 62
36291469 2022
9
Limited Access to Alveolar Bone Graft Surgery Following Primary Cleft Lip and Palate Repair in Indonesia: A Questionnaire-Based Qualitative Study. 62
36217224 2022
10
A392V and R945X mutations cause orofacial clefts via impairing PTCH1 function. 62
36265746 2022
11
Maternal Stressful Life Events During the Periconceptional Period and Orofacial Clefts: A Systematic Review and Meta-Analysis. 62
35014881 2022
12
Correlation of Dental Anomalies with Cleft Type and Gender in Non-Syndromic Oral Cleft Patients: A Cross-Sectional Study. 62
36121923 2022
13
Null Association Between Isolated Orofacial Clefts and Sleep Duration: A Cohort Study From the Japan Environment and Children's Study. 62
36163681 2022
14
Maternal Cigarette Smoking and Cleft Lip and Palate: A Systematic Review and Meta-Analysis. 62
34569861 2022
15
The usefulness of cone beam computed tomography according to age in cleft lip and palate. 62
36415532 2022
16
Prenatal Diagnosis and Pregnancy Outcomes of Fetuses With Orofacial Cleft: A Retrospective Cohort Study in Two Centres in Hong Kong. 62
36128746 2022
17
The Periodontal Status of Orofacial Cleft Patients: A Systematic Review and Meta-Analysis. 62
36130097 2022
18
Body Dysmorphic Disorder in Adult Patients With an Orofacial Cleft: An Unseen Psychological Burden. 62
36054769 2022
19
Care Barriers for Patients With Nonsyndromic Orofacial Clefts in Saudi Arabia: A Cross-Sectional Study. 62
34189936 2022
20
Chromatin conformation of human oral epithelium can identify orofacial cleft missing functional variants. 62
36008388 2022
21
Prenatal Diagnosis of Cleft and Craniofacial Conditions: An International Analysis of Practice Patterns. 62
35758434 2022
22
Feasibility of Social Media Recruitment for Orofacial Cleft Genetic Research. 62
34121473 2022
23
The Evaluation of FGFR1, FGFR2 and FOXO1 in Orofacial Cleft Tissue. 62
35455561 2022
24
Genome-wide association study of multiethnic nonsyndromic orofacial cleft families identifies novel loci specific to family and phenotypic subtypes. 62
35191549 2022
25
Genome-wide Gene-by-Sex Interaction Studies Identify Novel Nonsyndromic Orofacial Clefts Risk Locus. 62
34689653 2022
26
Analysis of Environmental Exposures for Nonsyndromic Cleft Lip and/or Palate: A Case-Control Study. 62
35865051 2022
27
Mutations in Van Der Woude Families From Ethiopia. 62
34643600 2022
28
Seasonal Variation of Nonsyndromic Orofacial Clefts in Northern Chinese Population. 62
34538782 2022
29
Subphenotypes in Non-Syndromic Orofacial Cleft Patients Based on the Tooth Agenesis Code (TAC). 62
35327809 2022
30
Childhood Experiences and Perspectives of Individuals With Orofacial Clefts: A Qualitative Systematic Review. 62
35254151 2022
31
Cleft Care in a Developing Country: An Assessment of Knowledge and Attitudes of Patients/Parents of Children With an Orofacial Cleft to Orthodontic Treatment. 62
33715465 2022
32
Advances in research regarding the roles of non-coding RNAs in non-syndromic cleft lip with or without cleft palate: A systematic review. 62
34864430 2022
33
Orofacial Cleft and Mandibular Prognathism-Human Genetics and Animal Models. 62
35055138 2022
34
E-liquids and vanillin flavoring disrupts retinoic acid signaling and causes craniofacial defects in Xenopus embryos. 62
34543654 2022
35
Mouse models in palate development and orofacial cleft research: Understanding the crucial role and regulation of epithelial integrity in facial and palate morphogenesis. 62
35461563 2022
36
Case report: Prenatal diagnosis of Ectrodactyly-Ectodermal dysplasia-Cleft syndrome (EEC) in a fetus with cleft lip and polycystic kidney. 62
36386837 2022
37
Genetic markers for non-syndromic orofacial clefts in populations of European ancestry: a meta-analysis. 62
35075162 2022
38
Genome-wide Interaction Study Implicates VGLL2 and Alcohol Exposure and PRL and Smoking in Orofacial Cleft Risk. 62
35223824 2022
39
Investigating the relationship between cancer and orofacial clefts using GWAS significant loci for cancers: A case-control and case-triad study. 62
35990505 2022
40
Correlation between burden and sleep quality in informal caregivers of infants with orofacial cleft. 62
36383793 2022
41
Managing Bilateral Oro-Sino-Orbital Fistulae in the Setting of Bilateral Tessier IV Clefts. 62
34320573 2022
42
Prevalence of malnutrition among children at primary cleft surgery: A cross-sectional analysis of a global database. 62
35265326 2022
43
Consistent downregulation of the cleft lip/palate-associated genes IRF6 and GRHL3 in carcinomas. 62
36457487 2022
44
Long-term treatment outcomes from the perspective of a patient with unilateral cleft lip and palate. 62
34969802 2021
45
Assessment of dental anxiety using modified dental anxiety scale among adults with cleft lip and/or palate. 62
34938052 2021
46
Birth prevalence of orofacial cleft in a tertiary hospital in Riyadh, Saudi Arabia: A retrospective audit. 62
34938037 2021
47
Association between variants around IRF6 and non-syndromic orofacial cleft in Western Han Chinese. 62
34894020 2021
48
A Challenging Period After Repair: Etiology and Follow-Up Rates of the Patients With Cleft Lip and Palate in Intensive Care Unit. 62
34231508 2021
49
Seasonal Influence on the Numbers of Gender-Related Orofacial Cleft Conceptions in the Netherlands. 62
33467910 2021
50
A spatial analysis of birth defects in Texas, 1999-2011. 62
34240569 2021

