Long-term Follow-up of Bilateral Cleft Lip and Palate: Incidence of Speech-Correcting Surgeries and Fistula Formation.

While bilateral cleft lip and palate (BCLP) constitutes a clinical challenge for the whole cleft team, the ideal surgical protocol remains obscure. This study presents the long-term burden of care in terms of secondary surgeries, defined as fistula repair and speech-correcting surgeries (SCS), in a single center. Outcomes of two surgical protocols utilized over the years were also compared.A retrospective single-center analysis of 81 non-syndromic children with complete BCLP born between 1990 and 2010. Two surgical protocols comprising single-stage and two-stage (delayed hard palate closure) procedures were compared. Outcome was analyzed at the time of alveolar bone grafting (ABG) and post-ABG.Altogether 54 children (66.7%) had underwent secondary surgery by the time of bilateral ABG. At this point, 38.3% (n = 31) of patients had received SCS and 49.4% (n = 40) had undergone fistula repair. The corresponding incidences at the end of follow-up were 46.9% (n = 38) and 53.1% (n = 43). No significant difference emerged in SCS incidence between the 2 protocols; however, prior to ABG the single-stage protocol had a significantly lower need for fistula repair. Regarding the location of fistulas, some differences were observed, with the single-stage procedure more associated with anterior fistulas.BCLP has a high surgical burden of care in terms of secondary surgeries, defined as SCS and fistula repair. In our experience, the single-stage protocol, particularly the two-flap technique, offers better results in the management of BCLP than the two-stage approach with a short delay in hard palate closure.

Palatal Re-Repair With Z-Plasty in Treatment of Velopharyngeal Insufficiency of Syndromic and Nonsyndromic Patients With Cleft Palate.

BACKGROUND: Velopharyngeal insufficiency (VPI) often results from palatal shortening or insufficient levator function after cleft palate repair. AIMS: To assess the efficacy of palatal re-repair with Z-plasty in treatment of VPI for patients with isolated cleft palate (ICP). METHODS: This retrospective analysis comprised 130 consecutive patients who had ICP with VPI that required Z-plasty as secondary surgery between 2008 and 2017. Pre- and post-operative evaluation of velopharyngeal function was done perceptually and instrumentally by Nasometer. RESULTS: Median patient age at Z-plasty was 6.8 years (range 3.0-20.1). Of the 130 patients, preoperatively VPI was severe in 73 (56%), mild-to-moderate in 55 (42%), and borderline in 2 (2%). Postoperatively, 105 (81%) of patients achieved adequate (normal or borderline) velopharyngeal competence and 16 (12%) required second operation for residual VPI. The success rate was 84% in nonsyndromic patients, 79% in nonsyndromic Pierre Robin sequence patients, and 58% in syndromic patients. In syndromic children, the speech outcome was significantly worse than in nonsyndromic children (P = 0.014). Complications included wound healing problems in 3 patients (2%), mild infection in 1 patient (1%), postoperative bleeding in 1 (1%), and postoperative fistula in 2 (2%). CONCLUSION: Palatal re-repair with Z-plasty is a safe operation for VPI correction in patients with ICP with a success rate of 81%. In syndromic patients, the procedure did not seem to work as well as in nonsyndromic patients.

Palatal Re-Repair With Double-Opposing Z-Plasty in Treatment of Velopharyngeal Insufficiency of Patients With Unilateral Cleft Lip and Palate.

