© Borgis - New Medicine 1/2001, s. 27-29
Maria Hortis-Dzierzbicka1, Zofia Dudkiewicz2
Cleft lip/palate - the contemporary view of etiology and treatment
1Department of Pediatric and Adolescent Surgery National Research Institute for Mother and Child, Warsaw, Poland
2Center for Craniofacial Disorders
Head: Associate Professor Zofia Dudkiewicz, M.D.
The authors present the state of the art view on etiology of orofacial clefts and on contemporary tendencies in treatment of cleft lip/palate. While discussing clefting etiology, in recent years special attention has been focused on gene/environment interaction. The paper also extensively presents a team approach to the therapeutic management of cleft lip/palate.
Cleft lip and/or palate is not only among the most common defects encountered in humans, but is without doubt the most controversial anomaly, in view of its complex and diversified etiology and the abundance of concepts, especially surgical, associated chiefly with primary closure of the cleft crevice. These proposals mainly deal with surgical methods and timing of the procedure. A universal tendency nowadays is to accelerate the time of primary operation, which is associated with decreasing surgical trauma. More and more often classic operations after Langenbeck, Veau or Wardill-Killer, combined with extensive delamination of the periosteum, are abandoned in favour of such procedures as non-traumatic employment of vomer flaps in cleft palate surgery. The prevailing opinion in world literature is that primary surgery should be completed before the child is one year old, regardless of the accepted management strategy. One-stage or multi-stage procedures are regarded as equivalent. The early primary surgical management aims at providing conditions as good as possible for speech development, and minimally invasive surgery at the same time prevents the formation of severe iatrogenic maxillo occlusive disturbances that result from tissue scarring in very early childhood. In Poland Dudkiewicz and Kobus (2, 4) are among advocates of the early primary repair, although as for as we know kobus has lately changed his mind (personal communication).
The surgical management of orofacial clefts can be divided into the primary and secondary - reconstructive - treatment. The primary repair consists of closing the cleft crevice and has two basic goals. The former, important from the aesthetic viewpoint, is to restore the normal facial appearance as soon as possible. The latter is to close the pathological communication between the oral and nasal cavities, thus reconstructing the structural basis for the normal functions of sucking, swallowing, masticating, breathing, speaking and hearing. In a child with an orofacial cleft, all these functions are grossly disturbed. The basic factor featuring in most of the above disturbances is the inability of a cleft child to produce negative pressure in the oral cavity when it pathologically communicates with the nasal cavity.
With respect to secondary procedures, which are supplmentary in character and include for example the restoration of the alveolar arch, the predominant opinion holds that a bone graft should be implanted into the alveolar process when the child is 8-11 years old, and the root of the permanent canine tooth is 1/2-2/3 of its normal length. Other corrective procedures that have recently become almost the rule include an early correction of the ala nasi. Such procedures, if performed early, seem to prevent severe deformities of the nose which was previously often condemned to further bone rhinoplasties.
Treatment of an orofacial cleft defect requires a multi-specialist approach and is multi-stage, performed over many years. The defect itself is clearly visible on the face, can often be heard when the patients speaks, and the stigma of cleft lip remains even after... even after the best surgical treatment, the effect of such a deformity on the personal and social life of the patient is enormous. The selection of proper surgical, orthodonic, phoniatric and laryngological management, as well as speech rehabilitation at each stage of treatment is therefore of paramount importance.
In view of the fact that the wait for the outcome of treatment is 12-18 years, there is a need to prepare standardized documentation at defined time intervals and at each therapeutic stage. This facilitates a comparison of late results, thus allowing for determination of the degree of success of any given method based on such a late outcome. Even in centres where approximately 200 new cases of cleft lip/palate are treated annually, in view of the diveristy of the defects at a given time there are around 15-20 children with the same type of clefting. Often these patients have been operated on at different periods and employing diversified methods, which hinders the selection of statistically comparable groups. Therefore, a concept has emerged aimed at reducing the number of cleft li/palate centres and establishing standard, multispecialist records with data collected at the same periods of the child´s life. The concept emphasizes the necessity for comparative studies, not only of an interinstitutional character (these are often impossible to undertake for the above-mentioned reasons), but also carried out in various centres, both national and foreign.