Variations for Orofacial Cleft

ClinVar genetic disease variations for Orofacial Cleft:

5 (show all 23)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 LRP6 NM_002336.3(LRP6):c.4593del (p.Cys1532fs) DEL Pathogenic
225147 rs869320635 GRCh37: 12:12274309-12274309
GRCh38: 12:12121375-12121375
2 GDF11 NM_005811.5(GDF11):c.893G>A (p.Arg298Gln) SNV Likely Pathogenic
982234 rs1878258280 GRCh37: 12:56143335-56143335
GRCh38: 12:55749551-55749551
3 FST NM_013409.3(FST):c.167G>A (p.Cys56Tyr) SNV Likely Pathogenic
982235 rs1747328996 GRCh37: 5:52778791-52778791
GRCh38: 5:53482961-53482961
4 LRP6 NM_002336.3(LRP6):c.1620G>T (p.Leu540Phe) SNV Uncertain Significance
225155 rs869320642 GRCh37: 12:12318155-12318155
GRCh38: 12:12165221-12165221
5 LRP6 NM_002336.3(LRP6):c.3365A>C (p.Asp1122Ala) SNV Uncertain Significance
225158 rs869320645 GRCh37: 12:12300332-12300332
GRCh38: 12:12147398-12147398
6 LRP6 NM_002336.3(LRP6):c.2058C>G (p.Ile686Met) SNV Uncertain Significance
225156 rs869320643 GRCh37: 12:12315348-12315348
GRCh38: 12:12162414-12162414
7 LRP6 NM_002336.3(LRP6):c.4136G>A (p.Gly1379Asp) SNV Uncertain Significance
225159 rs869320646 GRCh37: 12:12279801-12279801
GRCh38: 12:12126867-12126867
8 LRP6 NM_002336.3(LRP6):c.2995G>C (p.Gly999Arg) SNV Uncertain Significance
225157 rs869320644 GRCh37: 12:12302087-12302087
GRCh38: 12:12149153-12149153
9 LRP6 NM_002336.3(LRP6):c.4298C>T (p.Ser1433Leu) SNV Uncertain Significance
225160 rs869320647 GRCh37: 12:12279639-12279639
GRCh38: 12:12126705-12126705
10 LRP6 NM_002336.3(LRP6):c.1004G>T (p.Arg335Leu) SNV Uncertain Significance
225154 rs869320641 GRCh37: 12:12334346-12334346
GRCh38: 12:12181412-12181412
11 BMP4 NM_001202.6(BMP4):c.*148_*149insAAT INSERT Uncertain Significance
313342 rs796563569 GRCh37: 14:54416601-54416602
GRCh38: 14:53949883-53949884
12 BMP4 NM_001202.6(BMP4):c.*148_*149del DEL Uncertain Significance
313338 rs140085940 GRCh37: 14:54416601-54416602
GRCh38: 14:53949883-53949884
13 BMP4 NM_001202.6(BMP4):c.*148_*149insAT INSERT Uncertain Significance
313339 rs796563569 GRCh37: 14:54416601-54416602
GRCh38: 14:53949883-53949884
14 BMP4 NM_001202.6(BMP4):c.215A>G (p.Gln72Arg) SNV Uncertain Significance
313354 rs771047931 GRCh37: 14:54418726-54418726
GRCh38: 14:53952008-53952008
15 BMP4 NM_001202.6(BMP4):c.*150del DEL Uncertain Significance
313337 rs878985651 GRCh37: 14:54416600-54416600
GRCh38: 14:53949882-53949882
16 BMP4 NM_001202.6(BMP4):c.*145_*149del DEL Uncertain Significance
313340 rs886050539 GRCh37: 14:54416601-54416605
GRCh38: 14:53949883-53949887
17 BMP4 NM_001202.6(BMP4):c.*148_*149insT INSERT Uncertain Significance
313341 rs796563569 GRCh37: 14:54416601-54416602
GRCh38: 14:53949883-53949884
18 BMP4 NM_001202.6(BMP4):c.*149G>A SNV Uncertain Significance
313345 rs74495140 GRCh37: 14:54416601-54416601
GRCh38: 14:53949883-53949883
19 BMP4 NM_001202.6(BMP4):c.*148_*149insAG INSERT Uncertain Significance
313343 rs796563569 GRCh37: 14:54416601-54416602
GRCh38: 14:53949883-53949884
20 BMP4 NM_001202.6(BMP4):c.*146_*148dup DUP Uncertain Significance
313344 rs1555339771 GRCh37: 14:54416601-54416602
GRCh38: 14:53949883-53949884
21 BMP4 NM_001202.6(BMP4):c.370+12C>T SNV Uncertain Significance
313351 rs368426865 GRCh37: 14:54418559-54418559
GRCh38: 14:53951841-53951841
22 BMP4 NM_001202.6(BMP4):c.*251C>T SNV Uncertain Significance
313336 rs573118445 GRCh37: 14:54416499-54416499
GRCh38: 14:53949781-53949781
23 CDH1 NM_004360.5(CDH1):c.88C>A (p.Pro30Thr) SNV Likely Benign
127933 rs139866691 GRCh37: 16:68772239-68772239
GRCh38: 16:68738336-68738336

