Orofacial Malformations Research Articles

Assessment the Outcome of Intralesional Bleomycin Injection, dehydrated (95%) Alcohol and Combined of Them in Managements of Orofacial Vascular Malformation

Assessment the Outcome of Intralesional Bleomycin Injection, dehydrated (95%) Alcohol and Combined of Them in Managements of Orofacial Vascular Malformation

Surgical management in a severe OSA patient diagnosed with Stickler syndrome

Stickler syndrome is a genetic disorder of connective tissue. One of the major symptoms associated with this disorder is an oro-facial malformation, which may cause a submucous cleft or a complete cleft of the hard palate. A 32-year-old man diagnosed with Stickler syndrome and a submucosal cleft palate (SMCP) visited our hospital with a chief complaint of excessive daytime sleepiness. The patient was diagnosed with severe obstructive sleep apnea (OSA), and administration of a polysomnography test revealed an apnea-hypopnea index (AHI) of 30.9 events/hour (h). Auto-titrating continuous positive airway pressure was initiated to control the OSA symptoms and subsequently the patient showed some improvement. However, due to continuous velopharyngeal insufficiency symptoms, intravelar veloplasty was performed. Three months after surgery, the AHI had decreased to 12.4 events/h. Recent studies have described a greater risk for OSA in individuals with cleft palate, than in the general population. The present case demonstrates surgical success in a patient with OSA and SMCP, suggesting that palatal surgery may be considered an optional surgical treatment for OSA patients with SMCP.

Impact of Epigenetic Alterations in the Development of Oral Diseases

Epigenetic mechanisms alter gene expression and regulate vital cellular processes that contribute to the onset and progression of major dental diseases. Their reversible character may prove beneficial for therapeutic targeting. This review aims to provide an update on the main epigenetic changes that contribute to the pathogenesis of Oral Squamous Cell Carcinoma (OSCC), pulpitis and periodontitis as well as dental caries and congenital orofacial malformations, in an effort to identify potential therapeutic targets. We undertook a structured search of bibliographic databases (PubMed and MEDLINE) for peer-reviewed epigenetic research studies focused on oral diseases in the last ten years. A qualitative content analysis was performed in screened papers and a critical discussion of main findings is provided. Several epigenetic modifications have been associated with OSCC pathogenesis, including promoter methylation of genes involved in DNA repair, cell cycle regulation and proliferation leading to malignant transformation. Additionally, epigenetic inactivation of tumor suppressor genes, overexpression of histone chaperones and several microRNAs are implicated in OSCC aggressiveness. Changes in the methylation patterns of IFN-γ and trimethylation of histone Η3Κ27 have been detected in pulpitis, along with an aberrant expression of several microRNAs, mainly affecting cytokine production. Chronic periodontal disease has been associated with modifications in the methylation patterns of Toll-Like Receptor 2, Prostaglandin synthase 2, E-cadherin and some inflammatory cytokines, along with the overexpression of miR-146a and miR155. Furthermore, DNA methylation was found to regulate amelogenesis and has been implicated in the pathogenesis of dental caries as well as in several congenital orofacial malformations. Strong evidence indicates that epigenetic changes participate in the pathogenesis of oral diseases and epigenetic targeting may be considered as a complementary therapeutic scheme to the current management of oral health.

Difficult Airway Identification and Management in Patients With Moebius Syndrome

Airway management in patients with Moebius syndrome can be difficult due to the presence of orofacial malformations. This paper aims to present our institution's experience in the evaluation and management of the upper airway in patients with Moebius syndrome METHODOLOGY:: The authors performed a retrospective study including every patient with Moebius syndrome submitted to surgery between 2012 and 2017. Difficult airway was defined as one requiring more than 2 attempts to achieve endotracheal tube placement, a Mallampati score equal or above III, a Cormack score equal or above III, or need of a fiberscope during intubation. Fifty-one patients were included, (39.3% males) requiring 172 procedures. Each patient required an average of 3.37 ± 1.94 anesthetic events. Average Body Mass Index (BMI) was 20.07 ± 6.06, 45.1% were overweight or obese. Four patients (7%) were considered as having a potentially difficult airway. Endotracheal intubation was achieved in all patients; 38 patients were intubated in a single attempt, while the rest were successfully intubated on a second try. Fiberscope was not necessary. Univariate analysis showed that overweight/obese patients were more likely to be considered as having a difficult airway (P = 0.03). Intubation can be difficult in patients with Moebius syndrome, but failure is rare. Overweight or obese patients are at risk of presenting a difficult airway. An extensive preoperative evaluation and adequate communication between the members of the multidisciplinary team in charge of these patients is paramount.

