Bilateral Cleft Lip and Palate Causes
Craniofacial defects such as cleft palate and cleft lip are among the most common of all birth defects. A recent warning by the FDA suggests some prescription medications may be linked to these birth defects. The amount of scientific research surround Cleft Lip and Cleft Palate is legion. One interesting study is called, "Maxillary Distraction: Aesthetic and Functional Benefits in Cleft Lip-Palate and Prognathic Patients during Mixed Dentition" by Molina, Fernando M.D.; Monasterio, Fernando Ortiz M.D.; de la Paz Aguilar, María D.D.S.; Barrera, Juan D.D.S. - Plastic & Reconstructive Surgery: April 1998 - Volume 101 - Issue 4 - pp 951-963. Here is an excerpt: "Abstract - In the last few years, distraction techniques have been used successfully to correct the hypoplastic human mandible. In patients with cleft lip and palate, normal growth of the maxilla may be impaired by early cleft repair, and many of them do not respond to orthodontic procedures alone. Maxillary distraction is an alternative technique to correct maxillary hypoplasia during mixed dentition. In the last 3 years, the procedure was performed in 38 patients aged between 6 and 12 years; 18 patients had unilateral cleft lip and palate, 9 patients had bilateral cleft lip and palate, 7 patients had unilateral cleft palate, 2 patients had prognathism, and 2 patients had nasomaxillary dysplasia. Photographs, posteroanterior and lateral cephalograms, and dental models are obtained preoperatively (as well as an orthopantomogram) to locate the tooth buds. A subperiosteal dissection is performed exposing the anterior and lateral aspects of the maxilla, and an incomplete horizontal osteotomy is done above the tooth buds. Using a facial mask and an intraoral fixed appliance system as an anchorage, we initiate on the fifth postoperative day the application of distraction forces. Maxillary advancement between 4 and 12 mm is achieved during 3 to 4 weeks, and a satisfactory class I or II molar relationship is also obtained."
Another interesting study is called, "Anomalies associated with cleft lip, cleft palate, or both" by Robert J. Shprintzen Ph.D., Vicki L. Siegel-Sadewitz, John Amato, Rosalie B. Goldberg, John M. Opitz Editor, James F. Reynolds - American Journal of Medical Genetics - Volume 20, Issue 4, pages 585–595, April 1985. Here is an excerpt: "Abstract - Numerous investigators have reported on a low frequency of other anomalies in patients with cleft lip, cleft palate, or both. The data have been somewhat inconsistent, ranging from a 3% to over 30% frequency of associated malformations. However, a recent study concluded that over half of the children with clefts at a large metropolitan center have associated anomalies. In an effort to elucidate further the genetic and morphologic characteristics of patients with clefts, 1,000 patients with clefts of the lip, palate, or both were examined and reviewed. The results indicate that associated anomalies occur in 63.4% of the sample. Approximately half of the patients with multiple anomalies have recognized syndromes, sequences, or associations, while the other half have physical examination (apparently one-of-a-kind) syndromes. The high frequency of associated anomalies has obvious implications for the genetic counseling offered to all patients at cleft palate and craniofacial centers. The frequency of associated anomalies also raises questions regarding the validity of past genetic research involving populations of subjects with clefts."
