U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Links from OMIM

Orofacial cleft 6, susceptibility to(OFC6)

MedGen UID:
332391
•Concept ID:
C1837213
•
Finding
Synonyms: CLEFT LIP WITH OR WITHOUT CLEFT PALATE, NONSYNDROMIC, 6; OFC6
 
Gene (location): IRF6 (1q32.2)
 
Monarch Initiative: MONDO:0012141
OMIM®: 608864

Definition

Orofacial cleft-6 (OFD6) is characterized by isolated cleft lip or cleft palate or by cleft lip and cleft palate (Rahimov et al., 2008; Pan et al., 2010). For a phenotypic description and a discussion of genetic heterogeneity of nonsyndromic CL/P, see 119530. [from OMIM]

Clinical features

From HPO
Cleft upper lip
MedGen UID:
40327
•Concept ID:
C0008924
•
Congenital Abnormality
A gap or groove in the upper lip. This is a congenital defect resulting from nonfusion of tissues of the lip during embryonal development.
See: Feature record | Search on this feature
Cleft palate
MedGen UID:
756015
•Concept ID:
C2981150
•
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).
See: Feature record | Search on this feature

Professional guidelines

PubMed

Molecular Screening of VAX1 Gene Polymorphisms Uncovered the Genetic Heterogeneity of Nonsyndromic Orofacial Cleft Among Saudi Arabian Patients.
Sabbagh HJ, Innes NPT, Edris Ahmed S, Butali A, Alnamnakani EA, Rabah SM, Hamdan MA, Alhamlan NH, Abdulhameed FD, Hassan MHA, Al Mahdi HB, Alamoudi NM, Al-Aama JY, Alaki SM, Mossey PA
Genet Test Mol Biomarkers 2019 Jan;23(1):45-50. doi: 10.1089/gtmb.2018.0207. PMID: 30633559

Recent clinical studies

Etiology

Caries in children with and without orofacial clefting: A systematic review and meta-analysis.
Grewcock RE, Innes NPT, Mossey PA, Robertson MD
Oral Dis 2022 Jul;28(5):1400-1411. Epub 2022 Mar 22 doi: 10.1111/odi.14183. PMID: 35263806Free PMC Article
DROSHA rs10719 and DICER1 rs3742330 polymorphisms in endometriosis and different diseases: Case-control and review studies.
Cardoso JV, Medeiros R, Dias F, Costa IA, Ferrari R, Berardo PT, Perini JA
Exp Mol Pathol 2021 Apr;119:104616. Epub 2021 Jan 31 doi: 10.1016/j.yexmp.2021.104616. PMID: 33535080
Plant-Based and Plant-Rich Diet Patterns during Gestation: Beneficial Effects and Possible Shortcomings.
Pistollato F, Sumalla Cano S, Elio I, Masias Vergara M, Giampieri F, Battino M
Adv Nutr 2015 Sep;6(5):581-91. Epub 2015 Sep 15 doi: 10.3945/an.115.009126. PMID: 26374180Free PMC Article
Nutrition and genes in the development of orofacial clefting.
Krapels IP, Vermeij-Keers C, Müller M, de Klein A, Steegers-Theunissen RP
Nutr Rev 2006 Jun;64(6):280-8. doi: 10.1111/j.1753-4887.2006.tb00211.x. PMID: 16808114
Progress toward discerning the genetics of cleft lip.
Lidral AC, Moreno LM
Curr Opin Pediatr 2005 Dec;17(6):731-9. doi: 10.1097/01.mop.0000185138.65820.7f. PMID: 16282779Free PMC Article

