MCID: ORF053
MIFTS: 31

Orofacial Clefting Syndrome

Categories: Fetal diseases, Rare diseases

Aliases & Classifications for Orofacial Clefting Syndrome

MalaCards integrated aliases for Orofacial Clefting Syndrome:

Name: Orofacial Clefting Syndrome 58
Orofacial Clefting 6

Classifications:

Orphanet: 58  
Developmental anomalies during embryogenesis


External Ids:

Orphanet 58 ORPHA139039

Summaries for Orofacial Clefting Syndrome

MalaCards based summary : Orofacial Clefting Syndrome, also known as orofacial clefting, is related to cleft palate, isolated and orofacial cleft. An important gene associated with Orofacial Clefting Syndrome is LRP6 (LDL Receptor Related Protein 6). The drugs Levoleucovorin and Folic acid have been mentioned in the context of this disorder. Affiliated tissues include skin, eye and whole blood, and related phenotypes are craniofacial and digestive/alimentary

Related Diseases for Orofacial Clefting Syndrome

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

(show top 50) (show all 71)
# Related Disease Score Top Affiliating Genes
1 cleft palate, isolated 30.2 LRP6 FST
2 orofacial cleft 29.4 LRP6 GDF11 FST
3 split-hand/foot malformation 6 11.2
4 split-hand/foot malformation 3 11.2
5 split-hand/foot malformation 4 11.2
6 microphthalmia, syndromic 11 11.2
7 vertebral hypersegmentation and orofacial anomalies 11.1
8 coloboma, ocular, with or without hearing impairment, cleft lip/palate, and/or mental retardation 11.1
9 split-hand/foot malformation 1 11.1
10 split-hand/foot malformation 1 with sensorineural hearing loss, autosomal recessive 11.1
11 facial clefting, oblique, 1 11.1
12 split-hand/foot malformation 5 11.1
13 split hand-foot malformation 11.1
14 cleft lip with or without cleft palate 10.6
15 van der woude syndrome 1 10.3
16 hypertelorism 10.2
17 tooth agenesis 10.2
18 orofacial cleft 1 10.1
19 learning disability 10.1
20 irf6-related disorders 10.1
21 cleft lip 10.0
22 cleft lip/palate 10.0
23 tooth agenesis, selective, 1 9.9
24 popliteal pterygium syndrome 9.9
25 epicanthus 9.9
26 gastric cancer, hereditary diffuse 9.9
27 treacher collins syndrome 1 9.9
28 marfan syndrome 9.9
29 pectus excavatum 9.9
30 ulnar-mammary syndrome 9.9
31 uvula, bifid 9.9
32 velocardiofacial syndrome 9.9
33 celiac disease 1 9.9
34 corpus callosum, agenesis of 9.9
35 phenylketonuria 9.9
36 pierre robin syndrome 9.9
37 thrombocytopenia-absent radius syndrome 9.9
38 orofaciodigital syndrome i 9.9
39 fryns microphthalmia syndrome 9.9
40 cleft palate, cardiac defects, and mental retardation 9.9
41 phace association 9.9
42 orofacial cleft 5 9.9
43 gastric cancer 9.9
44 alacrima, achalasia, and mental retardation syndrome 9.9
45 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 9.9
46 orofacial cleft 15 9.9
47 chromosome 15q14 deletion syndrome 9.9
48 autism spectrum disorder 9.9
49 ptosis 9.9
50 acrofacial dysostosis 9.9

Graphical network of the top 20 diseases related to Orofacial Clefting Syndrome:



Diseases related to Orofacial Clefting Syndrome

Symptoms & Phenotypes for Orofacial Clefting Syndrome

MGI Mouse Phenotypes related to Orofacial Clefting Syndrome:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.54 FST GDF11 LRP6
2 digestive/alimentary MP:0005381 9.5 FST GDF11 LRP6
3 respiratory system MP:0005388 9.43 FST GDF11 LRP6
4 skeleton MP:0005390 9.33 FST GDF11 LRP6
5 taste/olfaction MP:0005394 8.96 FST GDF11
6 vision/eye MP:0005391 8.8 FST GDF11 LRP6

