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Orofacial cleft 1(OFC1)

MedGen UID:
349303
Concept ID:
C1861537
Disease or Syndrome
Synonyms: CLEFT LIP WITH OR WITHOUT CLEFT PALATE, NONSYNDROMIC, 1; Nonsyndromic Cleft Lip/Palate; OFC1; OROFACIAL CLEFT, NONSYNDROMIC
 
Monarch Initiative: MONDO:0007335
OMIM®: 119530

Definition

Nonsyndromic cleft lip with or without cleft palate is a complex disease with a wide phenotypic spectrum ranging from notches of the vermilion and/or grooves in the philtrum to complete unilateral and bilateral clefts of the lip and palate (summary by Neiswanger et al., 2007). Genetic Heterogeneity of Orofacial Cleft Isolated cleft lip with or without cleft palate (CL/P) is genetically heterogeneous. The OFC1 locus has been mapped to chromosome 6p24. Other CL/P loci have been mapped to 2p13 (OFC2; 602966), 19q13 (OFC3; 600757), 4q (OFC4; 608371), 13q33.1-q34 (OFC9; 610361), 8q24.3 (OFC12; 612858), and 1p33 (OFC13; 613857). OFC5 (608874) is caused by mutation in the MSX1 gene (142983) on 4p16; OFC6 (608864) is associated with variation in an enhancer of the IRF6 gene (607199) on 1q; OFC7 (see 225060) is associated with mutation in the NECTIN1 gene (600644) on 11q23; OFC8 (618149) is caused by mutation in the TP63 gene (603273) on 3q28; OFC10 (613705) is associated with haploinsufficiency of the SUMO1 gene (601912) on 2q33; OFC11 (600625) is caused by mutation in the BMP4 gene (112262) on 14q22; OFC14 (615892) is associated with a 273-kb deleted region on 1p31; and OFC15 (616788) is caused by mutation in the DLX4 gene (601911) on 17q21. A common polymorphism in the MTR gene (156570.0008) has been associated with susceptibility to orofacial clefting. Cleft lip with or without cleft palate has been found in association with gastric cancer (see 137215) in individuals with mutation in the CDH1 gene (192090). [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.
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).

Professional guidelines

PubMed

Wang X, Yang X, Huang P, Meng X, Bian Z, Meng L
Ann N Y Acad Sci 2022 Apr;1510(1):167-179. Epub 2021 Dec 24 doi: 10.1111/nyas.14735. PMID: 34951699
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
Miller SF, Weinberg SM, Nidey NL, Defay DK, Marazita ML, Wehby GL, Moreno Uribe LM
J Anat 2014 Jun;224(6):688-709. Epub 2014 Apr 16 doi: 10.1111/joa.12182. PMID: 24738728Free PMC Article

Recent clinical studies

Etiology

Marazita ML
Curr Top Dev Biol 2023;152:169-192. Epub 2022 Nov 14 doi: 10.1016/bs.ctdb.2022.10.006. PMID: 36707211
Cáceres-Rojas G, Salamanca C, Krause BJ, Recabarren AS, Recabarren PA, Pantoja R, Leiva N, Pardo R, Santos JL, Suazo J
Epigenomics 2020 Oct;12(20):1783-1791. Epub 2020 Nov 4 doi: 10.2217/epi-2020-0021. PMID: 33147056
Suhl J, Leonard S, Weyer P, Rhoads A, Siega-Riz AM, Renée Anthony T, Burns TL, Conway KM, Langlois PH, Romitti PA
Birth Defects Res 2018 Nov 15;110(19):1455-1467. Epub 2018 Oct 27 doi: 10.1002/bdr2.1386. PMID: 30367712Free PMC Article
Cardoso EF, Martelli DR, Machado RA, Coletta RD, de Souza JD, Barbosa FT, de Figueiredo MF, Coelho LG, Martelli-Júnior H
Med Oral Patol Oral Cir Bucal 2018 Jan 1;23(1):e44-e48. doi: 10.4317/medoral.22132. PMID: 29274157Free PMC Article
Sabbagh HJ, Hassan MH, Innes NP, Elkodary HM, Little J, Mossey PA
PLoS One 2015;10(3):e0116963. Epub 2015 Mar 11 doi: 10.1371/journal.pone.0116963. PMID: 25760440Free PMC Article