Diagnosis

Identification of novel susceptibility loci for non-syndromic cleft lip with or without cleft palate.
Ma L, Lou S, Miao Z, Yao S, Yu X, Kan S, Zhu G, Yang F, Zhang C, Zhang W, Wang M, Wang L, Pan Y
J Cell Mol Med 2020 Dec;24(23):13669-13678. Epub 2020 Oct 27 doi: 10.1111/jcmm.15878. PMID: 33108691Free PMC Article
Genetic factors define CPO and CLO subtypes of nonsyndromicorofacial cleft.
Huang L, Jia Z, Shi Y, Du Q, Shi J, Wang Z, Mou Y, Wang Q, Zhang B, Wang Q, Ma S, Lin H, Duan S, Yin B, Lin Y, Wang Y, Jiang D, Hao F, Zhang L, Wang H, Jiang S, Xu H, Yang C, Li C, Li J, Shi B, Yang Z
PLoS Genet 2019 Oct;15(10):e1008357. Epub 2019 Oct 14 doi: 10.1371/journal.pgen.1008357. PMID: 31609978Free PMC Article
Mutations in GDF11 and the extracellular antagonist, Follistatin, as a likely cause of Mendelian forms of orofacial clefting in humans.
Cox TC, Lidral AC, McCoy JC, Liu H, Cox LL, Zhu Y, Anderson RD, Moreno Uribe LM, Anand D, Deng M, Richter CT, Nidey NL, Standley JM, Blue EE, Chong JX, Smith JD, Kirk EP, Venselaar H, Krahn KN, van Bokhoven H, Zhou H, Cornell RA, Glass IA, Bamshad MJ, Nickerson DA, Murray JC, Lachke SA, Thompson TB, Buckley MF, Roscioli T
Hum Mutat 2019 Oct;40(10):1813-1825. Epub 2019 Jun 18 doi: 10.1002/humu.23793. PMID: 31215115Free PMC Article
Whole exome sequencing identifies mutations in 10% of patients with familial non-syndromic cleft lip and/or palate in genes mutated in well-known syndromes.
Basha M, Demeer B, Revencu N, Helaers R, Theys S, Bou Saba S, Boute O, Devauchelle B, Francois G, Bayet B, Vikkula M
J Med Genet 2018 Jul;55(7):449-458. Epub 2018 Mar 2 doi: 10.1136/jmedgenet-2017-105110. PMID: 29500247
Sequencing the GRHL3 Coding Region Reveals Rare Truncating Mutations and a Common Susceptibility Variant for Nonsyndromic Cleft Palate.
Mangold E, Böhmer AC, Ishorst N, Hoebel AK, Gültepe P, Schuenke H, Klamt J, Hofmann A, Gölz L, Raff R, Tessmann P, Nowak S, Reutter H, Hemprich A, Kreusch T, Kramer FJ, Braumann B, Reich R, Schmidt G, Jäger A, Reiter R, Brosch S, Stavusis J, Ishida M, Seselgyte R, Moore GE, Nöthen MM, Borck G, Aldhorae KA, Lace B, Stanier P, Knapp M, Ludwig KU
Am J Hum Genet 2016 Apr 7;98(4):755-62. Epub 2016 Mar 24 doi: 10.1016/j.ajhg.2016.02.013. PMID: 27018475Free PMC Article