A Five Years Study of Occurrence and Associated Risk Factors for Birth Defects in a Tertiary Care Hospital in Central Nepal

Introduction: Congenital anomalies account for 7.0% of neonatal deaths in Nepal. The present study was carried out to determine the overall rate of congenital malformations, incidence and prevalence in live births, still birth and incidence affecting various organ systems, at Bharatpur Hospital, Nepal.
 Methods: All the intramural deliveries between Jan 2015 to Dec 2019 were included in the study. All the newborns were looked for congenital malformations after birth within seven days. Antenatal ultrasonography findings were noted. 2D echocardiography was also used for all congenital heart diseases, along with routine X-ray chest. A total of 131 babies with congenital problem were studied and the information was recorded in WHO NBBD Proforma. Data were recorded in MS Excel and SPSS 16 version was used for analysis. 
 Results: Out of the total 60160 deliveries, 131 (0.21% of total birth) were with congenital malformations, sex wise distribution was 65 (49.5%) females and 63 (48.7%) males and three (1.8%) were ambiguous. Oro-facial malformation (49, 37.4%) was the commonest form of malformation followed by the musculoskeletal system (31, 23.6 %), centre nervous system (31, 23.6%) and congenital malformations of genital organs (8, 6.0%). 
 Conclusions: The incidence of congenital malformation in this study was 0.21%. Females were more common than males and oro-facial malformation was the commonest type of malformation. Lack of antenatal visit, lack of folic acid during pre-conception period and low socioeconomic status were the commonest risk factors.

Craniofacial, orofacial and dental disorders: the role of the RAS/ERK pathway.

Deviations from the precisely coordinated programme of human head development can lead to craniofacial and orofacial malformations often including a variety of dental abnormalities too. Although the aetiology is still unknown in many cases, during the last decades different intracellular signalling pathways have been genetically linked to specific disorders. Among these pathways, the RAS/extracellular signal-regulated kinase (ERK) signalling cascade is the focus of this review since it encompasses a large group of genes that when mutated cause some of the most common and severe developmental anomalies in humans. We present the components of the RAS/ERK pathway implicated in craniofacial and orodental disorders through a series of human and animal studies. We attempt to unravel the specific molecular targets downstream of ERK that act on particular cell types and regulate key steps in the associated developmental processes. Finally we point to ambiguities in our current knowledge that need to be clarified before RAS/ERK-targeting therapeutic approaches can be implemented.

Copy number variation analysis of twin pairs discordant for cleft lip with or without cleft palate

Non-syndromic cleft lip with or without cleft palate (nsCL/P) is a frequent orofacial malformation. The comparison of concordance rate observed in monozygotic and dizygotic twins supports high level of heritability and a strong genetic component. However, phenotype concordance for orofacial cleft in monozygotic twins is about 50%. The aim of the present investigation was to detect postzygotic events that may account for discordance in monozygotic twins. High-density SNP microarrays hybridization was used to genotype two pairs of monozygotic twins discordant for nsCL/P. Discordant SNP genotypes and copy number variants were analyzed to identify genetic differences responsible of phenotype discrepancy. A number of differences were observed, none involving known nsCL/P candidate genes or genomic regions. Considering the limitation of the study, related to the small sample size and to the large-scale investigation method, the results suggest that the detection of discordant events in other monozygotic twin pairs would be remarkable and warrant further investigations.

BUNDLE OF MEASURES TO SUPPORT INTRAHOSPITAL EXCLUSIVE BREASTFEEDING: EVIDENCE OF SYSTEMATIC REVIEWS.