Diagnosis

Schuler CF 4th, O'Shea KM, Troost JP, Kaul B, Launius CM, Cannon J, Manthei DM, Freigeh GE, Sanders GM, Hogan SP, Lukacs NW, Baker JR Jr
J Clin Invest 2023 Aug 15;133(16) doi: 10.1172/JCI168965. PMID: 37402149Free PMC Article
Navarro Sanchez ML, Swartz MD, Langlois PH, Canfield MA, Agopian AJ
Cleft Palate Craniofac J 2023 Jul;60(7):789-803. Epub 2022 Feb 28 doi: 10.1177/10556656221080932. PMID: 35225696Free PMC Article
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
Ansen-Wilson LJ, Everson JL, Fink DM, Kietzman HW, Sullivan R, Lipinski RJ
Transl Psychiatry 2018 Jan 10;8(1):8. doi: 10.1038/s41398-017-0057-7. PMID: 29317601Free PMC Article
Phan M, Conte F, Khandelwal KD, Ockeloen CW, Bartzela T, Kleefstra T, van Bokhoven H, Rubini M, Zhou H, Carels CE
Hum Genet 2016 Dec;135(12):1299-1327. Epub 2016 Oct 3 doi: 10.1007/s00439-016-1733-z. PMID: 27699475Free PMC Article

Therapy

Howe LJ, Hemani G, Lesseur C, Gaborieau V, Ludwig KU, Mangold E, Brennan P, Ness AR, St Pourcain B, Davey Smith G, Lewis SJ
Genet Epidemiol 2020 Nov;44(8):924-933. Epub 2020 Jul 24 doi: 10.1002/gepi.22343. PMID: 32710482Free PMC Article
Suhl J, Leonard S, Weyer P, Rhoads A, Siega-Riz AM, Renée Anthony T, Burns TL, Conway KM, Langlois PH, Romitti PA
Birth Defects Res 2018 Nov 15;110(19):1455-1467. Epub 2018 Oct 27 doi: 10.1002/bdr2.1386. PMID: 30367712Free PMC Article
Suhl J, Romitti PA, Rocheleau C, Cao Y, Burns TL, Conway K, Bell EM, Stewart P, Langlois P; National Birth Defects Prevention Study
J Occup Environ Hyg 2018 Sep;15(9):641-653. doi: 10.1080/15459624.2018.1484127. PMID: 29993348Free PMC Article
Sabbagh HJ, Hassan MH, Innes NP, Elkodary HM, Little J, Mossey PA
PLoS One 2015;10(3):e0116963. Epub 2015 Mar 11 doi: 10.1371/journal.pone.0116963. PMID: 25760440Free PMC Article
Zhao M, Ren Y, Shen L, Zhang Y, Zhou B
PLoS One 2014;9(3):e88242. Epub 2014 Mar 21 doi: 10.1371/journal.pone.0088242. PMID: 24658649Free PMC Article