Therapy

Caries in children with and without orofacial clefting: A systematic review and meta-analysis.
Grewcock RE, Innes NPT, Mossey PA, Robertson MD
Oral Dis 2022 Jul;28(5):1400-1411. Epub 2022 Mar 22 doi: 10.1111/odi.14183. PMID: 35263806Free PMC Article
Validation of a genome-wide association study implied that SHTIN1 may involve in the pathogenesis of NSCL/P in Chinese population.
Wang Y, Sun Y, Huang Y, Pan Y, Yin A, Shi B, Du X, Ma L, Lan F, Jiang M, Shi J, Zhang L, Xiao X, Zhou Z, Jiang H, Wang L, Yang Y, Cheng J
Sci Rep 2016 Dec 23;6:38872. doi: 10.1038/srep38872. PMID: 28008912Free PMC Article
Plant-Based and Plant-Rich Diet Patterns during Gestation: Beneficial Effects and Possible Shortcomings.
Pistollato F, Sumalla Cano S, Elio I, Masias Vergara M, Giampieri F, Battino M
Adv Nutr 2015 Sep;6(5):581-91. Epub 2015 Sep 15 doi: 10.3945/an.115.009126. PMID: 26374180Free PMC Article
The maternal homocysteine pathway is influenced by riboflavin intake and MTHFR polymorphisms without affecting the risk of orofacial clefts in the offspring.
Vujkovic M, Steegers EA, van Meurs J, Yazdanpanah N, van Rooij IA, Uitterlinden AG, Steegers-Theunissen RP
Eur J Clin Nutr 2010 Mar;64(3):266-73. Epub 2009 Nov 25 doi: 10.1038/ejcn.2009.138. PMID: 19935819
Fine mapping of 39 ESTs on human chromosome 6p23-p25.
Olavesen MG, Bentley E, Mason RV, Stephens RJ, Ragoussis J
Genomics 1997 Dec 1;46(2):303-6. doi: 10.1006/geno.1997.5032. PMID: 9417921

Prognosis

Genome-Wide Association Study (GWAS) of dental caries in diverse populations.
Alotaibi RN, Howe BJ, Chernus JM, Mukhopadhyay N, Sanchez C, Deleyiannis FWB, Neiswanger K, Padilla C, Poletta FA, Orioli IM, Buxó CJ, Hecht JT, Wehby GL, Long RE, Vieira AR, Weinberg SM, Shaffer JR, Moreno Uribe LM, Marazita ML
BMC Oral Health 2021 Jul 26;21(1):377. doi: 10.1186/s12903-021-01670-5. PMID: 34311721Free PMC Article
Mutations in GDF11 and the extracellular antagonist, Follistatin, as a likely cause of Mendelian forms of orofacial clefting in humans.
Cox TC, Lidral AC, McCoy JC, Liu H, Cox LL, Zhu Y, Anderson RD, Moreno Uribe LM, Anand D, Deng M, Richter CT, Nidey NL, Standley JM, Blue EE, Chong JX, Smith JD, Kirk EP, Venselaar H, Krahn KN, van Bokhoven H, Zhou H, Cornell RA, Glass IA, Bamshad MJ, Nickerson DA, Murray JC, Lachke SA, Thompson TB, Buckley MF, Roscioli T
Hum Mutat 2019 Oct;40(10):1813-1825. Epub 2019 Jun 18 doi: 10.1002/humu.23793. PMID: 31215115Free PMC Article
Sequencing the GRHL3 Coding Region Reveals Rare Truncating Mutations and a Common Susceptibility Variant for Nonsyndromic Cleft Palate.
Mangold E, Böhmer AC, Ishorst N, Hoebel AK, Gültepe P, Schuenke H, Klamt J, Hofmann A, Gölz L, Raff R, Tessmann P, Nowak S, Reutter H, Hemprich A, Kreusch T, Kramer FJ, Braumann B, Reich R, Schmidt G, Jäger A, Reiter R, Brosch S, Stavusis J, Ishida M, Seselgyte R, Moore GE, Nöthen MM, Borck G, Aldhorae KA, Lace B, Stanier P, Knapp M, Ludwig KU
Am J Hum Genet 2016 Apr 7;98(4):755-62. Epub 2016 Mar 24 doi: 10.1016/j.ajhg.2016.02.013. PMID: 27018475Free PMC Article
Susceptibility to DNA damage as a molecular mechanism for non-syndromic cleft lip and palate.
Kobayashi GS, Alvizi L, Sunaga DY, Francis-West P, Kuta A, Almada BV, Ferreira SG, de Andrade-Lima LC, Bueno DF, Raposo-Amaral CE, Menck CF, Passos-Bueno MR
PLoS One 2013;8(6):e65677. Epub 2013 Jun 12 doi: 10.1371/journal.pone.0065677. PMID: 23776525Free PMC Article
Association between C677T and A1298C MTHFR gene polymorphism and nonsyndromic orofacial clefts in the Turkish population: a case-parent study.
Semiç-Jusufagiç A, Bircan R, Çelebiler Ö, Erdim M, Akarsu N, Elçioğlu NH
Turk J Pediatr 2012 Nov-Dec;54(6):617-25. PMID: 23692788