BACKGROUND: Velopharyngeal insufficiency (VPI) is a common problem after cleft palate repair that is often related to palatal shortening and insufficient levator reconstruction. For VPI correction in our cleft center, palatal re-repair with double-opposing Z-plasty is the standard operation. AIMS: To assess the efficacy of double-opposing Z-plasty in treatment of VPI after primary surgery for unilateral cleft lip and palate (UCLP). METHODS: This retrospective analysis comprised 109 consecutive UCLP patients born between 1997 and 2014 with VPI that required re-operation, and were operated on by 2 highvolume cleft surgeons, followed by perceptual and instrumental (Nasometer) evaluation of velopharyngeal competence (VPC). RESULTS: Preoperatively, VPI was severe in 96% (105 of 109) and mild-to-moderate in 4% (4 of 109). Median age at surgery was 5.6 years (range 2.8-21.9). Postoperatively, 84% of patients achieved adequate VPC: 65% (71 of 109) were competent and 19% (21 of 109) borderline competent. Postoperative adequate VPC was 89% (70 of 79) in nonsyndromic Finnish patients, 50% (4 of 8) in syndromic patients, and 82% (18 of 22) in adoption children. Compared to Finnish nonsyndromic patients, patients with syndrome had more residual VPI (P = 0.003), but no statistically significant difference existed for adoption patients (P = 0.251). Complications of the double-opposing Z-plasty included hemorrhage, postoperative mild airway obstruction, and wound-healing problems, each arising in 2 (1.8%) patients. Fourteen (13%) patients needed a second VPI operation. CONCLUSION: Double-opposing Z-plasty seems to be a good and safe treatment option for VPI in patients with previously repaired UCLP with a success rate of 84%.

Speech of Patients With Unilateral Complete Cleft Lip and Palate: Comparison of Three Different Surgical Protocols for Primary Repair.

BACKGROUND AND AIMS: Between 1997 and 2014, 3 protocols have been used in out cleft unit for primary repair of unilateral cleft lip and palate. During the Scandcleft randomized controlled trial closing the soft palate and lip at 4 months and the hard palate at 12 months (Protocol 1) was compared with closing the entire palate at 12 months (Protocol 2). Protocol 3 comprises closure of the lip and hard palate with a vomer flap at 4 months and the soft palate at 10 months. The purpose of this study was to compare subsequent velopharyngeal competence at age of 3 and 5 years. PATIENTS AND METHODS: The study consisted of 160 non-syndromatic patients with a unilateral cleft lip and palate. Protocol 3 was retrospectively compared with Protocols 1 and 2 within the previously published Scandcleft study. RESULTS: At 3 years of age, normal or borderline competent velopharyngeal function was found in 68% of patients in Protocol 1, 74% of patients in Protocol 2, and 72% of patients in Protocol 3. At 5 years of age, the corresponding figures were 84%, 82%, and 92%. 21% of patients in Protocol 1, 4% in Protocol 2, and 23% in Protocol 3 had palatal reoperations before the age of 5 years. CONCLUSION: No significant differences emerged in velopharyngeal competence at age 3 years between the 3 protocols. Palatal reoperations were performed earlier in patient groups 1 and 3, explaining the difference in the velopharyngeal competence rate at the 5-year time-point.

Scandcleft Project Trial 2-Comparison of Speech Outcome in 1- and 2-Stage Palatal Closure in 5-Year-Olds With UCLP.

OBJECTIVE: To investigate in-depth speech results in the Scandcleft Trial 2 with comparisons between surgical protocols and centers and with benchmarks from peers without cleft palate. DESIGN: A prospective randomized clinical trial. SETTING: Two Swedish and one Finnish Cleft Palate center. PARTICIPANTS: One hundred twelve participants were 5-years-old born with unilateral cleft lip and palate randomized to either lip repair and soft palate closure at 4 months and hard palate closure at 12 months or lip repair at 3 to 4 months (Arm A), or a closure of both the soft and hard palate at 12 months (Arm C). MAIN OUTCOME MEASURES: A composite measure dichotomized into velopharyngeal competency (VPC) or velopharyngeal incompetency (VPI), overall assessment of velopharyngeal function (VPC-Rate), percentage of consonants correct (PCC score), and consonant errors. In addition, number of speech therapy visits, average hearing thresholds, and secondary surgeries were documented to assess burden of treatment. RESULTS: Across the trial, 53.5% demonstrated VPC and 46.5% VPI with no significant differences between arms or centers. In total, 27% reached age-appropriate PCC scores with no statistically significant difference between the arms. The Finnish center had significantly higher PCC scores, the Swedish centers had higher percentages of oral consonant errors. Number of speech therapy visits was significantly higher in the Finnish center. CONCLUSION: At age 5, poor speech outcomes with some differences between participating centers were seen but could not be attributed to surgical protocol. As one center had very few participants, the results from that center should be interpreted with caution.

Incidence of Speech-Correcting Surgery in Children With Isolated Cleft Palate.

