Anna Verdonck

Dental abnormalities, bone graft quality, and periodontal conditions in patients with unilateral cleft lip and palate at different phases of orthodontic treatment.

OBJECTIVES To evaluate the dental and periodontal condition of patients with unilateral cleft lip and palate (UCLP) before orthodontic treatment and evaluate whether the dental and periodontal condition of these patients during and after orthodontic treatment was jeopardized by the duration of the orthodontic and surgical treatment. DESIGN Seventy-five individuals with UCLP (52 males, 23 females), between ages 8 and 20 years, participated in a retrospective study during their final follow-up visit with regard to dental abnormalities, such as hypodontia, external root resorption, crown and root malformation, and supernumerary teeth. Alveolar bone height and periodontal attachment loss on the cleft side were also screened before or after bone grafting and at different stages of orthodontic treatment. RESULTS Hypodontia of the lateral incisor was found in more than 50% of the patients on the cleft side. Second premolars and/or lateral incisors outside the cleft area were missing in 27.2% of the patients. In 32%, malformations of the teeth near the cleft were noticed. In general, the teeth around and in the cleft of the patients showed normal septal bone heights and a healthy periodontium. Sixty of the 75 patients received a bone graft to restore the interrupted alveolar process. In 93.3% of these patients, the cleft was grafted before the eruption of the canine. CONCLUSION The periodontium of the teeth in and around the cleft in patients with UCLP observed during and after orthodontic treatment can cope relatively well with the long orthodontic treatment and combined surgical interventions. The children, who had not yet started treatment, also showed enough bone support and no periodontal problems of the teeth besides the cleft. Early secondary bone grafting seems to give optimal periodontal results.

Prevalence of dentofacial characteristics in a Belgian orthodontic population

Abstract. The aim of this retrospective study was to provide quantitative information on the prevalence of dentofacial characteristics to find correlations between them and to determine the orthodontic treatment need in a Belgian orthodontic population. Data were acquired from 1,477 patients who had initial records made at the Department of Orthodontics, Katholieke Universiteit Leuven, Belgium between February 1983 and June 1997. The prevalence of Angle Class I, Class II div. 1, Class II div. 2 and Class III malocclusions was, respectively, 31%, 52%, 11% and 6%. The male-to-female ratio was 4:6. Spacing and trauma to teeth occurred more in males than in females. The prevalence of the following dentofacial characteristics was significantly different between the Angle classes: segmental crossbite; crossbite of one tooth; facial asymmetry; protral and lateral mandibular shift; horizontal and vertical growth patterns, impacted teeth; traumatised teeth; ectopically erupting canines; age at first records. No significant difference in the prevalence of the Angle classes between the sexes was found. Several clinically relevant correlations were found between the examined dentofacial characteristics. This Belgian orthodontic population from the Leuven region seems to be comparable to other orthodontic populations in Europe.

Treatment of hemifacial microsomia in a growing child: the importance of co-operation between the orthodontist and the maxillofacial surgeon

The treatment of patients with hemifacial microsomia (HM) always requires an interdisciplinary approach including at least maxillofacial surgery and orthodontics. Co-operation not only within the team, but also with the patients and their family is essential in order to achieve the best results. In the case history of the 10-½ year old female patient reported here, three surgical interventions (two with costo-chondral bone grafts) and a 3-year orthodontic treatment have taken place. A harmonious facial and occlusal result was finally reached.

Treatment and standard evaluation using the Peer Assessment Rating index

Abstract The aim of this retrospective study was to determine the outcome of orthodontic treatment carried out on patients by postgraduate students at the Katholieke Universiteit Leuven, Belgium. The treatment outcome of 292 ’final examination’ patients and of 287 ’control’ patients was compared by means of the Peer Assessment Rating (PAR) index. The sample consisted of dental casts representing a wide range of malocclusions at the start of treatment and post-treatment. All patients received non-surgical treatment between 1987 and 1996 by one of 18 different postgraduate students. The data were analysed with a variant of the analysis of covariance. A significantly higher (P<0.001) treatment standard was found for final examination patients compared to the control, indicated by the mean percentage PAR score reduction of 79.1% and 70.7 %, respectively. When the results are expressed in terms of treatment outcome, 44.5% of the examination patients and 44.0% of the controls were allocated to the ’Greatly improved’ group, while 3.1 % of the patients examined and 7.3% of the control patients were classified as ’Worse or no different’.

Comparative effects of neonatal and prepubertal castration on craniofacial growth in rats

The role of endogenous testosterone in the craniofacial growth of the young male rat was investigated. First, the effect of neonatal surgical castration was examined in a randomized, cross-sectional study in which male Wistar rats were allocated to be either castrated or sham-operated 4 h after birth. Then, the effect of prepubertal chemical castration was analysed in a second, randomized longitudinal study in which male Wistar rats were randomly allocated either to a control group or to two experimental groups, one injected with triptorelin at day 25 and the other injected on day 25 and on day 45. Every tenth day between 20 and 70 days of age for the first study, and between 30 and 110 days of age for the second, body length and weight were measured, cephalometric X-rays taken, and blood samples obtained. Neonatal and prepubertal castration resulted in decreased plasma concentrations of testosterone and in delayed growth of somatic and craniofacial components. The initiation, duration and magnitude of the effect was dependent on individual bones (cranial base, skull roof) and on the lower incisor, and related to the testosterone concentrations. These results suggest that testosterone effects participate in the process of normal craniofacial growth, particularly during puberty.

Novel mutations in LRP6 highlight the role of WNT signaling in tooth agenesis.