Cleft lip and/or palate accounts for approximately 65% of all congenital developmental craniofacial anomalies, which places the defect in the leading position with respect to incidence among such malformations. The anomaly develops as a consequence of failed midline fusion between the twin facial processes in early fetal life. In the case of the primary palate, i.e. the lip and alveolar process extending to the incisive foramen, such a fusion occurs between 6 and 8 weeks of gestation, while in the case of the secondary palate (the hard and soft palate) it occurs between 8 and 12 weeks of gestation.
Depending on the site where such a failed or incomplete fusion of facial processes occurs, the patient presents with cleft lip, lip and alveolar process unilateral or bilateral cleft lip, alveolar process and palate or isolated cleft palate. The extent of the defect may be diversified, starting from subclinical forms characterized by only a tiny notch in the cleft lip, through to complete clefting. The gravest problems are posed by a submucosal cleft soft palate, as the anomaly is easy to overlook immediately after birth. It is often diagnosed only in later life, when it is manifested as a speech defect characterized by hypernasality.
The incidence of orofacial cleft anomalies is 1.6-2/1000 live births. Approximately 800 affected children are born in Poland every year. There are sex-linked differences in cleft lip/palate incidence. Cleft lip or cleft lip and palate are more predominant in boys, while isolated cleft lip occurs more frequently in girls (3).
As is well known, the etiology especially of isolated non-syndromic forms of cleft lip and palate, is complex. The development of the defect is affected by multiple factors, both genetic and environmental. The degree of contribution of purely genetic factors can usually be established in approximately 20% of cases, while purely environmental factors, such as alcohol, anti-epileptic agents, steroids, maternal metabolic diseases, ionizing radiation, etc. can be related to the defect in approximately 10% of patients.
Numerous cases of cleft lip and/or palate can develop as a consequence of a synergistic action of many mutated genes. Such genes have been detected at various chromosomes, including the transforming growth factor alpha (TGFa), receptor alpha of retinoic acid (RARA) (17q12), MSX1 (4p16,1), BCL3 (19q13) and other genes of 4 and 6p23-24 chromosomes (7).
In recent years, investigations have demonstrated a significant role played in the development of clefting by the interaction between genetic and environmental factors, or, in other words, the role of the genotype in individual susceptibility to environmental factors. The inter-relation between genetic and environmental factors is termed the gene/environment interaction (6) for the sake of simplicity.
As has been exemplified, cigarette smoking seems to act synergistically with a rare polymorphism within the TGFa gene. Children-carriers of this allele whose mothers smoked during pregnancy have a six times greater risk of cleft palate development than children whose mothers did not smoke. An interaction has recently been identified between maternal nutritional status and certain maternal and foetal metabolic genes (e.g. MTHFR, RARA) and genes of the folic acid binding protein. An interaction between genes is also described, the products of which participate in xenobiotic metabolism (genes of P-450 cytochrome) and some environmental teratogens, such as tobacco, alcohol or industrial solvents (6). Due to the employment of association techniques and binding strategy in evaluation of genes-candidates, genes have been identified that may contribute to the development of clefting, such as TGFa, TFGB3 and MSX1 (5).
The concept of a multi-specialist approach to the management of cleft lip and palate is not new, but it has recently been gaining popularity and importance. This is partly due to the „craniofacial lobby ” that has lately emerged, in the United States, Canada and the United Kingdom (1, 8, 10, 11).
In 1991, the American Maternal and Child Health Care Bureau allocated a budget to the American Society of Cleft Palate and Craniofacial Defects for the „development of standards of health care for infants, children and adolescents with craniofacial defects ”. In the same years, a conference attended by 71 participants was held representing various institutions and organizations associated with this problem. The following resolutions were formulated:
1. The above defects should be managed by multi-disciplinary specialist teams.
2. A minimum number of 50 new patients with cleft lip and/or palate annually guarantees a given centre maintenance of the status of a cleft repair team and appropriate clinical experience.