OBJECTIVE: Speech-correcting surgeries (pharyngoplasty) are performed to correct velopharyngeal insufficiency (VPI). This study aimed to analyze the need for speech-correcting surgery in children with isolated cleft palate (ICP) and to determine differences among cleft extent, gender, and primary technique used. In addition, we assessed the timing and number of secondary procedures performed and the incidence of operated fistulas. DESIGN: Retrospective medical chart review study from hospital archives and electronic records. PARTICIPANTS: These comprised the 423 consecutive nonsyndromic children (157 males and 266 females) with ICP treated at the Cleft Palate and Craniofacial Center of Helsinki University Hospital during 1990 to 2016. RESULTS: The total incidence of VPI surgery was 33.3% and the fistula repair rate, 7.8%. Children with cleft of both the hard and soft palate (n = 300) had a VPI secondary surgery rate of 37.3% (fistula repair rate 10.7%), whereas children with only cleft of the soft palate (n = 123) had a corresponding rate of 23.6% (fistula repair rate 0.8%). Gender and primary palatoplasty technique were not considered significant factors in need for VPI surgery. The majority of VPI surgeries were performed before school age. One fifth of patients receiving speech-correcting surgery had more than one subsequent procedure. CONCLUSION: The need for speech-correcting surgery and fistula repair was related to the severity of the cleft. Although the majority of the corrective surgeries were done before the age of 7 years, a considerable number were performed at a later stage, necessitating long-term observation.

Dominant mutations in GRHL3 cause Van der Woude Syndrome and disrupt oral periderm development.

Mutations in interferon regulatory factor 6 (IRF6) account for ∼70% of cases of Van der Woude syndrome (VWS), the most common syndromic form of cleft lip and palate. In 8 of 45 VWS-affected families lacking a mutation in IRF6, we found coding mutations in grainyhead-like 3 (GRHL3). According to a zebrafish-based assay, the disease-associated GRHL3 mutations abrogated periderm development and were consistent with a dominant-negative effect, in contrast to haploinsufficiency seen in most VWS cases caused by IRF6 mutations. In mouse, all embryos lacking Grhl3 exhibited abnormal oral periderm and 17% developed a cleft palate. Analysis of the oral phenotype of double heterozygote (Irf6(+/-);Grhl3(+/-)) murine embryos failed to detect epistasis between the two genes, suggesting that they function in separate but convergent pathways during palatogenesis. Taken together, our data demonstrated that mutations in two genes, IRF6 and GRHL3, can lead to nearly identical phenotypes of orofacial cleft. They supported the hypotheses that both genes are essential for the presence of a functional oral periderm and that failure of this process contributes to VWS.

Cleft Lip and/or Palate and Auricular Malformations.

OBJECTIVE: To study the relationship between cleft lip and/or palate and auricular malformations in Finnish patients with cleft. DESIGN: Retrospective analysis of patients with an external ear malformation and either a cleft lip with or without a cleft palate (CL±P) or an isolated cleft palate (CP). SETTING: Tertiary referral clinic. PATIENTS: Review of hospital records of 100 patients from the register of 8200 patients with cleft in the Cleft and Craniofacial Centre at the Helsinki University Central Hospital. MAIN OUTCOME MEASURES: Proportions of variable auricular malformations among CL±P and CP patients. RESULTS: Microtia is the most common auricular malformation among patients with cleft and is almost equally prevalent with both CL±P and CP. The prevalence of microtia increases as the severity of CL±P increases. The combination of microtia and CL±P or CP is frequently found with both oculo-auriculo-vertebral spectrum and Treacher Collins syndrome. CONCLUSIONS: Microtia seems to be the most common auricular malformation among patients with cleft. The prevalence of microtia seems to increase as the severity of CL±P increases, whereas in isolated CP microtia seems to occur independently.

Anterior crossbite, dental arch dimensions, and later need for orthognathic surgery in 6-year-old children with unilateral cleft lip and palate.

