Cleft Lip and Tooth Formation

Legal firms across the country are investigating cases involving birth defects in children and certain prescription drugs.  One of these birth defects is Cleft Lip, and the amount of research surrounding this issue is pretty vast.  One interesting study is called, "A review of tooth formation in children with cleft lip/palate" by Reijo Ranta D.D.S., Dr. Odont - American Journal of Orthodontics and Dentofacial Orthopedics Volume 90, Issue 1, July 1986, Pages 11-18.  Here is an excerpt: "Abstract - The literature on tooth formation in children with cleft lip and/or palate is reviewed. The main focus of interest is the association of cleft type and dental abnormalities in number, size, shape, timing of formation, and eruption and cause of the abnormalities. The upper lateral incisor is the most susceptible to injury in the area of cleft in both deciduous and permanent dentitions. This tooth is affected in most instances, even in the cases of microforms of the cleft lip. The prevalence of hypodontia increases strongly with the severity of cleft. More teeth are congenitally missing from the upper jaw than from the lower jaw; however, in the permanent dentition both jaws are affected. Very high prevalence of hypodontia are observed in connection with the Van der Woude syndrome associated with cleft and with the Pierre Robin anomaly. Hypodontia is similarly prevalent in subjects with isolated cleft palate with and without a positive family history of clefts. The prevalence of hypodontia varies largely in different populations. Asymmetric formation of the contralateral teeth is a milder form of hypodontia."

Another interesting study is called, "Complete sequencing shows a role for MSX1 in non-syndromic cleft lip and palate" by P A Jezewski, A R Vieira, C Nishimura, B Ludwig, M Johnson, S E O'Brien, S Daack-Hirsch, R E Schultz, A Weber, B Nepomucena, P A Romitti, K Christensen, I M Orioli, E E Castilla, J Machida, N Natsume, J C Murray -
J Med Genet 2003;40:399-407.  Here is an excerpt: "Abstract - MSX1 has been proposed as a gene in which mutations may contribute to non-syndromic forms of cleft lip and/or cleft palate. Support for this comes from human linkage and linkage disequilibrium studies, chromosomal deletions resulting in haploinsufficiency, a large family with a stop codon mutation that includes clefting as a phenotype, and the Msx1 phenotype in a knockout mouse. This report describes a population based scan for mutations encompassing the sense and antisense transcribed sequence of MSX1 (two exons, one intron). We compare the completed genomic sequence of MSX1 to the mouse Msx1 sequence to identify non-coding homology regions, and sequence highly conserved elements. The samples studied were drawn from a panethnic collection including people of European, Asian, and native South American ancestry. The gene was sequenced in 917 people and potentially aetiological mutations were identified in 16. These included missense mutations in conserved amino acids and point mutations in conserved regions not identified in any of 500 controls sequenced. Five different missense mutations in seven unrelated subjects with clefting are described."

Another interesting study is called, "Associated Malformations in Infants With Cleft Lip and Palate: A Prospective, Population-based Study" - PEDIATRICS Vol. 100 No. 2 August 1997, pp. 180-186 by Josef Milerad, Ola Larson, Catharina Hagberg, and Margareta Ideberg - Departments of Pediatrics and  Plastic and Reconstructive Surgery, Karolinska Hospital, Stockholm, Sweden; and the Department of Orthodontics, Faculty of Odontology, Karolinska Institute, Huddinge, Sweden.  Here is an excerpt: "Objective.  Infants with cleft lip and palate may often have other associated congenital defects although the reported incidence and the types of associated malformations vary between different studies. The purpose of this investigation was to assess the prevalence of associated malformations in a geographically defined population. Methods.  The prevalence of associated malformations in infants with clefts were collected prospectively between 1975 to 1992 on all infants born in greater Stockholm, Sweden. The patient records were also compared with data from the National Malformation Registry and other hospital records if any.   Conclusion.   A more extensive cleft seems to be associated with a higher risk for associated malformations. Although many associated congenital defects can be detected at a physical examination, the high prevalence of congenital heart disease (16 times that of general population) may justify a routine echocardiographic screening."

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.