3. The optimum time for the first team evaluation of the patient is when the child is several weeks, and if possible only a few days old.
4. Patients or their caregivers are to be provided with information on recommended therapeutic methods, risk factors, costs and benefits.
5. Efforts aiming at assisting the family in adjusting to the fact of having a child with an orofacial defect should be intensified.
6. It is the obligation of each left repair team to monitor both short-term and long-term results (1).
In his papers published in 1998/99, Strauss (10, 11) presents a comprehensive review of care provided for children with developmental orofacial defects in the United States and Canada.
In March 1996, the British Ministry of Health established a special fund for development of standards of care for children with cleft lip and//or palate. In consequence, the number of centres involved in the management of this defect was reduced from 56 to eight. This happened as a result of the conscientious work of nine experts, who evaluated centers managing patients with craniofacial defects. The majority of 75 surgeons operating on children with these anomalies were found to perform on the average less than one procedure of unilateral cleft lip and palate repair per year. This factor was among the chief determinants responsible for the poor quality of craniofacial health services in the United Kingdom (8).
In 1996, the European Commission initiated a 3-year „Eurocleft Project ”, the aim of which was to improve therapeutic results and care of children with cleft lip and/or palate in Europe, including Central and Eastern European countries. The final report presenting the actual situation in the field of cleft care in Europe and minimal requirements as to medical documentation was distributed to all European governments and appropriate government agencies involved in health care organization. The recommendations of Eurocleft regarding the care of patients with craniofacial defects are as follows:
1. The management of children with cleft lip and/or palate should be implemented by a highly experienced multi-disciplinary team of specialists.
2. Joint decisions as to the therapeutic process should be reached at all stages of therapy.
3. One member of the team should be responsible for treatment coordination.
4. Such co-ordination is important in view of the fact that representatives of various specialties participate in the therapeutic process.
5. It is anticipated that surgeons, orthodontists and logopedists will treat at least 40-50 new patients annually in order to maintain adequate levels of knowledge and experience.
6. Financial resources should be available for professional care of the child in infancy, surgical treatment, dental services, orthodontic services, speech therapy, laryngologic services including periodic assessment of hearing, clinical genetic counseling, psycho-social assistance, and reimbursement of travel costs.
1. ACPCA: Team Standards Committee: Evaluation and treatment parameters in the care of patients with cleft lip/palate or other craniofacial disorders, CP Craniofac J 1993, 30, suppl. 1. 2. Dudkiewicz Z: Rozszczep wargi i podniebienia, w: „Chirurgia Glowy i Szyi ” pod red. L. Krysta, PZWL 1996. 3. Fara M, et al.: Orofacial clefts - a theoretical basis for their prevention and treatment. Acta Universitatis Carolinae, Praha 1988. 4. Kobus K: Nowe koncepcje i metody w leczeniu rozszczepów wargi i podniebienia, Pol Przegl Chir 1992, 64:453-462. 5. Lidrar AC, Romitti PA, Basart AM, et al.: Association of MSX1 and TGFB3 with nonsyndromic clefting in humans. Am J Hum Genet 1998, 63:557-568. 6. Mossey PA: Development of methods to investigate the interaction between nutritional, environmental and genetic factors in early human development. Abstract from the 6thEuropean Craniofacial Congress, Manchester, 15-18 June 1997. 7. Nucklolls GH, Shum L, Slavkin H: Progress toward understanding craniofacial malformations. CP Craniofac J 1999, 36:12-26. 8. Sandy J, et al.: The Clinical Standards Advisory Group (CSAG) Cleft Lip and Palate Study, Br J Orthod 1988, 25:21-30. 9. Shaw GM, et al.: Orofacial clefts, palatal smoking and TGFa, Am J Hum Genet 1996, 58:551-561. 10. Strauss RP: Cleft palate and craniofacial teams in the USA and Canada: A national survey of team organisation and standards of care, CP, Craniofac J 1998, 35:473-480. 11. Strauss RP: The organisation and delivery of craniofacial health services: the state of the art, CP Craniofac J 1999, 36:189-195.