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Balkan Military Medical Review Oct - Dec 2012; 15(4): 305 -316 Review Article Bilateral Cleft Lip and Palate: An Overview and Discussion of the Literature Dimitrios STAVROPOULOS1, Chryssoula KALAPODA2* Affiliation of the authors: 1. DDS, Dipl.Ortho, PhD, Department of Orthodontics, Naval Hospital of Athens, Greece 2. MD, MSc, Ophthalmologist, Department of Ophthalmology, Attikon General Hospital, Athens, Greece Corresponding author: Lt Commander Dimitrios STAVROPOULOS, (Navy), DDS, Dipl.Ortho, PhD Department of Orthodontics Athens Naval Hospital 70, Deinokratous Street GR 115 25, Athens, GREECE Tel: +30 210 7261297 Fax: +30 210 7294132 E-mail: [email protected] Stavropoulos D. et al: Bilateral Cleft Lip and Palate Abstract The most severe expression of the congenital clefts of the lip and palate (CLP) is the bilateral cleft lip and palate (BCLP), which runs through the lip, the hard, as well as the soft palate. At birth, the maxilla of a child with BCLP is divided into three parts: the premaxilla, which is usually protruded, and the two lateral maxillary segments. It seems that the reasons for the abnormal facial morphology in patients with CLP involve three groups of factors: intrinsic developmental deficiencies, functional distortions affecting the position and growth of both normal and abnormal parts, and iatrogenic (mainly surgical) factors. The iatrogenic factors are implicated as the major source of the midface deficiency reported in patients with CLP. Hypodontia is a very common dental trait in individuals with BCLP, most frequently involving the upper lateral incisors and the second premolars. Posterior and anterior dental crossbites and maxillary incisor rotations are also very common. Although no consensus has been reached on the efficacy and the effectiveness of the different treatment modalities applied, it is evident how tremendously important it becomes to offer centralized treatment to these suffering patients, based on team work of closely cooperating medical and dental specialties. 306 these defects still presents a major clinical problem, but also because they interfere with two of the most important human means of communication: facial expression and speech. The most severe expression of the common orofacial clefts is the bilateral cleft lip and palate (BCLP), which runs through the lip, the hard, as well as the soft palate (Figures 1, 2). It appears when the embryonic medial nasal and maxillary processes fail to unite on both sides. At birth, the maxilla of a child with BCLP is divided into three parts: the premaxilla, which is usually protruded, and the two lateral maxillary segments, which may also deviate in size and position (Figure 2). The nose is wide and flat, due to flared alar bases and short columella [1]. Figure 1: A picture of a neonate with BCLP Keywords: Bilateral cleft lip and palate, treatment, surgery, growth Introduction Congenital clefts of the lip and palate (CLP) constantly raise high research interest not only because the treatment of Figure 2: Maxillary stone model of a neonate with BCLP 307 Hagberg et al. [2] found an incidence of newborns with BCLP of 0.3/1000 live births in the county of Stockholm in Sweden. Bilateral clefts appeared at about 1/3 in frequency comparing to unilateral ones. Generally speaking about all types of CLP, it seems that the highest incidence rate is encountered in Orientals (2-3/1000 live births), then in Caucasians (about 1/1000 live births) and finally in Black population (about 0.4/1000 live births) [1]. Nevertheless, it has to be pointed out that the CLP incidence reported in the literature is strongly influenced by the geographical area where the scientific study is performed and the time spans. For instance, in South European countries the CLP incidence is reported to be around 1/1000 live births, whilst in Northern European countries the incidence is reported to be around 2/1000 live births [3]. It seems that there is a clear gender difference in patients with BCLP. It has been observed that the incidence in males has been double that of the females [4]. In a study by Milerad et al. [5], an association between severe clefts and additional malformations was found. A BCLP was associated with other malformations, such as cardiovascular defects, malformations of the vertebral column and the limbs, in 35% of the cases. The authors concluded that although many associated congenital defects can be detected in a physical examination, the high prevalence of congenital heart disease (16 times more than that reported for the general population) may justify a routine echocardiographic screening in extensive cleft cases. Clinically, when CLP appears with other (usually two or more) malformations in recognizable patterns, it is classified as syndromic. If it appears as an isolated defect, or if syndromes cannot be identified, the term non-syndromic CLP is Balkan Military Medical Review Vol. 15, No 4, Oct –Dec 2012 used [6]. Although CLP can be associated with more than 300 syndromes [7], the majority of these clefts occur as a nonsyndromic form [8]. More than 250 genes have been associated with