Purpose:We aimed to identify a novel genetic cause of tooth agenesis (TA) and/or orofacial clefting (OFC) by combining whole-exome sequencing (WES) and targeted resequencing in a large cohort of TA and OFC patients.Methods:WES was performed in two unrelated patients: one with severe TA and OFC and another with severe TA only. After deleterious mutations were identified in a gene encoding low-density lipoprotein receptor-related protein 6 (LRP6), all its exons were resequenced with molecular inversion probes in 67 patients with TA, 1,072 patients with OFC, and 706 controls.Results:We identified a frameshift (c.4594delG, p.Cys1532fs) and a canonical splice-site mutation (c.3398-2A>C, p.?) in LRP6, respectively, in the patient with TA and OFC and in the patient with severe TA only. The targeted resequencing showed significant enrichment of unique LRP6 variants in TA patients but not in nonsyndromic OFC patients. Of the five variants in patients with TA, two affected the canonical splice site and three were missense variants; all variants segregated with the dominant phenotype, and in one case the missense mutation occurred de novo.Conclusion:Mutations in LRP6 cause TA in humans.Genet Med 18 11, 1158–1162.

Pierre Robin sequence: Management of respiratory and feeding complications during the first year of life in a tertiary referral centre.

OBJECTIVES To review early clinical manifestations of Pierre Robin sequence (PRS) and their management during the first year of life in the University Hospitals Leuven. METHODS Retrospective series of 48 patients with PRS born between 2001 and 2011 and treated at a tertiary referral hospital. Review of the current literature about management of respiratory and breathing difficulties in the early life of PRS patients. RESULTS Of our cleft palate patients 15.3% presented with PRS. A syndrome was diagnosed in 14.6%, associated anomalies without a syndromic diagnosis in 56.3% and isolated PRS in 29.2% of the cases. Mortality rate directly related to PRS was 2.1%. Respiratory difficulties were observed in 83.3% and feeding difficulties in 95.6% of the patients. Respiratory problems were addressed in a conservative way in 75%, in a non-surgical invasive way in 42.5% and in a surgical way in 12.5%. A statistically significant relationship between the association of a syndrome or other anomalies, and a higher need for resuscitation and invasive treatment were found (chi-square test, p-values=0.019 and 0.034). Feeding difficulties were managed conservatively in 91.3%, invasively in 80.4% and surgically in 15.2%. CONCLUSIONS PRS is frequently associated with other abnormalities or syndromes. Therefore routine screening for associated anomalies in neonates with PRS is recommendable. Respiratory and feeding complications are highly frequent and possibly severe, particularly in patients with associated anomalies or syndromes, and should be recognized and addressed appropriately in an early stage. There is a potential role for the nasopharyngeal airway in reducing the need for the more traditional surgical interventions for respiratory problems.

Combined Surgical/Orthodontic Treatment and Autotransplantation of a Premolar in a Patient With Unilateral Cleft Lip and Palate

Objective The treatment of a patient with a complete unilateral left cleft lip and palate, agenesis of the left upper second premolar, and a severely malformed left upper lateral incisor is reported. Treatment included placement of an autologous bone graft from the left iliac crest into the alveolar cleft at 8 years of age and transplantation of a lower premolar into the reconstructed alveolar process at 10 years of age. During the succeeding orthodontic treatment, the dental arches were aligned and corrected toward a Class I molar occlusion. One year after the end of treatment, the status of the transplanted premolar was good.

Genotypic and phenotypic variation in six patients with solitary median maxillary central incisor syndrome

Solitary Median Maxillary Central Incisor occurs in 1 of 50,000 live births. It is the mildest manifestation of the holoprosencephaly spectrum and is genetically heterogeneous. Here we report six patients with solitary median maxillary central incisor, and a range of other phenotypic anomalies with different degrees of severity, varying from mild signs of holoprosencephaly to associated intellectual disability, and with different genetic background. Using array comparative genomic hybridization, pathogenic copy number variants were found in three of the six patients. Two patients had a deletion at the 18p11 chromosomal region that includes TGIF1 while the other patient had a deletion at 7q36, including the SHH gene. In one patient, a mutation in SIX3 was detected with exome sequencing, while in the two remaining patients all known holoprosencephaly genes were excluded using multiplex ligation‐dependent probe amplification and sequencing, and remain unsolved. One of the two latter patients had isolated solitary median maxillary central incisor without other visible dentofacial anomalies, while the other had clinical features not part of the known holoprosencephaly spectrum.

Novel IRF6 Mutations Detected in Orofacial Cleft Patients by Targeted Massively Parallel Sequencing

Common variants in interferon regulatory factor 6 (IRF6) have been associated with nonsyndromic cleft lip with or without cleft palate (NSCL/P) as well as with tooth agenesis (TA). These variants contribute a small risk towards the 2 congenital conditions and explain only a small percentage of heritability. On the other hand, many IRF6 mutations are known to be a monogenic cause of disease for syndromic orofacial clefting (OFC). We hypothesize that IRF6 mutations in some rare instances could also cause nonsyndromic OFC. To find novel rare variants in IRF6 responsible for nonsyndromic OFC and TA, we performed targeted multiplex sequencing using molecular inversion probes (MIPs) in 1,072 OFC patients, 67 TA patients, and 706 controls. We identified 3 potentially pathogenic de novo mutations in OFC patients. In addition, 3 rare missense variants were identified, for which pathogenicity could not unequivocally be shown, as all variants were either inherited from an unaffected parent or the parental DNA was not available. Retrospective investigation of the patients with these variants revealed the presence of lip pits in one of the patients with a de novo mutation suggesting a Van der Woude syndrome (VWS) phenotype, whereas, in other patients, no lip pits were identified.