Drugs & Therapeutics for Orofacial Clefting Syndrome

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

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

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 Identification of Genetic Factors Implicated in Orofacial Cleft Using Whole Exome Sequencing GENEPIC Recruiting NCT03065686
4 Genetic Analysis of Neural Tube and Orofacial Cleft Defects in the Irish Population Terminated NCT00341068

Search NIH Clinical Center for Orofacial Clefting Syndrome

Genetic Tests for Orofacial Clefting Syndrome

Anatomical Context for Orofacial Clefting Syndrome

MalaCards organs/tissues related to Orofacial Clefting Syndrome:

40
Skin, Eye, Whole Blood, Cortex, B Lymphoblasts

Publications for Orofacial Clefting Syndrome

Articles related to Orofacial Clefting Syndrome:

(show top 50) (show all 324)
# 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. 6 61
31215115 2019
2
Impact of Maternal Smoking on Nonsyndromic Clefts: Sex-Specific Associations With Side and Laterality. 61
32844678 2021
3
Cleft Lip and Palate in Ectodermal Dysplasia. 61
32864997 2021
4
The power of zebrafish models for understanding the co-occurrence of craniofacial and limb disorders. 61
33393730 2021
5
TP63-mutation as a cause of prenatal lethal multicystic dysplastic kidneys. 61
32881366 2020
6
Parents of Children With Nonsyndromic Orofacial Clefting Show Altered Palate Shape. 61
33111571 2020
7
Msx1 deficiency interacts with hypoxia and induces a morphogenetic regulation during mouse lip development. 61
32467233 2020
8
Cleft lip and cleft palate in Esrp1 knockout mice is associated with alterations in epithelial-mesenchymal crosstalk. 61
32253237 2020
9
CDH1 Mutation Distribution and Type Suggests Genetic Differences between the Etiology of Orofacial Clefting and Gastric Cancer. 61
32260281 2020
10
40th Annual David W Smith Workshop on Malformations and Morphogenesis: Abstracts of the 2019 Annual Meeting. 61
32153128 2020
11
Analysis of zebrafish periderm enhancers facilitates identification of a regulatory variant near human KRT8/18. 61
32031521 2020
12
Finding the Unicorn, a New Mouse Model of Midfacial Clefting. 61
31940751 2020
13
Individuals with nonsyndromic orofacial clefts have increased asymmetry of fingerprint patterns. 61
32196525 2020
14
Case Report of Floating-Harbor Syndrome With Bilateral Cleft Lip. 61
31248274 2020
15
Tissue engineering strategies combining molecular targets against inflammation and fibrosis, and umbilical cord blood stem cells to improve hampered muscle and skin regeneration following cleft repair. 61
31104334 2020
16
Nonlinear gene expression-phenotype relationships contribute to variation and clefting in the A/WySn mouse. 61
31469941 2019
17
Nucleic acid methylation and orofacial morphogenesis. 61
31385455 2019
18
A systematic genetic analysis and visualization of phenotypic heterogeneity among orofacial cleft GWAS signals. 61
31172578 2019
19
New Causal Candidate Genes and Enhancers Linked to Orofacial Clefting Identified. 61
31355538 2019
20
Characteristics of Orofacial Clefting in Hawai'i. 61
31463475 2019
21
Regulatory Mechanisms of Soft Palate Development and Malformations. 61
31150594 2019
22
Deletions and loss-of-function variants in TP63 associated with orofacial clefting. 61
30850703 2019
23
Association Studies Between Regulatory Regions of IRF6/TP63 Genes and Nonsyndromic Oral Clefts. 61
30419764 2019
24
Van der Woude Syndrome With a Novel Mutation in the IRF6 Gene. 61
31299817 2019
25
The TFAP2A-IRF6-GRHL3 genetic pathway is conserved in neurulation. 61
30689861 2019
26
p63 establishes epithelial enhancers at critical craniofacial development genes. 61
31049400 2019
27
A cleft lip and palate gene, Irf6, is involved in osteoblast differentiation of craniofacial bone. 61