the development of orofacial clefts in humans [9]. Fraser [10] suggested that the best fitting model of CLP inheritance should be a multifactorial threshold model. Such model describes diseases with complex etiologies involving genetic, epigenetic and environmental components. According to this model, susceptibility to CLP is contributed by multiple factors (genetic, epigenetic and environmental). When these factors accumulate up to a certain threshold value in an individual, cleft occurs. Whether the genetic factors are best explained by a major locus (a unique chromosomal location defining the position of an individual gene or DNA sequence) with reduced penetration [11] or a model of multiple interacting loci [12] is still under scientific debate. Among the environmental factors that predispose for CLP, hypervitaminosis A, folic acid deficiency, smoking habits, maternal periconceptional alcohol consumption and medications such as the anti-acne drug isotretinoin, corticosteroids, and anticonvulsants including phenytoin, valproic acid and oxazolidinediones have been reported in the literature [13-16]. Growth of patients with BCLP Ross [17] postulates that the reasons for the abnormal facial morphology in individuals with CLP involve three groups of factors: (i) intrinsic developmental deficiencies, (ii) functional distortions affecting the position and growth of both normal and abnormal parts and (iii) iatrogenic factors. The only apparent significant intrinsic abnormality is in the maxillary complex with a possibility of a slight mandibular Stavropoulos D. et al: Bilateral Cleft Lip and Palate deficiency. These intrinsic deficiencies are assumed to be invariably mild. Superimposed on the intrinsic factors are functional growth factors, mainly from muscle activity, which cause distortion of both normal and abnormal parts. An example of such growth factors is the premaxillary protrusion and the underdevelopment of the columella seen in patients with BCLP [18]. The protrusion of the premaxilla has been well documented cephalometrically [19] and has been attributed to the absence of the lip restraining effect in unoperated patients with BCLP [20]. When a group of unoperated patients with BCLP was compared with a group of patients with BCLP who had received lip repair only during childhood, the latter group exhibited a significant reduction of the anterior projection of the premaxilla and lingual tipping of the upper incisors [21]. Functional distortions are usually reversible by surgical repair of the lip and palate. The iatrogenic factors (attributed mainly to the surgical management) are, therefore, implicated as the major source of the midface deficiency reported in patients with CLP. The specific maxillofacial growth pattern of the treated cleft face is assumed to be superimposed on the intrinsic deficiency present, as well as on the craniofacial type that is characteristic for the non-cleft population to which the patient with CLP belongs. Will [22] in his review on growth and development in patients with untreated clefts, states that the skeletal and thus, dental width of the unoperated cleft maxilla, is not inherently decreased, but is rather increased. The slightly higher incidence in dental posterior crossbites in unrepaired adult patients might be attributed to some degree of arch collapse brought about by muscle function over the patient’s lifetime. Similarly, although the length of the maxilla seemed to be somewhat shorter in many patients, sagittal 308 growth did not seem to be significantly disturbed. Finally, the mandible was found in many cases retrusive with a quite steep mandibular plane. Friede [23] discusses the growth sites and growth mechanisms at risk in the CLP patient management. The importance of the vomero-premaxillary suture, the intermaxillary suture and the transverse palatine suture for the appositional growth and displacement of the maxillary bony structures is stressed. Strains from lip repair, but most importantly, from the developing scar tissue on the denuded palatal bones, due to the raising of the mucoperiosteal flaps for palatal repair, interfere adversely with the aforementioned sensitive structures. Abnormal tongue posture due to collapsed maxillary segments deteriorates the maxillary dental arch development, both horizontally and vertically [1]. Long et al. [24] depict the main characteristics of treated patients with CLP. They exhibit varying degrees of maxillary sagittal deficiency, which increases with age, although in individuals with BCLP the appearance of the deficiency may be delayed slightly, because of the initial prominence of the premaxilla. Transversally, the maxilla develops varying degrees of medial rotation and collapse of the skeletal and dentoalveolar elements. The predictability of this collapse and its relationship to the development of future posterior crossbite is uncertain. Vertically, the intrinsic mandibular opening rotation may be accentuated by additional primary and secondary surgical procedures. The resultant mandibular retrusion can occasionally mask a maxillary deficiency, at the expense of bimaxillary retrognathic facial profile. Dental