subject: Cleft Lip and Cleft Palate Gene Targeting [print this page] Cleft Lip and Cleft Palate Gene Targeting
With the recent FDA warning regarding medications linked to cleft palate and cleft lip, interest is once again increasing in the scientific literature. One interesting study is called, "Secondary Bone Grafting of Alveolar Clefts: A Surgical/Orthodontic Treatment Enabling a Non-prosthodontic Rehabilitation in Cleft Lip and Palate Patients" - 1981, Vol. 15, No. 2 , Pages 127-140 by Frank E. byholm, Olav Bergland and Gunvor Semb Here is an excerpt: ""Optimal results were obtained when bone grafting was performed prior to the full eruption of the cleft side canine. In this situation, the known potential of an erupting tooth to induce alveolar bone generation proved to be of great advantage. By deliberately guiding the erupting canine through the grafted area close to the incisor, a nearly normal interalveolar septum was formed, and the gap in the dental arch was closed orthodontically in 23 out of 26 clefts. When fissural teeth were present, they were in most cases integrated in the dental arch. Approximate incisor symmetry could thus be obtained. In the remaining 20 clefts, the ipsilateral canine had not reached its final position at the time of evaluation, and the end results could not be assessed. However, bone formation in the defect was good in 19 of the 20 clefts, and a fully satisfactory result is expected in the majority of these cases. Further advantages were obtained by this procedure: 1) The maxillary segments were stabilized, particularly important in bilateral clefts in which the premaxilla was movable. 2) Oronasal fistulae were effectively closed and mucosal recesses eliminated. 3) The grafted bone provided support for the receded alar base, reducing the nasal asymmetry and improving the facial contour. 4) The postoperative orthodontic treatment could be brought to an end at approximately the same age as for patients with a non-cleft malocclusion. The only significant complication in this series was infection of the grafted area, causing loss of the bone grafts in two cases, and possibly contributing to the failure in some other patients. The experience gained with this treatment permits the conclusion that a full osseous and dental rehabilitation can be achieved in the great majority of patients with cleft lip and palate without any prosthodontic reconstructive work.
One interesting study is called, "Genetics of cleft lip and palate: syndromic genes contribute to the incidence of non-syndromic clefts" - Hum. Mol. Genet. (2004) 13 (suppl 1): R73-R81. Here is an excerpt: "Abstract - Clefts of the lip and/or palate (CL/P) are among the most common birth defects worldwide. The majority are non-syndromic where CL/P occurs in isolation of other phenotypes. Where one or more additional features are involved, clefts are refered to as syndromic. Collectively CL/P has a major clinical impact requiring surgical, dental, orthodontic, speech, hearing and psychological treatments or therapies throughout childhood. The etiology of CL/P is complex and thought to involve both major and minor genetic influences with variable interactions from environmental factors. Using a combination of gene targeting technology and traditional developmental techniques in both mouse and chick, significant progress has been made in the identification of numerous genes and gene pathways critical for craniofacial development. Despite this, it has been a particular source of frustration that mutation screening of specific candidates, association studies and even genomewide scans have largely failed to reveal the molecular basis of human clefting. Nevertheless, some important findings have recently come from studies involving syndromic forms of the disorder. These include several genes which have now been shown to contribute"
Another interesting study is called, "Fetal cleft lip and palate detection by three-dimensional ultrasonography" by W. Lee MD, J. S. Kirk, K. W. Shaheen, R. Romero, A. N. Hodges, C. H. Comstock - Ultrasound in Obstetrics & Gynecology Volume 16, Issue 4, pages 314320, 1 September 2000. Here is an excerpt: "Abstract - Objectives To demonstrate a standardized approach for the evaluation of cleft lip and palate by three-dimensional (3D) ultrasonography. Design - This was a retrospective study of seven fetuses with confirmed facial cleft anomalies. Post-natal findings were compared to a blinded review of 3D volume data from abnormal fetuses with seven other normal fetuses that were matched for gestational age. Upper lip integrity was examined by 3D multiplanar imaging. Sequential axial views were used to evaluate the maxillary tooth-bearing alveolar ridge contour and anterior tooth socket alignment. Alveolar ridge disruption suggested cleft palate. Premaxillary protrusion, either by multiplanar imaging or surface rendering, indicated bilateral cleft lip and palate. Results - Post-natal findings confirmed bilateral cleft lip and palate (four cases), unilateral cleft lip and palate (one case), and unilateral cleft lip (two cases). Multiplanar review identified all three fetuses with unilateral cleft lip, three of four fetuses with bilateral cleft lip, one fetus with unilateral cleft palate, and three of four fetuses with bilateral cleft palate. Surface rendering correctly identified all cleft lips, with the exception of one fetus, who was thought to have a unilateral cleft lip and palate, despite the actual presence of a bilateral lesion. One cleft palate defect was directly visualized by 3D surface rendering. No false-positives occurred.