Expression for Orofacial Cleft

Search GEO for disease gene expression data for Orofacial Cleft.

Pathways for Orofacial Cleft



Pathways directly related to Orofacial Cleft:

# Pathway Source
1 Defective B3GALTL causes PpS Reactome 66

GO Terms for Orofacial Cleft

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

(show all 15)
# Name GO ID Score Top Affiliating Genes
1 skeletal system development GO:0001501 10.02 TP63 GDF11 FST BMP4
2 BMP signaling pathway GO:0030509 9.95 MSX1 FST BMP4
3 cranial skeletal system development GO:1904888 9.84 TP63 IRF6
4 BMP signaling pathway involved in heart development GO:0061312 9.8 MSX1 BMP4
5 embryonic hindlimb morphogenesis GO:0035116 9.8 TP63 MSX1 BMP4
6 ameloblast differentiation GO:0036305 9.73 FST BMP4
7 keratinocyte proliferation GO:0043616 9.73 TP63 IRF6 FST
8 prostatic bud formation GO:0060513 9.71 TP63 BMP4
9 epithelial to mesenchymal transition involved in endocardial cushion formation GO:0003198 9.69 MSX1 BMP4
10 cloacal septation GO:0060197 9.67 BMP4 TP63
11 embryonic limb morphogenesis GO:0030326 9.63 TP63 MSX1 BMP4
12 roof of mouth development GO:0060021 9.56 SUMO1 MSX1 IRF6 GDF11
13 anatomical structure formation involved in morphogenesis GO:0048646 9.52 TP63 BMP4
14 camera-type eye morphogenesis GO:0048593 9.46 NECTIN1 GDF11 BMP4
15 odontogenesis of dentin-containing tooth GO:0042475 9.23 TP63 MSX1 FST BMP4

Sources for Orofacial Cleft

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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