Objective : Six-year-old children with unilateral cleft lip and palate were examined to compare the prevalence of anterior crossbite and dental arch dimensions of those who later needed orthognathic surgery with the prevalence of those who did not. Design : Retrospective longitudinal study. Patients : A total of 68 consecutive nonsyndromic patients with unilateral cleft lip and palate (44 boys, 24 girls). Main Outcome Measures : Children with unilateral cleft lip and palate whose palates had been closed in one stage by the Veau-Wardill-Kilner or Cronin-Brauer V-Y pushback techniques were analyzed from dental casts taken at a mean age of 6.1 years (range, 5.7 to 6.8 years) before orthodontic treatment or bone grafting. The need for orthognathic surgery in these patients was determined from hospital records at the mean age of 18.2 years (range, 15.6 to 20.2 years). Student's t test and chi-square test were used in statistical analyses. Results : The prevalence of anterior crossbite was 62% (one or both central incisors in full crossbite). The prevalence was higher (75% versus 53%) in children later needing orthognathic surgery (28 of 68, 41%), but the difference was not significant. Nor were there significant differences in dental arch measurements between children who later needed osteotomies and those who did not or between the two modifications of the primary palatal pushback operations. Conclusions : The prevalence of anterior crossbite and the dental arch dimensions did not differ between 6-year-old children with unilateral cleft lip and palate who later needed orthognathic surgery and those who did not.

Cone beam computed tomography in the assessment of alveolar bone grafting in children with unilateral cleft lip and palate.

OBJECTIVES: To quantify the treatment outcome of secondary alveolar bone grafting (SABG) in individuals with unilateral cleft lip and palate using cone beam computed tomography (CBCT) and to reveal needs for improvement in surgical technique. MATERIAL AND METHODS: CBCT images taken 6 months after SABG of 35 patients were analysed. Vertical and horizontal bone supports of the grafted bone at three levels of the roots of the adjacent teeth were classified, the height of the nasal floor was compared with the unaffected side, and the inter- and intraexaminer reproducibility of these evaluations was assessed. RESULTS: The grafted bone filled the defect in all three vertical measurement levels in 34 per cent. The labiopalatal thickness of the grafted bone was good in at least one-third of the root length in 66 per cent and fair in 34 per cent. Typically, the bone graft was deficient in the apical and palatal direction. Clear asymmetry in the nasal floor was found in 72 per cent. Kappa values indicated excellent agreement for all but one measured parameter. LIMITATIONS: This is a preliminary study involving only a limited number of study subjects. CONCLUSIONS: Our results showed mainly a good or fair treatment outcome. Deficiency of the bone graft was observed mostly in the apical and palatal areas of the defect. Asymmetry of the nasal floor was observed frequently. Careful insertion of the bone graft towards the palatal and apical direction of the cleft is recommended.

Chromosomal abnormalities in Finnish orofacial cleft patients: excess of submucous cleft patients?

OBJECTIVE: The aim was to identify chromosomal regions possibly involved in the development of orofacial clefts and to compare syndromic cleft phenotypes with previous reports. DESIGN: We have retrospectively gathered and analyzed chromosomal aberrations and phenotypes of Finnish cleft patients treated at the Cleft and Craniofacial Centre, Helsinki University Central Hospital. SETTING: The study was carried out at the Cleft and Craniofacial Centre, Helsinki University Central Hospital. PATIENTS: The cleft register contains information on about 7600 Finnish cleft patients. MAIN OUTCOME MEASURES: Identification of patients for further molecular analyses and identification of chromosomal regions associated with orofacial clefting. RESULTS: We identified 37 cleft patients with chromosomal aberrations of putative research interest. CONCLUSIONS: We were able to efficiently select patients for further molecular analyses and identify chromosomal regions that might be associated with orofacial clefting. The percentage of submucous cleft patients among cleft patients with chromosomal aberrations was unexpectedly high.

[Treatment of cleft lip and palate in Finland]. / Huuli- ja suulakihalkioiden hoidon suuntaviivoja.

In Finland about 120 babies are born with cleft lip and palate per year. The largest group is those with isolated cleft palate (60%) and only one fourth have complete cleft lip and palate. The clefts are closed under one year of age. Clefts affect appearance, occlusion and speech and the final outcome can only be assessed at the end of the growth. Centralisation of services and a multidisciplinary team approach has a bigger influence on the final outcome than different treatment protocols, the comparative advantages of which remain unproven. Good documentation is important to assess the level of treatment outcomes.