30684382 2019
28
Systems genetics of nonsyndromic orofacial clefting provides insights into its complex aetiology. 61
30254216 2019
29
Correlation between Type of Clefting and the Incidence of Otitis Media among Children with Lip and/or Palate Clefts. 61
31722340 2019
30
Associations between Orofacial Clefting and Neonatal Abstinence Syndrome. 61
30859050 2019
31
IRF6 and AP2A Interaction Regulates Epidermal Development. 61
29913133 2018
32
Olfactory function in patients with nonsyndromic orofacial clefts and their unaffected relatives. 61
30345654 2018
33
Knockdown of Crispld2 in zebrafish identifies a novel network for nonsyndromic cleft lip with or without cleft palate candidate genes. 61
29899370 2018
34
Patterns of Orofacial Clefting in New York City From 1983 to 2010: Trends by Racial Background, Birthplace, and Public Health Strategies. 61
29665339 2018
35
Oral-Health-Related Quality of Life in Children and Adolescents. 61
30213350 2018
36
Receptive and expressive language characteristics of school-aged children with non-syndromic cleft lip and/or palate. 61
29968398 2018
37
Pbx loss in cranial neural crest, unlike in epithelium, results in cleft palate only and a broader midface. 61
29797482 2018
38
Nonsyndromic cleft palate: An association study at GWAS candidate loci in a multiethnic sample. 61
29498243 2018
39
Identification of sonic hedgehog-regulated genes and biological processes in the cranial neural crest mesenchyme by comparative transcriptomics. 61
29945554 2018
40
Soft tissue nasal asymmetry as an indicator of orofacial cleft predisposition. 61
29663709 2018
41
High-Resolution Epigenomic Atlas of Human Embryonic Craniofacial Development. 61
29719267 2018
42
GWAS reveals loci associated with velopharyngeal dysfunction. 61
29855589 2018
43
MRPL53, a New Candidate Gene for Orofacial Clefting, Identified Using an eQTL Approach. 61
29053389 2018
44
A Genome-Wide Search for Gene-Environment Effects in Isolated Cleft Lip with or without Cleft Palate Triads Points to an Interaction between Maternal Periconceptional Vitamin Use and Variants in ESRRG. 61
29535761 2018
45
Burden of Orofacial Clefting in India, 2016: A Global Burden of Disease Approach. 61
29963432 2018
46
Common basis for orofacial clefting and cortical interneuronopathy. 61
29317601 2018
47
Expanding the phenotypic spectrum of TP63-related disorders including the first set of monozygotic twins. 61
29130604 2018
48
Six NSCL/P Loci Show Associations With Normal-Range Craniofacial Variation. 61
30410503 2018
49
Testing the face shape hypothesis in twins discordant for nonsyndromic orofacial clefting. 61
28884971 2017
50
Hypertelorism and Orofacial Clefting Revisited: An Anthropometric Investigation. 61
27505181 2017

Variations for Orofacial Clefting Syndrome

ClinVar genetic disease variations for Orofacial Clefting Syndrome:

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

Expression for Orofacial Clefting Syndrome

Search GEO for disease gene expression data for Orofacial Clefting Syndrome.

Pathways for Orofacial Clefting Syndrome

GO Terms for Orofacial Clefting Syndrome

Cellular components related to Orofacial Clefting Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular region GO:0005576 8.8 LRP6 GDF11 FST

Biological processes related to Orofacial Clefting Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 skeletal system development GO:0001501 9.26 GDF11 FST
2 roof of mouth development GO:0060021 9.16 LRP6 GDF11
3 negative regulation of cell differentiation GO:0045596 8.96 GDF11 FST
4 odontogenesis of dentin-containing tooth GO:0042475 8.62 LRP6 FST

Sources for Orofacial Clefting Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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