An insight into genetics of non-syndromic cleft palate


1 Medical Genetics Laboratory, Alzahra University Hospital; Pediatric Inherited Disease Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Genetics and Molecular Biology, Medical School, Isfahan University of Medical Sciences, Isfahan, Iran

3 Pediatric Surgery Department, Emam Hossein Hospital, Isfahan University of Medical Sciences, Isfahan, Iran

4 Medical Genetics Laboratory, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran


Our proband is a 29-year-old man, who is affected with soft cleft palate and hypernasality. A study of about six generations of this family pedigree shows that cleft palate has repeatedly occurred in males, with probably a X-linked recessive pattern of inheritance. Interestingly, the sister of the proband is affected with hypernasality and she has an affected son. This is the first report of X-linked inheritance pattern of cleft palate in Iran.


1. Moore G, Jvens A, Chambers J, Bjornsson A, Arnason A, Jensson O, et al. The application of molecular genetics to detection of craniofacial abnormality. Development 1988;103 Suppl:233-9.  Back to cited text no. 1
2. Bush JO, Lan Y, Maltby KM, Jiang R. Isolation and developmental expression analysis of Tbx22, the mouse homolog of the human X-linked cleft palate gene. Dev Dyn 2002;225:322-6.  Back to cited text no. 2
3. Cobourne MT. The complex genetics of cleft lip and palate. Eur J Orthod 2004;26:7-16.  Back to cited text no. 3
4. Fletcher SG. Contingencies for bio-electronic modification of nasality. J Speech Hear Disord 1972;37:329-46.  Back to cited text no. 4
5. Weiss CE. The speech pathologist's role in dealing with obturator-wearing school children. J Speech Hear Disord 1974;39:155-62.  Back to cited text no. 5
6. Davari HA, Zahedi M, Derakhshandeh F. The Prevalence of Hypernasality after Primary Cleft Palate Surgery in Children. Journal of Isfahan Medical School.2012;30:1-7.  Back to cited text no. 6
7. Stanier P, Moore GE. Genetics of cleft lip and palate: Syndromic genes contribute to the incidence of non-syndromic clefts. Hum Mol Genet 2004;13:73-8.  Back to cited text no. 7
8. Sull JW, Liang KY, Hetmanski JB, Fallin MD, Ingersoll RG, Park JW, et al. Excess maternal transmission of markers in TCOF1 among cleft palate case-parent trios from three populations. Am J Med Genet A 2008;146A:2327-31.  Back to cited text no. 8
9. Gorlin RJ, Baylis AL. Embryologic and genetic aspects of clefting and selected craniofacial anomalies. In: Moller KT, Glaze LE, editors. Cleft lip and palate. Interdisciplinary issues and treatment. Austin, TX: Pro-Ed; 2009. p. 104-14.  Back to cited text no. 9
10. Murthy J, Bhaskar LV. Current concepts in genetics of non-syndromic clefts. Indian J Plast Surg. 2009;42:68-81.  Back to cited text no. 10
11. Saikrishna L, Bhaskar LV, Rajasekhar M. Molecular genetics of non-syndromic clefts revisited. Int J Genet 2011;3:23-34.  Back to cited text no. 11
12. Rushton AR. Sex-linked inheritance of cleft palate. Hum Genet 1979;48:179-81.  Back to cited text no. 12
13. Bjornsson A, Arnason A, Tippet P. X-linked cleft palate and ankyloglossia in an Icelandic family. Cleft Palate J 1989;26:1-8.  Back to cited text no. 13
14. Rollnick BR, Kaye CI. Mendelian inheritance of isolated nonsyndromic cleft palate. Am J Med Genet 1986;24:465-73.  Back to cited text no. 14
15. Lowry RB. Sex linked cleft palate in a British Columbian Indian family. Pediatrics 1970;46:123-8.  Back to cited text no. 15
16. Bixler D. Letter to the editor: X-linked cleft palate. Am J Med Genet 1987;26:503-5.  Back to cited text no. 16
17. Hall BD. Letter to the editor: A further X-linked isolated nonsyndromic cleft palate family with a non expressing obligate affected male. Am J Med Genet 1987;26:239-40.  Back to cited text no. 17
18. Moore GE, Ivens A, Chambers J, Farral M, Williamson R, Bjorsson A, et al. Linkage of an X-chromosome cleft palate gene. Nature 1987;326:91-2.  Back to cited text no. 18
19. Gorski SM, Adams KJ, Birch PH, Chodirker BN, Greenberg CR, Goodfellow PJ. Linkage analyses of X-linked cleft palate and ankyloglossia in Manitoba Menonite and British Columbia Native kindreds. Hum Genet 1994;94:141-8.  Back to cited text no. 19
20. Braybrook C, Warry G, Howell G, Mandryko V, Arnason A, Bjornsson A, et al. Physical and transcriptional mapping of the X-linked cleft palate and ankyloglossia (CPX) critical region. Hum Genet 2001b;108:537-45.  Back to cited text no. 20
21. Marçano AC, Doudney K, Braybrook C, Squires R, Patton MA, Lees MM, et al. TBX22 mutations are a frequent cause of cleft palate. J Med Genet 2004;41:68-74.  Back to cited text no. 21
22. Forbes SA, Brennan L, Richardson M, Coffey A, Cole CG, Gregory SG, et al. Refined mapping and YAC contig construction of the X-linked cleft palate and ankyloglossia locus (CPX) including the proximal X-Y homology breakpoint within Xq21.3. Genomics 1996;31:36-43.  Back to cited text no. 22
23. Braybrook C, Warry G, Howell G, Arnason A, Bjornsson A, Moore GE, et al. Identification and characterization of KLHL4, a novel human homologue of the drosophila Kelch gene that maps within the X-linked cleft palate and ankyloglossia (CPX) critical region. Genomics 2001a;72:128-36.  Back to cited text no. 23
24. Gorski SM, Adams KJ, Birch PH, Friedman JM, Goodfellow PJ. The gene responsible for X-linked cleft palate (CPX) in a British Columbia Native Kindred is localized between PGKI and DXYSI. Am J Hum Genet 1992;50:1129-36.  Back to cited text no. 24
25. Puck JM, Willard HF. X Inactivation in Females with X-Linked Disease. N Engl J Med 1998;338:325-8.  Back to cited text no. 25