Embryology and epidemiology of microtia.

The auricle derives from six hillocks arising from the first and second branchial arches. Different hillocks give rise to different parts of the pinna. In the course of embryonic development, the auricle migrates postero-cranially as the mandible enlarges. Auricular malformations, such as microtia, are thought to be related to cell death of the first and second arch derivatives. The prevalence and characteristics of microtia vary in different populations. The prevalence ranges from 0.83 to 17.4 per 10,000. Microtia is more common in males, and right-sided dominance varies from 57 to 67%. The prevalence of aural atresia or stenosis varies from 55 to 93%. Microtia has been associated with numerous risk factors including race and gender. Genetic factors are likely to have an effect at least in some patients with microtia.

The learning curve in microtia surgery.

Reconstruction of the auricle is known to be complex. Our objective was to evaluate the improvement of the outcome of the lobulus-type microtia reconstruction. Patient satisfaction was also evaluated. There are no previous reports of the learning process in this field. Postoperative photographs of 51 microtia reconstructions were assessed and rated by a panel made up of six surgeons. The ratings were gathered to generate learning curves. Twenty-two patients assessed the outlook of their reconstructed ears, and the results were analyzed as a self-assessment group. The reliability of the rating by a panel was tested by intraclass correlations. There is a highly significant increasing trend in learning ( P = 0.000001). This trend is not constantly upward, and the steady state was not reached during the study. In the self-assessment group, females were significantly more critical than males ( P = 0.014). Intraclass correlation for six panel members was 0.90, and the rating was considered reliable. Thus, a long and gentle learning curve does exist in microtia reconstruction. To secure good quality and continuity, centralization of the operations and trainee arrangements are highly advisable. Outcomes of plastic surgery can reliably be rated by an evaluation panel.

[Microtia--not just an ear problem]. / Mikrotia--ei ainoastaan korvaongelma.

Microtia can be defined as a malformation of the auricle with varying severity. In the majority of patients it is combined with atresia or stenosis of the external auditory canal. The prevalence of microtia in Finland is approx. 4 out of 10000. Associated anomalies should be actively seeked and excluded. Approximately 70% of the patients seem to be non-syndromatic. Patients with microtia are known to more than usual have other structural abnormalities. With the exception of the mildest cases, the development of facial structure and dental occlusion should be monitored in all microtia patients, attempting to actively exclude any associated diseases.

Inheritance of microtia in the Finnish population.

OBJECTIVE: To study the inheritance of microtia in the Finnish population, identify families for genetic linkage analyses and compare the phenotype between sporadic and familial patients. METHODS: Retrospective case series and patient questionnaire of 109 microtia patients referred for reconstruction of the earlobe to the Helsinki University Central Hospital during the years 1980-2005. RESULTS: 22 out of the 109 patients had a relative with microtia or preauricular tag. The familial and sporadic patients did not differ in microtia phenotype or sex distribution. Urinary system anomalies were statistically more prevalent in familial patients (p<0.01). The analyses of the birthplace of parents or grandparents of familial or sporadic microtia patients resulted in no evidence for founder effect. CONCLUSIONS: The prevalence of familial microtia/OAVS in the Finnish population is higher than 20%. The sporadic and familial microtia/OAVS patients do not differ in the phenotype or sex distribution. The mode of inheritance seems to be autosomal dominant with incomplete penetrance.

Microtia in Finland: comparison of characteristics in different populations.

OBJECTIVE: To compare the characteristics of microtia in Finland and in other populations. METHODS: Retrospective case series and patient questionnaire of 190 microtia patients referred for reconstruction of the earlobe to the Helsinki University Central Hospital during the years 1980-2005. RESULTS: The prevalence in Finland is 4.34/10,000 and varied in other populations from 0.83 to 17.4/10,000. Microtia is seen more in males (58%), as unilateral (88.4%), right-sided (59.5%) and it is almost always associated with aural atresia or stenosis (93%). There is conductive hearing loss in 96% and sensorineural hearing loss in 8% of the affected ears. 11% of the patients had congenital heart defects, and 5% had anomalies of extremities. CONCLUSIONS: There is variation in the prevalence and characteristics of microtia in different populations.