development, alignment and occlusion of patients with BCLP 309 Cleft of the primary palate may interfere with normal tooth development, resulting in varied anomalies of the dentition. They can all be related to the initial disturbance and disruption of the embryonic process of dental lamina formation, mainly in the area of failed merging and fusion of the medial nasal, lateral nasal and maxillary processes [1, 25]. Dental traits such as hypodontia, supernumerary teeth, peg-shaped teeth, dental delay, ectopic eruptions of teeth, dental impactions, dental asymmetry and enamel defects and abnormalities occur more frequently in patients with CLP. Hypodontia is very common and most frequently involves the upper lateral incisors and the second premolars in the upper and lower jaws. The tooth most commonly affected is the upper lateral incisor [26]. Its absence appears to be in the range of 10-20% in the primary dentition and 30-50% in the permanent dentition [24]. Bartzela et al. [27] evaluated serial panoramic radiographs of 240 patients with BCLP and found agenesis of at least one tooth (excluding third molars) in 60% of patients. The most frequently missing teeth were upper permanent laterals and upper and lower permanent second premolars. The most common dental agenesis pattern was the simultaneous agenesis of upper permanent lateral incisors and all permanent second premolars. In unoperated patients with BCLP, the maxillary dentoalveolar segments may be rotated medially [20], resulting in arch collapse and dental crossbites in the canine region [28]. Anteroposteriorly, a longer maxillary dental arch has been observed, attributed to the premaxillary anterior projection [29]. In operated patients with BCLP, posterior and anterior crossbites are frequent and become worse in the permanent dentition. Maxillary incisor rotations, lingual dental inclination and Balkan Military Medical Review Vol. 15, No 4, Oct –Dec 2012 anterior crossbites are also common. Maxillary dental midline deviations and asymmetric dental arch form can also be found [30]. Treatment modalities Different treatment protocols are followed in different countries. Optimal habilitation calls for centralized coordinated efforts of a range of clinical specialties, including pediatricians, plastic surgeons, oral and maxillofacial surgeons, otorhinolaryngologists, dentists, orthodo ntists, speech therapists, psychologists. If the CLP patient treatment is centralized, 610% of the patients require orthognathic surgical intervention into the early adult age; otherwise, this percentage rises to 48% [31]. Surgical treatment Early surgical manipulation of the premaxilla Although the protruded premaxilla is of great concern for the parents of a neonate with BCLP and it presents a clinical challenge for proper lip surgery, any premaxillary set-back repositioning has well been abandoned. Damage of the vomero-premaxillary suture results in a severe midfacial retrusion in early adulthood [32]. Nose and lip repair Cleft lip repair is usually carried out when the child is 2-3 months of age [33], one-sided at each time or two-sided at the same time, according to the surgical difficulty. A lip adhesion or lip adaptation is a partial cleft repair that converts a wide complete cleft into an incomplete one, without suturing the lip muscular units [34]. Lip adhesion is usually used as a primary stage for cleft patients with wide Stavropoulos D. et al: Bilateral Cleft Lip and Palate clefts. Definitive lip closure can be done at a later stage. While the short-term effects of lip repair in molding the alveolar segments and narrowing the cleft width are well documented, the possible long-term maxillary growth effects are overshadowed by the subsequent palate repair [35]. According to Mulliken [36], the established principles for successful nose and lip repair in BCLP children are: (i) maintain symmetry, (ii) secure primary muscular union, (iii) design the prolabial flap of correct size and configuration, (iv) form the median tubercle and vermillioncutaneous ridge from lateral labial tissue, (v) construct the nasal tip and columella by anatomic placement of the alar cartilages. Primary nose surgery aims are usually the primary columellar lengthening and nose tip projection gain. However, even with many of surgical protocols available, the primary lip and nose repair show quite often poor aesthetic results, therefore, making plenty of subsequent revision procedures necessary. Palatal repair Posnick [33] states that the main objectives in cleft palatal repair include the achievement of an intact hard and soft palate. The latter should be able to achieve velopharyngeal closure during normal phonation. Berkowitz [37] outlines four common protocols for timing the palatal surgery: early complete palatal repair (3-9 months), delayed complete palatal repair (12-24 months), late complete palatal repair (2-5 years) and two-stage palatal repair with early velar closure (3-9 months) and delayed hard palatal closure (2-9 years). With the assumption that all palatal repairs have the potential to disturb maxillary growth and that the unoperated cleft maxilla exhibits near-normal growth potential, it