ABSTRACTObjective: To identify the main recommendations found in systematic reviews regarding exclusive breastfeeding protective factors.Data source: Integrative review based on the guiding question: What evidence is found in literature regarding the protective factors of exclusive breastfeeding during the intrahospital period? A search was conducted in the Cochrane Library, PubMed/MEDLINE and LILACS database using the keyword “Breast Feeding” and the word “Breastfeeding”. Systematic reviews published from 2007 to 2016 that answered the guiding question were included in the study, whereas systematic reviews that analyzed breastfeeding of preterm infants and breastfeeding of children with orofacial malformation were excluded. The sample included eight systematic reviews. Data synthesis: The recommendations related to the protective factors for exclusive in-hospital breastfeeding found in the systematic reviews were: early skin-to-skin contact, rooming-in care, intervention for treating painful nipples during breastfeeding, restriction of infant supplementation, baby-led breastfeeding and educational interventions and support for mothers during hospital stay. The proposed measures included the six practices presented as protective factors. Conclusions: The review enabled the identification of evidence to support the recommended measures from delivery room to hospital discharge, with the aim of encouraging breastfeeding and preventing intrahospital weaning,

Asymmetrically enlarged parietal foramina in a rare case of Goldenhar syndrome with a possible etiopathogenesis.

Goldenhar´s syndrome (GS) also known as oculo-auriculo-vertebral spectrum (OAVS) is a relatively rare condition. GS is of multifactorial etiology that includes environmental and/or genetic factors, in addition to teratogens that disturb the blastogenesis. A 5-year-old girl from Saudi Arabia, was a member of dizygotic twins conceived by assisted reproductive technology (ART), and born with features of GS. She had asymmetrical face, cleft lip and palate, right microphthalmia and microtia. Radiological imaging showed right maxillary and mandibular bone hypoplasia, asymmetrically enlarged parietal foramina, a persistent midline occipital foramen, abnormal bone arising from occipital bone, extending along tentorium cerebelli, and a lipoma at the right tentorium cerebelli. A rudimentary right eye with dermoid cyst and pseudotumor as well as bilateral atresia of external auditory canals were present. Karyotyping was normal. ART and the risk of manipulation of ovum/embryo, was shown to be associated with multiple gestation and an increased risk of major birth defects. Given that our patient was from Eastern-province close to the South of Iraq, where Gulf wars took place and the reported incidence of birth defects, including orofacial malformation, jumped there to about seven-folds, after war, thus, environmental contamination, and the possible teratogenic effect of depleted uranium could not be excluded. In conclusion, our case of GS, disclosed a rare radiological finding in calvarial anatomy, and asserted that, careful clinical evaluation is recommended in cases of GS. ART fertilization risk along with the possible parental environmental exposure were regarded as the potential cooperators of multifactorial etiology in our case.

Evaluation of quality of life in Chilean patients with orthognathic surgery. A cohort study.

Objective: To compare the presurgical and immediate postsurgical quality of life in Chilean patients with orthognathic surgery. Material and Methods: Cohort study. The study included 30 patients (mean age 20.73, 53.33% male) who underwent orthognathic surgery primarily for severe skeletal abnormalities, (17 surgeries, 56.7%) and moderate skeletal abnormalities (12 surgeries, 40%), from three Chilean hospitals between February and June 2016. Patients were asked to answer the World Health Organization quality of life Bref version questionnaire (WHOQOL-BREF) validated in Spanish to measure quality of life (QoL) two weeks before and three months after the surgery. Scores for general QoL and for every domain of QoL were described. Variations in the scores of general QoL were analyzed according to sex and severity of orofacial malformation (mild, moderate or severe) (ttest p <0.05; STATA 10.0). Results: The average score for QoL according to the WHOQOL-BREF scale was 76.43±13.83 before surgery and 90.5±7.18 three months after surgery (p<0.001). Statistically significant differences according to sex and type of orofacial malformation were found (p<0.01). An increase in the score in all the domains of the WHOQOOL-BREF scale was observed. Conclusion: Orthognathic surgery significantly improved QoL scores in Chilean patients according to the WHOQOL-BREF scale.

