Editing Cleft lip and cleft palate (section)

===Genetics===
Genetic factors contributing to cleft lip and cleft palate formation have been identified for some syndromic cases. Many clefts run in families, even though in some cases there does not seem to be an identifiable syndrome present.<ref>{{cite journal | vauthors = Beaty TH, Ruczinski I, Murray JC, Marazita ML, Munger RG, Hetmanski JB, Murray T, Redett RJ, Fallin MD, Liang KY, Wu T, Patel PJ, Jin SC, Zhang TX, Schwender H, Wu-Chou YH, Chen PK, Chong SS, Cheah F, Yeow V, Ye X, Wang H, Huang S, Jabs EW, Shi B, Wilcox AJ, Lie RT, Jee SH, Christensen K, Doheny KF, Pugh EW, Ling H, Scott AF | title = Evidence for gene-environment interaction in a genome wide study of nonsyndromic cleft palate | journal = Genetic Epidemiology | volume = 35 | issue = 6 | pages = 469–478 | date = September 2011 | pmid = 21618603 | pmc = 3180858 | doi = 10.1002/gepi.20595 }}</ref> A number of genes are involved including [[cleft lip and palate transmembrane protein 1]] and [[GAD1]],<ref name="Kanno2004">{{cite journal | vauthors = Kanno K, Suzuki Y, Yamada A, Aoki Y, Kure S, Matsubara Y | title = Association between nonsyndromic cleft lip with or without cleft palate and the glutamic acid decarboxylase 67 gene in the Japanese population | journal = American Journal of Medical Genetics. Part A | volume = 127A | issue = 1 | pages = 11–16 | date = May 2004 | pmid = 15103710 | doi = 10.1002/ajmg.a.20649 | s2cid = 30016360 }}
</ref> One study found an association between mutations in the [[HYAL2]] gene and cleft lip and cleft palate formation.<ref>{{Cite news|url=http://www.medicalnewstoday.com/articles/315211.php|title=Scientists find genetic mutation that causes cleft lip and palate, heart defects| vauthors = Sandoiu A |date=January 17, 2017|newspaper=Medical News Today|language=en|access-date=January 31, 2017|url-status=live|archive-url=https://web.archive.org/web/20170129210707/http://www.medicalnewstoday.com/articles/315211.php|archive-date=January 29, 2017}}</ref>

====Syndromes====
* The [[Van der Woude syndrome]] is caused by a specific variation in the gene ''[[IRF6]]'' that increases the occurrence of these deformities threefold.<ref>{{cite journal | vauthors = Dixon MJ, Marazita ML, Beaty TH, Murray JC | title = Cleft lip and palate: understanding genetic and environmental influences | journal = Nature Reviews. Genetics | volume = 12 | issue = 3 | pages = 167–178 | date = March 2011 | pmid = 21331089 | pmc = 3086810 | doi = 10.1038/nrg2933 }}</ref><ref>{{cite journal | vauthors = Zucchero TM, Cooper ME, Maher BS, Daack-Hirsch S, Nepomuceno B, Ribeiro L, Caprau D, Christensen K, Suzuki Y, Machida J, Natsume N, Yoshiura K, Vieira AR, Orioli IM, Castilla EE, Moreno L, Arcos-Burgos M, Lidral AC, Field LL, Liu YE, Ray A, Goldstein TH, Schultz RE, Shi M, Johnson MK, Kondo S, Schutte BC, Marazita ML, Murray JC | title = Interferon regulatory factor 6 (IRF6) gene variants and the risk of isolated cleft lip or palate | journal = The New England Journal of Medicine | volume = 351 | issue = 8 | pages = 769–780 | date = August 2004 | pmid = 15317890 | doi = 10.1056/NEJMoa032909 | s2cid = 3324418 }}</ref><ref>{{cite news |url=http://news.bbc.co.uk/1/hi/health/3577784.stm |title=Cleft palate genetic clue found |access-date=July 1, 2007 |work=BBC News |date=August 30, 2004 |url-status=live |archive-url=https://web.archive.org/web/20070208233204/http://news.bbc.co.uk/1/hi/health/3577784.stm |archive-date=February 8, 2007 }}</ref> Mutations in interferon regulatory factor 6 (IRF6) that cause cleft lip palate are also implicated in neural tube defects such as spina bifida.<ref>{{cite journal | vauthors = Kousa YA, Zhu H, Fakhouri WD, Lei Y, Kinoshita A, Roushangar RR, Patel NK, Agopian AJ, Yang W, Leslie EJ, Busch TD, Mansour TA, Li X, Smith AL, Li EB, Sharma DB, Williams TJ, Chai Y, Amendt BA, Liao EC, Mitchell LE, Bassuk AG, Gregory S, Ashley-Koch A, Shaw GM, Finnell RH, Schutte BC | title = The TFAP2A-IRF6-GRHL3 genetic pathway is conserved in neurulation | journal = Human Molecular Genetics | volume = 28 | issue = 10 | pages = 1726–1737 | date = May 2019 | pmid = 30689861 | pmc = 6494790 | doi = 10.1093/hmg/ddz010 }}</ref>
* Another syndrome, Siderius [[X-linked intellectual disability]], is caused by mutations in the ''[[PHF8]]'' gene ({{OMIM|300263||shortlink}}); in addition to cleft lip or palate, symptoms include facial dysmorphism and mild intellectual disability.<ref>{{cite journal | vauthors = Siderius LE, Hamel BC, van Bokhoven H, de Jager F, van den Helm B, Kremer H, Heineman-de Boer JA, Ropers HH, Mariman EC | title = X-linked mental retardation associated with cleft lip/palate maps to Xp11.3-q21.3 | journal = American Journal of Medical Genetics | volume = 85 | issue = 3 | pages = 216–220 | date = July 1999 | pmid = 10398231 | doi = 10.1002/(SICI)1096-8628(19990730)85:3<216::AID-AJMG6>3.0.CO;2-X | doi-access = free }}</ref>