seems logical to conclude that delaying the procedure until the maxilla has completed more of its growth is a 310 desirable approach. However, with the possibility of worse speech performance in individuals with delayed palatal repair [38], the growth improvements that may be possible can equally be negated in value, because of these concerns [35]. Ross [17] suggests the possibility that the growth effects of a given procedure may be more related to the skill of the surgeon rather than to the particular technique used. The old use of hard tissue for palatal closure has been well discontinued, due to the severe midfacial deficiency it caused [39], therefore only soft tissue closure of the palate with mobilization of mucoperiosteal flaps is currently a standard procedure. Nevertheless, care should be paid not to leave areas of denuded palatal bone, especially adjacent to the alveolar process, as it leads to scar tissue formation with all its adverse contractile effects on maxillary and dentoalveolar growth and development [23]. In an effort to achieve significant reduction in scar tissue formation the attempt to use split-thickness supraperiosteal flaps [40] has been reintroduced. Surgical management Velopharyngeal Insufficiency (VPI) of VPI occurs in 20-30% of children born with palatal clefts after primary palatal repair [41]. VPI results from an inability to accomplish adequate velopharyngeal closure due to a structural or functional deficit in the nasopharynx (i.e., short or poorly mobile velum). The aim of any surgical procedure is to reduce the nasal airflow during speech, which produces phonetic aberrations. The most widely used techniques today are the pharyngeal flap and the pharyngoplasty [42]. The pharyngeal flap remains attached to the posterior pharyngeal wall, while the other end is sutured to various locations in the soft palate to diminish the size of the velopharyngeal port. From the existing 311 Balkan Military Medical Review Vol. 15, No 4, Oct –Dec 2012 literature it is difficult to conclude whether the pharyngeal flap has a mechanical or functional influence on maxillofacial growth [35]. The sphincter pharyngoplasty creates a soft tissue diaphragm, narrowing the nasopharynx and allowing for velopharyngeal closure [43]. Periosteoplasty – gingivoplasty Skoog [44] introduced a surgical approach for primary repair of complete alveolar clefts utilizing periosteal flaps. The rationale for this method was to induce subperiosteal bone formation for creating bony continuity for bridging the alveolar process, even from infancy [45]. However, longitudinal data failed to show satisfactory maxillary growth and ability to produce bone in wide clefts [46]. At the Institute of Reconstructive Plastic Surgery of New York University Medical Center, following a course of maxillary alveolar segment approximation in patients with clefts with the use of intraoral acrylic plates, a gingivoperiosteoplasty (gingivo plasty) is performed [47]. However, no current credible long-term data have been presented so far supporting this technique. Early or primary alveolar bone grafting, introduced in the late 1950s, has now been abandoned in the light of studies showing association with later maxillary retrusion [48]. Late or secondary alveolar bone grafting (i.e., during the mixed dentition) is currently carried out [49]. Midfacial growth disturbance is considered minimal, as by the age of 8 years growth in width and length of the anterior maxilla has almost ceased [50, 51]. Furthermore, the adjacent to the grafted area developing tooth (permanent lateral incisor or canine) can erupt through the graft to its final position in the dental arch. KuijpersJagtman and Long [35] suggest that it may be possible in the future that varied time of secondary bone grafting might be optimal: earlier in patients with healthy lateral incisors or central incisors with marginal bone support requiring an intact alveolar ridge at a younger age, but risking some growth interference if done too early; later in patients with adequate support for cleftadjacent teeth, in which the risk of maxillary growth problems exceeds the benefits of additional surgery at a much younger age. Orthognathic surgery Bone grafting Despite the primary lip and palate repairs, a residual perialveolar oronasal bony defect through the alveolar ridge, anterior part of the hard palate and the floor of the nose will remain to be addressed at a later stage. The best way to bridge this residual defect is by alveolar bone grafting [33], which produces support of cleft adjacent teeth, stabilization of the cleft maxillary segments, support of the alar bases and ability to expand the interpremaxillary suture [24]. In patients with BCLP alveolar bone grafting is often performed in two stages (each cleft side at a time). The primary lip and palate repair performed during infancy and early childhood provides the foundation for normal speech, occlusion, facial appearance and self esteem at the expense of varying maxillary growth restriction due to scar tissue formation. Restriction of maxillary development may continue throughout the growing period and, thus, the situation may