Moebius syndrome

AbstractMoebius syndrome is a rare congenital disorder involving complete or partial palsy of cranial nerve VII. Other cranial nerves can also be involved along with limb and orofacial malformations. This case report describes and discusses the clinical manifestations and briefly highlights management options for a patient diagnosed with Moebius syndrome.

Correction of Severe Orofacial Malformation with a Combination of Orthodontics and Orthognathic Surgery

Correction of Severe Orofacial Malformation with a Combination of Orthodontics and Orthognathic Surgery

Inhibition of the 3-hydroxy-3-methyl-glutaryl-CoA reductase induces orofacial defects in zebrafish.

Orofacial clefts (OFCs) are common birth defects, which includea range of disorders with a complex etiology affecting formation of craniofacial structures. Some forms of syndromic OFCs are produced by defects in the cholesterol pathway. The principal enzyme of the cholesterol pathway is the 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR). Our aim is to study whether defects of HMGCR function would produce orofacial malformation similar to those found in disorders of cholesterol synthesis. We used zebrafish hmgcrb mutants and HMGCR inhibition assay using atorvastatin during early and late stages of orofacial morphogenesis in zebrafish. To describe craniofacial phenotypes, we stained cartilage and bone and performed in situ hybridization using known craniofacial markers. Also, we visualized neural crest cell migration in a transgenic fish. Our results showed that mutants displayed loss of cartilage and diminished orofacial outgrowth, and in some cases palatal cleft. Late treatments with statin show a similar phenotype. Affected-siblings displayed a moderate phenotype, whereas early-treated embryos had a minor cleft. We found reduced expression of the downstream component of Sonic Hedgehog-signaling gli1 in ventral brain, oral ectoderm, and pharyngeal endoderm in mutants and in late atorvastatin-treated embryos. Our results suggest that HMGCR loss-of-function primarily affects postmigratory cranial neural crest cells through abnormal Sonic Hedgehog signaling, probably induced by reduction in metabolites of the cholesterol pathway. Malformation severity correlates with the grade of HMGCR inhibition, developmental stage of its disruption, and probably with availability of maternal lipids. Together, our results might help to understand the spectrum of orofacial phenotypes found in cholesterol synthesis disorders. Birth Defects Research (Part A) 106:814-830, 2016. © 2016 Wiley Periodicals, Inc.

Swallowing disorders and feeding problems in children and teenagers with cerebral palsy

The present study is designed to investigate the disorders of swallowing and feeding in children and teenagers suffering from cerebral palsy (PC). These disorders can have vital consequences dependent on the pneumonia generated by the false roads. This descriptive study was undertaken on a sample of 65 child and teenager suffering from CP between 2 and 17 years old, in the North-West of Morocco. For that we used the Gross Motor function Classification System, Expanded and Revised (GMFCS- E & R) and a questionnaire of evaluation of the feeding and swallowing. Thus 10,8% of the patients were classified on level I of the GMFCS, 7,7% on the level II, 10,8% on the level III, 33,6% on level IV and 35,6% on the level V. 36,6% of children and 45,8% of teenagers presented frequent bronchial superinfections and that 51,2% of children and 54,2% of teenagers suffer from disorder of the transit, - standard constipation without laxative treatment -. 85,4% of children and 50% of teenagers need a third person to be fed, 70,7% of children and 54,2% of teenagers present false roads while drinking as 31,7% of children have orofacial malformations against 16,7% of teenagers. The retraction of the upper lip was observed at 73,2% of children against 29,2% of teenagers. Labial gripping during the feeding remains impossible at 82,9% from the total of children and 70,8% of the teenagers. Our study with also highlighted the existence of correlations between the GMFCS and which has occurred of false roads while eating and while drinking respectively with r=0,47 and r=0,77. It is necessary to bring to this population of children and teenagers the adapted and effective care, so that they will test a better quality of life.

Phenotypic classification of variability of non-syndromic congenital cleft lip and jaw in Vorderwald × Montbéliarde cattle.

