Congenital Craniofacial Abnormalities Research Articles

Incidence and clinical characteristics of congenital nasolacrimal duct obstruction with concurrent craniofacial abnormalities among a population-based cohort

ABSTRACT Purpose Data supporting treatment recommendations for congenital nasolacrimal duct obstruction (CNLDO) in patients with craniofacial abnormalities is scarce. This study reports the incidence, clinical features, and outcomes of patients with concomitant craniofacial abnormalities and CNLDO. Methods This multi-center, retrospective, population-based cohort study included all patients diagnosed with CNLDO before age 6 during a 10-year period in a single US county. Results Of the 17,713 live births during the study period, 1998 infants were diagnosed with CNLDO, among whom 41 (2.05%) had associated congenital craniofacial abnormalities, yielding a birth prevalence of 23.1 (95% CI 16.6–31.4) per 10,000 live births. Craniofacial patients were significantly older at time of diagnosis (6.2 months) compared to uncomplicated CNLDO (3.7 months; p = 0.035). There was no significant difference in mean age at spontaneous CNLDO resolution, but 31.7% of craniofacial patients required probing for CNLDO resolution, compared to 14.5% in the CNLDO group (OR 2.76 [95%CI 1.41–5.39] p = 0.003). All but two patients with craniofacial abnormalities had resolution of symptoms after initial probing. Intraoperative probing findings indicated that 8 of 13 craniofacial patients had complex obstructions. Conclusions The similar age at spontaneous resolution indicates that watchful waiting until approximately one year of age is a reasonable approach even in patients with craniofacial abnormalities, though more of these patients may require surgical intervention.

Characteristic craniofacial defects associated with a novel USP9X truncation mutation

Germline loss-of-function mutations in USP9X have been reported to cause a wide spectrum of congenital anomalies. Here, we report a Japanese girl with a novel heterozygous nonsense mutation in USP9X who exhibited intellectual disability with characteristic craniofacial abnormalities, including hypotelorism, brachycephaly, hypodontia, micrognathia, severe dental crowding, and an isolated submucous cleft palate. Our findings provide further evidence that disruptions in USP9X contribute to a broad range of congenital craniofacial abnormalities.

Comparison of the Outcomes of Surgical Repair of Cleft Palate Performed by Modified Von Langenbeck and Bardach (Two-Flap Palatoplasty) Methods.

Cleft lip and cleft palate are one of the most common congenital craniofacial abnormalities in the skull and face. We aimed to investigate the prevalence of complications after primary cleft palate repair surgery, performed on patients referred to a children's hospital, and to use the information and results obtained from it to reduce the complications and improve the results of these surgeries. In this cross-sectional-analytical study, using a census sampling method, the medical records of 94 consecutive cleft palate patients treated in Abuzar Hospital in Ahvaz, southern Iran, in the years 2019 to 2021 were studied. The rate of postoperative complications during the first week in terms of wound opening and flap necrosis and one month later in terms of fistula formation after surgery were also extracted from the files. Ninety-four patients with congenital cleft palate (57.4% male and 42.6% female) were enrolled. The gap width in all studied patients was 14 ± 5 mm. The frequency of complications of surgical wound opening, flap necrosis, oronasal fistula and hypernasality in von Langenbeck group was 9.5%, 0.15% and 28.1% respectively, and in Bardach group was 9.5 %, 15% and 33.3% respectively. There were no significant differences between the two surgical methods in terms of postoperative complications. Besides, what is important in choosing a surgical method is the patient's clinical condition, the surgeon's experience and skill, and his choice.