Prognosis

Schuler CF 4th, O'Shea KM, Troost JP, Kaul B, Launius CM, Cannon J, Manthei DM, Freigeh GE, Sanders GM, Hogan SP, Lukacs NW, Baker JR Jr
J Clin Invest 2023 Aug 15;133(16) doi: 10.1172/JCI168965. PMID: 37402149Free PMC Article
Ip KI, Sisk LM, Horien C, Conley MI, Rapuano KM, Rosenberg MD, Greene AS, Scheinost D, Constable RT, Casey BJ, Baskin-Sommers A, Gee DG
J Cogn Neurosci 2022 Sep 1;34(10):1810-1841. doi: 10.1162/jocn_a_01826. PMID: 35104356
Fell M, Russell C, Medina J, Gillgrass T, Chummun S, Cobb ARM, Sandy J, Wren Y, Wills A, Lewis SJ
PLoS One 2021;16(11):e0259820. Epub 2021 Nov 24 doi: 10.1371/journal.pone.0259820. PMID: 34818369Free PMC Article
Schwarz SJ, Brandenburg LS, Weingart JV, Schupp W, Füssinger MA, Pantke CF, Beck RL, Metzger MC
Laryngoscope 2021 Nov;131(11):E2764-E2769. Epub 2021 Jun 18 doi: 10.1002/lary.29602. PMID: 34142721
Tian M, Xiao L, Jian N, Wei X, Liu S, Zhao H, Li G, Zhang S, Liang W, Lin N, Lin X
Prenat Diagn 2019 Sep;39(10):883-889. Epub 2019 Jul 23 doi: 10.1002/pd.5499. PMID: 31169321

Clinical prediction guides

Schuler CF 4th, O'Shea KM, Troost JP, Kaul B, Launius CM, Cannon J, Manthei DM, Freigeh GE, Sanders GM, Hogan SP, Lukacs NW, Baker JR Jr
J Clin Invest 2023 Aug 15;133(16) doi: 10.1172/JCI168965. PMID: 37402149Free PMC Article
Mukhopadhyay N, Feingold E, Moreno-Uribe L, Wehby G, Valencia-Ramirez LC, Restrepo Muñeton CP, Padilla C, Deleyiannis F, Christensen K, Poletta FA, Orioli IM, Hecht JT, Buxó CJ, Butali A, Adeyemo WL, Vieira AR, Shaffer JR, Murray JC, Weinberg SM, Leslie EJ, Marazita ML
Genet Epidemiol 2022 Apr;46(3-4):182-198. Epub 2022 Feb 22 doi: 10.1002/gepi.22447. PMID: 35191549Free PMC Article
Suhl J, Leonard S, Weyer P, Rhoads A, Siega-Riz AM, Renée Anthony T, Burns TL, Conway KM, Langlois PH, Romitti PA
Birth Defects Res 2018 Nov 15;110(19):1455-1467. Epub 2018 Oct 27 doi: 10.1002/bdr2.1386. PMID: 30367712Free PMC Article
Cardoso EF, Martelli DR, Machado RA, Coletta RD, de Souza JD, Barbosa FT, de Figueiredo MF, Coelho LG, Martelli-Júnior H
Med Oral Patol Oral Cir Bucal 2018 Jan 1;23(1):e44-e48. doi: 10.4317/medoral.22132. PMID: 29274157Free PMC Article
Panamonta V, Pradubwong S, Panamonta M, Chowchuen B
J Med Assoc Thai 2015 Aug;98 Suppl 7:S11-21. PMID: 26742364

Recent systematic reviews

Imani MM, Safaei M, Lopez-Jornet P, Sadeghi M
Int Orthod 2019 Sep;17(3):437-445. Epub 2019 Jul 22 doi: 10.1016/j.ortho.2019.06.026. PMID: 31345669
Phan M, Conte F, Khandelwal KD, Ockeloen CW, Bartzela T, Kleefstra T, van Bokhoven H, Rubini M, Zhou H, Carels CE
Hum Genet 2016 Dec;135(12):1299-1327. Epub 2016 Oct 3 doi: 10.1007/s00439-016-1733-z. PMID: 27699475Free PMC Article
Panamonta V, Pradubwong S, Panamonta M, Chowchuen B
J Med Assoc Thai 2015 Aug;98 Suppl 7:S22-7. PMID: 26742365
Panamonta V, Pradubwong S, Panamonta M, Chowchuen B
J Med Assoc Thai 2015 Aug;98 Suppl 7:S11-21. PMID: 26742364
Sabbagh HJ, Hassan MH, Innes NP, Elkodary HM, Little J, Mossey PA
PLoS One 2015;10(3):e0116963. Epub 2015 Mar 11 doi: 10.1371/journal.pone.0116963. PMID: 25760440Free PMC Article

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