BackgroundNon-syndromic congenital cleft lip and jaw (CLJ) is a condition reported in several cattle breeds, but a detailed classification system does not exist for cattle. The objective of the present study was to describe the phenotypic variability of this orofacial malformation in Vorderwald × Montbéliarde cattle. For this purpose, a classification system of CLJ was developed on examination of five orofacial structures: (1) lips, (2) the processus (proc.) nasalis of the os incisivum, (3) the dental plate with adjacent segments of the hard palate, (4) the facial bones (os incisivum, os maxillare, os nasale and os palatinum) and (5) the mandibles. Each structure was given a score reflecting the degree of the lesion from absent (score 0) to severe.ResultsNine cases were included in the study and they shared absence of the abaxial rostral part of the processus (proc.) nasalis of the os incisivum, partial loss of the rugae palatinae and the dental plate. A sigmoid curvature of the rostral lower jaw as well as a lateral deviation of the face and rostral lower jaw was highly variable in their expression. These deformations were present in eight of nine cases. In addition to the complete CLJ, three animals had an incomplete CLJ on the contralateral site with variable defects of the rostral part of the proc. nasalis of the os incisivum.ConclusionsA complete CLJ is obviously accompanied by a loss of parts of the proc. nasalis of the os incisivum. Extent and localization of the missing parts of the proc. nasalis were similar in all cases. A precise classification of the various CLJ forms is necessary.Electronic supplementary materialThe online version of this article (doi:10.1186/s13028-015-0177-0) contains supplementary material, which is available to authorized users.

P132 – 2903: A newborn with poor feeding and a mask-like face

Case presentation A male newborn, the child of nonconsanguineous parents, presents with poor feeding with difficulty in swallowing, drooling of saliva and clubfeet. He had been delivered by cesarean section 3 days earlier at term with normal body weight, length and head circumference. The boy is non-toxic in appearance and without distress. Both feet appear inverted and adducted with an inability to bring them to midline. The extremities are flexed with normal Moro-, Galant-, walking-, palmar- and plantar reflexes. The face appears symmetric and masklike with mimicking features when crying hardly differing from those at rest. The child is not able to follow laterally an object moving horizontally, no blink is noted when a bright light is shone in his eyes, the sucking reflex is weak and the tongue movements are poor. In retrospect the parents reported the use of misoprostol during the first trimester of pregnancy in an attempt to terminate pregnancy. Discussion Non-traumatic congenital bilateral abducens and facial weakness, the most consistent abnormalities noticed in our newborn are essential clinical features of Mobius syndrome, a condition that is diagnosed clinically. This syndrome results from a developmental anomaly of the rhombencephalon that occurs between the 6th and 12th gestational week. The term Mobius syndrome, which was initially used exclusively to define a congenital bilateral facial weakness associated with restriction of horizontal eye movements, has been subsequently expanded to include palsies of other cranial nerves as well as other malformations, such as cranio-facial and oro-facial anomalies and limb malformations that sometimes concurrently occur. The causes of the syndrome include genetic, ischemic, infectious and above all teratogenic factors such as the ingestion of drugs like cocaine, alcohol, ergotamine derivatives, thalidomide, benzodiazepines, and especially, like in our case, the prostaglandin analogue misoprostol (often used for uterine evacuation in pregnancy).

Epidemiology, Clinical Aspects and Management of Cleft Lip and/or Palate in Burkina Faso: A Humanitarian Pediatric Surgery-Based Study

Background: Cleft lip and/or palate are the most common orofacial malformations. Many studies, especially in developed countries have been conducted on this malformation, but in Burkina Faso, data are scarce and they are not specific to children. The aim of this study was to report the epi- demiological, clinical and therapeutic aspects of cleft lip and/or palate in children in a low-income country. Materials and Method: The authors conducted a retrospective descriptive study based on data of three humanitarian missions of pediatric reconstructive facial surgery which took place in 2007, 2010 and 2014 at Clinique El Fateh-Suka in Ouagadougou, Burkina Faso. All children of 0 - 14 years of age, presenting with cleft lip and/or palate, were included in the study. Results: A total of 185 cases of cleft lip and/or palate were seen during these three humanitarian surgery missions. There were 100 boys and 85 girls. The average age of the children was 2.4 ± 3.2 years (0 - 12 years); there were 8.7% newborns. The commonest type of cleft was cleft lip and palate (49.7%) followed by isolated cleft lip (48.7%) and isolated cleft palate (1.6%). The left side was the most affected (49.2%). In 21.1% of cases, clefts were associated with other congenital malformations. In total, 150 of 185 (81.1%) children underwent surgery and there were no postoperative complica- tions reported. Conclusions: Epidemiological and clinical characteristics of cleft lip and/or palate * Corresponding author.