Craniofacial cephalometric morphology in 6-year-old children with isolated cleft lip, isolated submucous cleft palate, and combined cleft lip and submucous cleft palate.

One hundred and twenty-one cleft children (67 with isolated cleft lip (CL), 32 with isolated submucous cleft palate (SMCP), and 22 with combined cleft lip and submucous cleft palate (CL + SMCP)) were compared retrospectively from lateral cephalograms taken at a mean age of 6.2 years (range 5.5-7.9). None of the children had had their palates repaired or been operated on to treat velopharyngeal insufficiency (VPI). The children with CL + SMCP and CL had similar morphology. They had greater maxillary length, greater maxillary and mandibular prominence, less vertical growth pattern, less deep nasopharyngeal airways, and thinner upper lips than those with isolated SMCP. After 6 years of age one patient with CL + SMCP, none with CL, and 16 with SMCP needed operations for VPI. This small series suggests that children with CL + SMCP and SMCP have different morphology. Although CL + SMCP is a combination of two types of clefts, it seems to be associated with similar morphology to CL.

Scandcleft randomised trials of primary surgery for unilateral cleft lip and palate: 2. Surgical results.

BACKGROUND: Longstanding uncertainty surrounds the selection of surgical protocols for unilateral cleft lip and palate, and randomised trials have only rarely been performed. The Scandcleft Project consists of three trials commenced in 1997 involving ten centres in Denmark, Finland, Norway, Sweden, and the UK. Three groups of centres tested a newly-defined common technique for palatal repair (Arm A) against their local protocols (Arms B, C, D). Arm A was familiar to most of the surgeons in Trial 1, but not to the surgeons in the other Trials. AIM: To evaluate surgical events and complications of the 448 (293 boys, 155 girls) patients with complete unilateral cleft lip and palate (UCLP) enrolled in the three trials. METHOD: The three trials were carried out in parallel in adherence with a fully developed, ethically approved protocol. Operative time, bleeding, complications, and major dehiscence during and after both primary surgeries were recorded by the surgeon. Rates of fistula and surgery for velopharyngeal incompetence (VPI) were assessed until the youngest patient of the study had reached the age of 9 years. Pearson Chi-square statistical analysis was used to compare the outcomes. RESULTS: No significant differences in bleeding, infection, anaesthetic complications or length of hospital stay between the different arms were found for Trial 1. However, in Trials 2 and 3 there were more airway problems in Arm A than with the traditional local protocols (Arms C or D). In Trial 3 fistula and VPI surgery rates were also higher in Arm A. CONCLUSIONS: The results do not provide statistical evidence that any technique is better than others, but indicate that surgery was more problematic for surgeons who were still gaining experience with an unfamiliar surgical protocol. TRIAL REGISTRATION: ISRCTN29932826.

A Scandcleft randomised trials of primary surgery for unilateral cleft lip and palate: 1. Planning and management.

BACKGROUND AND AIMS: Longstanding uncertainty surrounds the selection of surgical protocols for the closure of unilateral cleft lip and palate, and randomised trials have only rarely been performed. This paper is an introduction to three randomised trials of primary surgery for children born with complete unilateral cleft lip and palate (UCLP). It presents the protocol developed for the trials in CONSORT format, and describes the management structure that was developed to achieve the long-term engagement and commitment required to complete the project. METHOD: Ten established national or regional cleft centres participated. Lip and soft palate closure at 3-4 months, and hard palate closure at 12 months served as a common method in each trial. Trial 1 compared this with hard palate closure at 36 months. Trial 2 compared it with lip closure at 3-4 months and hard and soft palate closure at 12 months. Trial 3 compared it with lip and hard palate closure at 3-4 months and soft palate closure at 12 months. The primary outcomes were speech and dentofacial development, with a series of perioperative and longer-term secondary outcomes. RESULTS: Recruitment of 448 infants took place over a 9-year period, with 99.8% subsequent retention at 5 years. CONCLUSION: The series of reports that follow this introductory paper include comparisons at age 5 of surgical outcomes, speech outcomes, measures of dentofacial development and appearance, and parental satisfaction. The outcomes recorded and the numbers analysed for each outcome and time point are described in the series. TRIAL REGISTRATION: ISRCTN29932826.