Another interesting study is called, "Cleft lip with or without cleft palate: associations with transforming growth factor alpha and retinoic acid receptor loci." By G Chenevix-Trench, K Jones, A C Green, D L Duffy, and N G Martin - Queensland Cancer Fund Research Unit, Queensland Institute of Medical Research, Australia. Am J Hum Genet. 1992 December; 51(6): 1377–1385. Here is an excerpt: "Abstract - The first association study of cleft lip with or without cleft palate (CL/P), with candidate genes, found an association with the transforming growth-factor alpha (TGFA) locus. This finding has since been replicated, in whole or in part, in three independent studies. Here we extend our original analysis of the TGFA TaqI RFLP to two other TGFA RFLPs and seven other RFLPs at five candidate genes in 117 nonsyndromic cases of CL/P and 113 controls. The other candidate genes were the retinoic acid receptor (RARA), the bcl-2 oncogene, and the homeobox genes 2F, 2G, and EN2. Significant associations with the TGFA TaqI and BamHI RFLPs were confirmed, although associations of clefting with previously reported haplotypes did not reach significance. Of particular interest, in view of the known teratogenic role of retinoic acid, was a significant association with the RARA PstI RFLP (P = .016; not corrected for multiple testing). The effect on risk of the A2 allele appears to be additive, and although the A2A2 homozygote only has an odds ratio of about 2 and recurrence risk to first-degree relatives (lambda 1) of 1.06, because it is so common it may account for as much as a third of the attributable risk of clefting. There is no evidence of interaction between the TGFA and RARA polymorphisms on risk, and jointly they appear to account for almost half the attributable risk of clefting."
We all owe a debt of gratitude to these researchers for their fine work and dedication. For more information, please read the studies in their entirety.
Another interesting study is called, "Anomalies associated with cleft lip, cleft palate, or both" by Robert J. Shprintzen Ph.D., Vicki L. Siegel-Sadewitz, John Amato, Rosalie B. Goldberg, John M. Opitz Editor, James F. Reynolds - American Journal of Medical Genetics - Volume 20, Issue 4, pages 585–595, April 1985. Here is an excerpt: "Abstract - Numerous investigators have reported on a low frequency of other anomalies in patients with cleft lip, cleft palate, or both. The data have been somewhat inconsistent, ranging from a 3% to over 30% frequency of associated malformations. However, a recent study concluded that over half of the children with clefts at a large metropolitan center have associated anomalies. In an effort to elucidate further the genetic and morphologic characteristics of patients with clefts, 1,000 patients with clefts of the lip, palate, or both were examined and reviewed. The results indicate that associated anomalies occur in 63.4% of the sample. Approximately half of the patients with multiple anomalies have recognized syndromes, sequences, or associations, while the other half have physical examination (apparently one-of-a-kind) syndromes. The high frequency of associated anomalies has obvious implications for the genetic counseling offered to all patients at cleft palate and craniofacial centers. The frequency of associated anomalies also raises questions regarding the validity of past genetic research involving populations of subjects with clefts."
Another interesting study is called, "Cleft lip with or without cleft palate: associations with transforming growth factor alpha and retinoic acid receptor loci." By G Chenevix-Trench, K Jones, A C Green, D L Duffy, and N G Martin - Queensland Cancer Fund Research Unit, Queensland Institute of Medical Research, Australia. Am J Hum Genet. 1992 December; 51(6): 1377–1385. Here is an excerpt: "Abstract - The first association study of cleft lip with or without cleft palate (CL/P), with candidate genes, found an association with the transforming growth-factor alpha (TGFA) locus. This finding has since been replicated, in whole or in part, in three independent studies. Here we extend our original analysis of the TGFA TaqI RFLP to two other TGFA RFLPs and seven other RFLPs at five candidate genes in 117 nonsyndromic cases of CL/P and 113 controls. The other candidate genes were the retinoic acid receptor (RARA), the bcl-2 oncogene, and the homeobox genes 2F, 2G, and EN2. Significant associations with the TGFA TaqI and BamHI RFLPs were confirmed, although associations of clefting with previously reported haplotypes did not reach significance. Of particular interest, in view of the known teratogenic role of retinoic acid, was a significant association with the RARA PstI RFLP (P = .016; not corrected for multiple testing). The effect on risk of the A2 allele appears to be additive, and although the A2A2 homozygote only has an odds ratio of about 2 and recurrence risk to first-degree relatives (lambda 1) of 1.06, because it is so common it may account for as much as a third of the attributable risk of clefting. There is no evidence of interaction between the TGFA and RARA polymorphisms on risk, and jointly they appear to account for almost half the attributable risk of clefting."
We all owe a debt of gratitude to these researchers for their fine work and dedication. For more information, please read the studies in their entirety.
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