Morphological variability in unrepaired bilateral clefts with and without cleft palate evaluated with geometric morphometrics

In subjects with orofacial clefts, there is an unresolved controversy on the effect of congenital maxillary growth deficiency vs. the effect of surgical intervention on the outcome of treatment. Intrinsic growth impairment in subjects with orofacial clefts can be studied by comparing facial morphology of subjects with untreated cleft and unaffected individuals of the same ethnic background. Bilateral cleft lip and palate is the most severe and least prevalent form of the orofacial cleft. The aim of this study was to compare facial morphology in subjects with unrepaired complete bilateral clefts and unaffected controls using geometric morphometrics. Lateral cephalograms of 39 Indonesian subjects with unrepaired bilateral complete cleft lip and alveolus (mean age: 24 years), or unrepaired bilateral complete cleft lip, alveolus, and palate (mean age: 20.6 years) and 50 age and ethnically matched controls without a cleft (25 males, 25 females, mean age: 21.2 years) were digitized and traced and shape variability was explored using principal component analysis, while differences between groups and genders were evaluated with canonical variate analysis. Individuals with clefts had a more pronounced premaxilla than controls. Principal component analysis showed that facial variation in subjects with clefts occurred in the anteroposterior direction, whereas in controls it was mostly in the vertical direction. Regression analysis with group, sex, and age as covariates and principal components from 1 to 6 as dependent variables demonstrated a very limited effect of the covariates on the facial shape variability (only 11.6% of the variability was explained by the model). Differences between cleft and non-cleft subjects in the direction of facial variability suggest that individuals with bilateral clefts can have an intrinsic growth impairment affecting facial morphology later in life.</p

Early versus late alveolar bone grafting in unilateral cleft lip and palate: Dental arch relationships in pre-adolescent patients.

OBJECTIVE To evaluate the dental arch relationship in preadolescent children with complete unilateral cleft lip and palate after early secondary alveolar bone grafting (E-ABG) by comparing to late bone grafting (L-ABG). MATERIAL AND METHODS Two raters blindly assessed the dental arch relationship with the modified Huddart-Bodenham (HB) Index for 2 groups: E-ABG group (36 children, mean age 9.6 years) and L-ABG group (56 children, mean age 11.1 years). The groups differed with respect to age at which alveolar bone grafting was performed: between 1.4 and 4.1 years (mean 2.2 years, E-ABG group) and after 8 years (L-ABG group). T-test was run to compare scores between 2 groups. Regression analysis was carried out to evaluate gender, age at cleft repair, age at ABG, and age at assessment with the HB index. RESULTS The overall HB scores were -6.77 and -4.25 in the E-ABG and L-ABG groups, respectively (p = 0.025). Regression analysis showed that only the age at cleft repair influenced the HB scores. CONCLUSION ABG carried out between 2 and 4 years of age does not seem to negatively affect the dental arch relationship at the age of 10 years in comparison to L-ABG

The Slavcleft: A three-center study of the outcome of treatment of cleft lip and palate. Part 2: Dental arch relationships.

PURPOSE Our aim was to evaluate the dental arch relationship in a preadolescent Slavic population with unilateral cleft lip and palate (UCLP) by using the Goslon Yardstick. MATERIALS AND METHODS Patients treated in Warsaw, Poland (n = 32), Prague, Czech Republic (n = 33) and Bratislava, Slovakia (n = 30) were included in this retrospective study. Each cleft center used a unique surgical protocol. Three raters scored blindly the dental arch relationship on plaster models. Intra- and inter-rater agreement were assessed with kappa statistics, and differences between the groups were evaluated with one-way analysis of variance. Intra-rater agreement was very good (k > 0.825), while inter-rater agreement was either good or very good (kappa >0.703). RESULTS We found that patients treated in Warsaw showed a more favorable dental arch relationship (Goslon score = 2.58, SD = 0.77) than patients treated in Prague (Goslon score = 3.21, SD = 1.04). Patients treated in Bratislava showed an intermediate Goslon score (3.07; SD = 0.99). CONCLUSION This study showed that the dental arch relationships in patients treated in Warsaw with a one-stage repair were more favorable than in patients treated in Prague and Bratislava with a two-stage protocol and comparable to the best results obtained in the Eurocleft and Americleft studies

The Slav-cleft: A three-center study of the outcome of treatment of cleft lip and palate. Part 1: Craniofacial morphology

Results of a comparison of the outcomes of treatment of cleft lip and palate can be affected by growth characteristics of populations from which subjects with the clefts are derived. Moreover, conventional cephalometric techniques used in cleft studies for analysis of facial morphology provide only a partial description of shape and are confounded by biases regarding the reference structures. In this retrospective comparison, craniofacial morphology of preadolescent patients with unilateral cleft lip and palate treated in Warsaw (n = 35, age = 10.6 years, SD = 1.2), Prague (n = 38, age = 11.6 years, SD = 1.4), and Bratislava (n = 26, age = 10.5 years, SD = 1.6) were evaluated on cephalograms with the cephalometric method used in the Eurocleft study and geometric morphometrics. We found that patients treated in Warsaw showed slightly more favorable outcomes than in Prague and Bratislava. The differences were related primarily to the position of maxillary alveolar process, cranial base, mandibular angle, and soft tissues. Although no association between a component of treatment protocol and the outcome was found, it is possible that organizational factors such as participation of high-volume, experienced surgeons contributed to these results. (C) 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved

Diagnostic criteria in Pai syndrome: results of a case series and a literature review

IF 2.164 (2017)International audiencePai syndrome was originally described as the association of a midline cleft lip, midline facial polyps, and lipoma of the central nervous system. However, only a few patients present with the full triad, and most exhibit a wide spectrum of phenotypic variability. The aim of this study was to phenotypically delineate Pai syndrome and to propose new criteria to facilitate a clinical diagnosis in the future. The study cohort consisted of seven case patients and an additional 60 cases diagnosed with Pai syndrome identified in a literature review. Only 23 of 67 patients presented the full triad as historically described by Pai et al. (1987). A congenital facial midline skin mass was always encountered, particularly affecting the nasal structures (60/67). A midline facial cleft was reported in 45 of 67 patients and a pericallosal lipoma in 42 of 67 patients. The proposed definition of Pai syndrome is the association of (1) a congenital nasal and/or mediofrontal skin mass and/or a mid-anterior alveolar process polyp as a mandatory criterion, and at least one of the following criteria: (2) midline cleft lip and/or midline alveolar cleft, and/or (3) a pericallosal lipoma or interhemispheric lipoma in the case of corpus callosum dysgenesis

Shoulder replacement surgery for osteoarthritis and rotator cuff tear arthropathy

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To determine the benefits and harms of shoulder arthroplasty in adults with osteoarthritis (OA) of the shoulder, including rotator cuff tear arthropathy (RCTA).</p

A mutation screen in patients with Kabuki syndrome

Kabuki syndrome (KS) is one of the classical, clinically well-known multiple anomalies/mental retardation syndromes, mainly characterized by a very distinctive facial appearance in combination with additional clinical signs such as developmental delay, short stature, persistent fingerpads, and urogenital tract anomalies. In our study, we sequenced all 54 coding exons of the recently identified MLL2 gene in 34 patients with Kabuki syndrome. We identified 18 distinct mutations in 19 patients, 11 of 12 tested de novo. Mutations were located all over the gene and included three nonsense mutations, two splice-site mutations, six small deletions or insertions, and seven missense mutations. We compared frequencies of clinical symptoms in MLL2 mutation carriers versus non-carriers. MLL2 mutation carriers significantly more often presented with short stature and renal anomalies (p = 0.026 and 0.031, respectively), and in addition, MLL2 carriers obviously showed more frequently a typical facial gestalt (17/19) compared with non-carriers (9/15), although this result was not statistically significant (p = 0.1). Mutation-negative patients were subsequently tested for mutations in ten functional candidate genes (e.g. MLL, ASC2, ASH2L, and WDR5), but no convincing causative mutations could be found. Our results indicate that MLL2 is the major gene for Kabuki syndrome with a wide spectrum of de novo mutations and strongly suggest further genetic heterogeneity

Mutations In The Interleukin Receptor Il11Ra Cause Autosomal Recessive Crouzon-Like Craniosynostosis

We have characterized a novel autosomal recessive Crouzon-like craniosynostosis syndrome in a 12-affected member family from Antakya, Turkey, the presenting features of which include: multiple suture synostosis, midface hypoplasia, variable degree of exophthalmos, relative prognathism, a beaked nose, and conductive hearing loss. Homozygosity mapping followed by targeted next-generation sequencing identified a c.479+6T>G mutation in the interleukin 11 receptor alpha gene (IL11RA) on chromosome 9p21. This donor splice-site mutation leads to a high percentage of aberrant IL11RA mRNA transcripts in an affected individual and altered mRNA splicing determined by in vitro exon trapping. An extended IL11RA mutation screen was performed in a cohort of 79 patients with an initial clinical diagnosis of Crouzon syndrome, pansynostosis, or unclassified syndromic craniosynostosis. We identified mutations segregating with the disease in five families: a German patient of Turkish origin and a Turkish family with three affected sibs all of whom were homozygous for the previously identified IL11RA c.479+6T>G mutation; a family with pansynostosis with compound heterozygous missense mutations, p.Pro200Thr and p.Arg237Pro; and two further Turkish families with Crouzon-like syndrome carrying the homozygous nonsense mutations p.Tyr232* and p.Arg292*. Using transient coexpression in HEK293T and COS7 cells, we demonstrated dramatically reduced IL11-mediated STAT3 phosphorylation for all mutations. Immunofluorescence analysis of mouse Il11ra demonstrated specific protein expression in cranial mesenchyme which was localized around the coronal suture tips and in the lambdoidal suture. In situ hybridization analysis of adult zebrafish also detected zfil11ra expression in the coronal suture between the overlapping frontal and parietal plates. This study demonstrates that mutations in the IL11RA gene cause an autosomal recessive Crouzon-like craniosynostosis.PubMedScopu