A narrative review of peri‐operative management of patients with thalassaemia

In thalassaemic patients, multiple organ systems may be affected by the disease, blood transfusion, iron overload and chelating therapy. Patients may develop cardiomyopathy, pulmonary hypertension or heart failure requiring pre-operative echocardiography or cardiac catheterisation. Restrictive lung dysfunction is commonly encountered, especially in patients with splenomegaly. Haemoglobin level should be optimised pre-operatively and maintained at adequate levels with transfusion and blood-saving strategies. Susceptibility to infections should be managed with broad-spectrum antibiotics. Thromboembolic events due to hypercoagulability should be prevented by simple measures, such as graduated compression stockings, intermittent pneumatic compression and early mobilisation, and possibly anticoagulant drugs. When general anaesthesia is administered, the risk of difficult intubation due to oro-facial malformation should be considered. Cardiovascular depression due to negative inotropic and vasodilating effects of general anaesthesia should be minimised. Neuraxial techniques may also be challenging due to spinal skeletal abnormalities and extramedullary haemopoiesis. A multidisciplinary pre-operative approach, clinical optimisation and a carefully planned strategy are mandatory.

Joubert syndrome with cleft palate

Joubert syndrome is a rare autosomal recessive disorder with key finding of cerebellar vermis hypoplasia with a complex brainstem malformation that comprises the molar tooth sign on axial magnetic resonance images. Many congenital malformations such as polydactyly, retinal abnormalities, renal malformations, tongue and other orofacial malformations including midline cleft lip have been reported. In the review of literature we did not come across specific mention of a cleft palate. Until date approximately 200 such cases have been reported in the literature. We present a case of a 7-year-old female patient who has been under treatment since she was 1 year old. She had a microform midline cleft of the lip, a complete cleft of the secondary palate, polydactyly in both hands and feet, along with the features of Joubert syndrome including episodes of apnea and tachypnea, abnormal ocular movements, atonia and the classic molar tooth sign on axial magnetic resonance imaging.

Clinical Presentation of Epignathus Teratoma With Cleft Palate; and Duplication of Cranial Base, Tongue, Mandible, and Pituitary Gland

A 2-day-old girl was diagnosed with an oral epignathus teratoma and an uncommon combination of orofacial malformations including cleft palate; tongue, mandible, cranial base, cervical vertebrae, lower lip, and pituitary gland duplications; and fistula of the glabella and lower lip. Computed tomography revealed that the mass within the nasal cavity had tooth-like calcifications and protruded into the nasopharynx and oral cavity. It was implanted on the anterior wall of the body of the sphenoid bone and was accompanied with mandibular duplication. Magnetic resonance imaging detected duplication of the pituitary gland and confirmed the absence of intracranial communication of the nasopharyngeal mass. The teratoma did not cause respiratory obstruction; however, the patient required continuous nasogastric tube feeding. Usually, an epignathus teratoma is associated with few midline defects and can be corrected with multiple interventions at different time points. The current study describes the surgical procedure comprising excision of the tumor along with reconstructive surgeries of the mandible, tongue, and fistulae undertaken when the infant reached 7 months of age. The cleft palate was repaired at 18 months of age using the Kaplan buccal flap method. Histopathologic examination confirmed a grade 0 teratoma covered with keratinized skin and containing pilosebaceous and sweat glands, adipose tissue, and smooth muscle. The long-term success of this intervention was determined at the follow-up examination conducted at 3 years of age, with no signs of the teratoma recurrence observed.