In some cases, cleft palate is caused by syndromes that also cause other problems:
* [[Stickler syndrome]] can cause cleft lip and palate, joint pain, and [[myopia]].<ref>{{cite journal | vauthors = Kronwith SD, Quinn G, McDonald DM, Cardonick E, Onyx P, LaRossa D, Borns P, Stambolian DE, Zackai EH | title = Stickler's syndrome in the Cleft Palate Clinic | journal = Journal of Pediatric Ophthalmology and Strabismus | volume = 27 | issue = 5 | pages = 265–267 | year = 1990 | pmid = 2246742 | doi = 10.3928/0191-3913-19900901-12 }}</ref><ref>{{cite journal | vauthors = Mrugacz M, Sredzińska-Kita D, Bakunowicz-Lazarczyk A, Piszcz M | title = [High myopia as a pathognomonic sign in Stickler's syndrome] | language = pl | journal = Klinika Oczna | volume = 107 | issue = 4-6 | pages = 369–371 | year = 2005 | pmid = 16118961 }}</ref>
* [[Loeys–Dietz syndrome]] can cause cleft palate or [[bifid uvula]], [[hypertelorism]], and [[aortic aneurysm]].<ref>{{cite journal | vauthors = Sousa SB, Lambot-Juhan K, Rio M, Baujat G, Topouchian V, Hanna N, Le Merrer M, Brunelle F, Munnich A, Boileau C, Cormier-Daire V | title = Expanding the skeletal phenotype of Loeys-Dietz syndrome | journal = American Journal of Medical Genetics. Part A | volume = 155A | issue = 5 | pages = 1178–1183 | date = May 2011 | pmid = 21484991 | doi = 10.1002/ajmg.a.33813 | s2cid = 27999412 }}</ref>
* [[Hardikar syndrome]] can cause cleft lip and palate, [[Hydronephrosis]], [[Intestinal obstruction]] and other symptoms.<ref>[http://www.wrongdiagnosis.com/h/hardikar_syndrome/symptoms.htm#symptom_list Hardikar syndrome symptoms]</ref>
* Cleft lip/palate may be present in many different chromosome disorders including [[Patau syndrome]] (trisomy 13).
* [[Malpuech facial clefting syndrome]]
* [[Hearing loss with craniofacial syndromes]]
* [[Popliteal pterygium syndrome]]
* [[Cornelia de Lange syndrome]]
* [[Treacher Collins syndrome]]
* [[Pierre Robin sequence|Pierre Robin syndrome]]<ref>{{Citation| vauthors = Wall J, Albanese CT |title=Pediatric Surgery|date=2015|url=http://accessmedicine.mhmedical.com/content.aspx?aid=1105497830|work=CURRENT Diagnosis & Treatment: Surgery| veditors = Doherty GM |edition=14th|publisher=McGraw-Hill Education|access-date=August 6, 2019}}</ref><ref name = "Meeks_2018" />

====Specific genes====
{| class="wikitable" style = "float: right; margin-left:15px; text-align:center"
|-
! Type
! [[OMIM]]
! Gene
! Locus
|-
| OFC1
| {{OMIM|119530||none}}
| ?
| 6p24
|-
| OFC2
| {{OMIM|602966||none}}
| ?
| 2p13
|-
| OFC3
| {{OMIM|600757||none}}
| ?
| 19q13
|-
| OFC4
| {{OMIM|608371||none}}
| ?
| 4q
|-
| OFC5
| {{OMIM|608874||none}}
| ''[[MSX1]]''
| 4p16.1
|-
| OFC6
| {{OMIM|608864||none}}
| ?
| 1q
|-
| OFC7
| {{OMIM|600644)||none}}
| ''[[PVRL1]]''
| 11q
|-
| OFC8
| {{OMIM|129400||none}}
| ''[[TP63]]''
| 3q27
|-
| OFC9
| {{OMIM|610361||none}}
| ?
| 13q33.1-q34
|-
| OFC10
| {{OMIM|601912||none}}
| ''[[SUMO1]]''
| 2q32.2-q33
|-
| OFC11
| {{OMIM|600625||none}}
| ''[[BMP4]]''
| 14q22
|-
| OFC12
| {{OMIM|612858||none}}
| ?
| 8q24.3
|}

Many genes associated with syndromic cases of cleft lip/palate (see above) have been identified to contribute to the incidence of isolated cases of cleft lip/palate. This includes in particular sequence variants in the genes ''[[IRF6]]'', ''[[PVRL1]]'' and ''[[MSX1]]''.<ref name="pmid14756664">{{cite journal | vauthors = Cox TC | title = Taking it to the max: the genetic and developmental mechanisms coordinating midfacial morphogenesis and dysmorphology | journal = Clinical Genetics | volume = 65 | issue = 3 | pages = 163–176 | date = March 2004 | pmid = 14756664 | doi = 10.1111/j.0009-9163.2004.00225.x | s2cid = 22472334 }}</ref> The understanding of the genetic complexities involved in the [[morphogenesis]] of the midface, including molecular and cellular processes, has been greatly aided by research on animal models, including of the genes ''[[BMP4]]'', ''SHH'', ''SHOX2'', ''[[FGF10]]'' and ''[[MSX1]]''.<ref name="pmid14756664" />