Clinical prediction guides

Genome-Wide Association Study (GWAS) of dental caries in diverse populations.
Alotaibi RN, Howe BJ, Chernus JM, Mukhopadhyay N, Sanchez C, Deleyiannis FWB, Neiswanger K, Padilla C, Poletta FA, Orioli IM, Buxó CJ, Hecht JT, Wehby GL, Long RE, Vieira AR, Weinberg SM, Shaffer JR, Moreno Uribe LM, Marazita ML
BMC Oral Health 2021 Jul 26;21(1):377. doi: 10.1186/s12903-021-01670-5. PMID: 34311721Free PMC Article
Identification of novel susceptibility loci for non-syndromic cleft lip with or without cleft palate.
Ma L, Lou S, Miao Z, Yao S, Yu X, Kan S, Zhu G, Yang F, Zhang C, Zhang W, Wang M, Wang L, Pan Y
J Cell Mol Med 2020 Dec;24(23):13669-13678. Epub 2020 Oct 27 doi: 10.1111/jcmm.15878. PMID: 33108691Free PMC Article
Genetic factors define CPO and CLO subtypes of nonsyndromicorofacial cleft.
Huang L, Jia Z, Shi Y, Du Q, Shi J, Wang Z, Mou Y, Wang Q, Zhang B, Wang Q, Ma S, Lin H, Duan S, Yin B, Lin Y, Wang Y, Jiang D, Hao F, Zhang L, Wang H, Jiang S, Xu H, Yang C, Li C, Li J, Shi B, Yang Z
PLoS Genet 2019 Oct;15(10):e1008357. Epub 2019 Oct 14 doi: 10.1371/journal.pgen.1008357. PMID: 31609978Free PMC Article
Plant-Based and Plant-Rich Diet Patterns during Gestation: Beneficial Effects and Possible Shortcomings.
Pistollato F, Sumalla Cano S, Elio I, Masias Vergara M, Giampieri F, Battino M
Adv Nutr 2015 Sep;6(5):581-91. Epub 2015 Sep 15 doi: 10.3945/an.115.009126. PMID: 26374180Free PMC Article
Susceptibility to DNA damage as a molecular mechanism for non-syndromic cleft lip and palate.
Kobayashi GS, Alvizi L, Sunaga DY, Francis-West P, Kuta A, Almada BV, Ferreira SG, de Andrade-Lima LC, Bueno DF, Raposo-Amaral CE, Menck CF, Passos-Bueno MR
PLoS One 2013;8(6):e65677. Epub 2013 Jun 12 doi: 10.1371/journal.pone.0065677. PMID: 23776525Free PMC Article

Recent systematic reviews

Caries in children with and without orofacial clefting: A systematic review and meta-analysis.
Grewcock RE, Innes NPT, Mossey PA, Robertson MD
Oral Dis 2022 Jul;28(5):1400-1411. Epub 2022 Mar 22 doi: 10.1111/odi.14183. PMID: 35263806Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Reviews

    Related information

    • ClinVar
      Related medical variations
    • Gene
      Related information in NCBI Gene
    • GTR
      Related information in GTR
    • GTR(Clinical)
      Clinical tests in GTR
    • OMIM
      Related records in OMIM
    • OMIM(Genes)
      OMIM records containing genes associated with phenotypes registered in MedGen
    • PMC Articles
      Related information in PubMed Central Links
    • PubMed
      Related literature resources in PubMed
    • PubMed (OMIM)
      Related literature resources in PubMed

    Recent activity

    Clear Turn Off Turn On

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...