worsen with age [1]. The basic orthognathic procedure usually performed for correcting maxillary hypoplasia is a Le Fort I osteotomy [52], sometimes in combination with mandibular set-back [53], applied after completion of facial growth. The use of stabilizing miniplates and autogenous bone grafts to Stavropoulos D. et al: Bilateral Cleft Lip and Palate enhance healing will usually result in acceptable postoperative stability after the maxillary surgery. Nevertheless, in anticipation of a degree of postoperative skeletal relapse, surgical overcorrection of several millimeters is planned, both in the horizontal and transverse dimensions [54]. The application of distraction osteogenesis techniques to cleft-related maxillary deficiencies has broadened treatment versatility and expectations [55]. These are gradual bone lengthening techniques by the employment of distraction devices that separate the bony segments at the osteotomies sites [56, 57]. Orthodontic treatment Presurgical orthopaedics or infant orthopaedics Infant orthopaedics, originated in the 1950’s, is widely used today in many forms, varying in duration and combined with various surgical protocols [23]. This treatment modality aims primarily at active molding and repositioning of the deformed nasal cartilages and alveolar processes, as well as the lengthening of the deficient columella and retraction of the protruded premaxilla of neonates with BCLP into the keystone position between the lateral alveolar segments [47, 58]. The main objective is to reduce the severity of the original cleft deformity, therefore enabling the surgeon to achieve better and more predictable repair of the alveolus, lip and nose. Active or passive molding plates have been used, as well as extraoral traction to set back the premaxilla in patients with BCLP, and nasal stents to form the alar cartilages. This technique has been termed as "nasoalveolar molding" (NAM). A typical NAM appliance consists of an intraoral molding plate with nasal stents to mold the alveolar ridge and nasal cartilage simultaneously [59]. To date, the only prospective randomized clinical trial 312 of infant orthopaedics published, revealed no benefits of this procedure [60]. Deciduous dentition treatment Long et al. [24], in their extensive review paper on orthodontic treatment on children with complete CLP, suggest that most orthodontists either deliver treatment only for severe functional problems or others see no benefit to primary dentition intervention at all. They conclude that the strongest argument against deciduous dentition treatment is that it does not pass the "burden of the patient versus benefit of the treatment" test. Usually, no orthodontic treatment is performed during the deciduous dentition. Mixed dentition treatment The most frequent procedure is the correction of posterior dental crossbites, usually before the alveolar bone grafting of the residual cleft (in case a surgical treatment protocol has been employed from the first years of life of a child with BCLP). The orthodontic appliances of choice are intraoral expansion appliances, such as a quad-helix or removable intraoral plates with expansion screws. Other procedures carried out may include incisor alignment and proclination to remove crowding, rotations and anterior crossbites, and maxillary protraction to reduce maxillary retrusion [1, 23, 24]. Permanent dentition treatment The definitive orthodontic treatment starts after the eruption of the permanent teeth. It involves the application of orthodontic fixed appliances and may be carried out in cooperation with a maxillofacial surgeon, if orthognathic surgery (usually when craniofacial growth has ceased) is part of the overall treatment plan. 313 From the initial statement that an orthodontist, especially in children with BCLP, should not be trapped in ideal goals [1], nowadays with a centralized team care for children with CLP, more and more patients receive normal, everyday orthodontic treatment procedures during the permanent dentition [24]. The use of fixed appliances and the proper cooperation of the patient can usually solve dentoalveolar problems and compensate for adverse dental relationships, if not too severe. In case of missing teeth, decisions have to be made whether a fitting of conventional bridgework or an implantborne prosthesis will be used, or if possible orthodontic space closure will be done. Chetpakdeechit et al. [61] evaluated 35 persons with total BCLP, treated by the Gothenburg CLP team. A good symmetry and a straight midline between jaws were found after treatment for 60% of the young adults. It was more common to have canines positioned in the region of a missing or extracted lateral incisor compared to having the lateral incisor replaced with an implant or other prosthodontic treatment. Finally, when the orthodontic result has been attained, permanent retention is advisable in individuals with BCLP [62]. Conclusion In conclusion, habilitation of patients with BCLP proves to be a very controversial area and demanding process, as seen both from a treatment as well as from a scientific point of view. 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