Pediatric Insurance Coverage Variation of Orthognathic Surgery and Orthodontic Treatment for Congenital Craniofacial Abnormalities

Introduction: Orthognathic surgery and associated orthodontic treatment are necessary parts of care for children who have congenital craniofacial deformities. Inconsistencies in insurance coverage across the U.S. have led to serious barriers to care for many families. In an effort to describe common patterns of coverage, we report craniofacial coverage criteria for both medical and dental insurances. Methods: In this study, we analyzed medical policies of the top 50 market share insurance providers, as well as all dental policies available in the U.S., for a total of 776 policies. Included in this analysis are Medicaid and Children’s Health Insurance Program (CHIP). Results: A total of 94.1% of both private medical and dental policies provide up-front limited coverage of congenital-related treatments, along with 98.0% of Medicaid plans covering oral surgery for cleft palate. Almost all states (n = 47) offered at least one private medical plan that covered orthognathic surgery for congenital and craniofacial anomalies, while n = 3 states (Colorado, Ohio, West Virginia) did not offer any. Coverage for oral surgery and orthodontic treatment by private dental and standalone dental plans were consistent, with 80.9% (n = 518) plans offering (52 ± 14)% in-network coverage of costs for oral surgery and 55.6% (n = 356) offering a similar (49 ± 12)% out-of-network coverage. Forty-six Medicaid and 44 CHIP programs offered coverage of “oral surgery for cleft palate.” Of these plans, 8.8% (n = 9) covered oral surgery as a medical benefit and 2.9% (n = 3) required that the surgery be “medically necessary.” Fifty Medicaid and 48 CHIP plans offered coverage for orthodontia. Conclusion: Many systemic barriers remain in the way of consistent access to affordable care in the United States. Coverage for patients with congenital anomalies remains highly variable and greater efforts are needed to ensure consistent, comprehensive coverage.

Diagnosis of Treacher-Collins Syndrome: The role of the multidisciplinary team in patient management and family genetic counseling

INTRODUCTION: Although Treacher-Collins syndrome has to be considered a differential diagnosis in congenital craniofacial abnormalities, the clinical diagnosis and research related to it still present a gap, especially in African regions. Thus, this work aims at highlighting this syndrome's clinical features for raising medical awareness. CLINICAL CASE: We reviewed a 1-year-old patient referred to our clinical genetic unit at Rwanda military hospital, Kigali, Rwanda. Physical examinations indicated severe craniofacial abnormalities, including downward-sloping eyes, slight notching of the lower lids, small and underdeveloped eyebrow bones, vision problems, small outer ears, small and underdeveloped cheekbones, and jaw. Within the limits of the techniques used in our laboratory, the cytogenetic analysis revealed a normal karyotype, 46, XY. CONCLUSION: The patient was diagnosed with Treacher-Collins syndrome based on clinical manifestations of craniofacial features. Nevertheless, laboratory tests performed were limited to karyotyping and should not detect any gene defect. Long-term follow-up of the patient and his family was recommended. Further molecular analyses should be performed to identify causing genetic mutation mainly in the TCOF1, POLR1C, or POLR1D genes.

Temporomandibular joint asymmetry in asymptomatic skeletal class I patients

Objectives Analysis of TMJ asymmetry in a sample of asymptomatic skeletal class I patients. Patients and methods This study was performed on one hundred patients requesting CBCT scans. All patients were skeletal class I pattern. They were all free of TMD symptoms, midline deviation of teeth, open bite, cross bite, congenital craniofacial abnormalities or any systemic diseases which may affect joint morphology such as rheumatoid arthritis. TMJ was evaluated through linear and volumetric analysis. Qualitative condyle position was also evaluated. All measures were compared on the right and left sides. Results There was relative asymmetry between right and left sides regarding all measured parameters. Condyle height showed the highest asymmetry, while condyle AP dimension was the least. There was absolute asymmetry between right and left sides regarding all measured parameters. fossa roof thickness showed the highest asymmetry, while condyle ML width was the least. On Correlating the R and L measurements, all correlations were positive with medium strength and were statistically highly significant. The highest correlation was shown in condyle volume while fossa roof thickness showed the least. The distributions of cases according to condyle position were almost statistically significantly different between right and left sides with 49 % percentage of agreement. Conclusion TMJ shows relative and absolute asymmetry in skeletal class I asymptomatic patients.

17 A De novo Recessive Mutation Causative of Mandibulofacial Dysostosis in Hereford Cattle

Abstract In spring 2020, six Hereford calves presented with congenital craniofacial abnormalities attributed to a condition we termed mandibulofacial dysostosis (MD). Pedigree analysis revealed a single common ancestor shared by the sire and dam of each affected calf. We hypothesized that MD in Hereford cattle is attributed to a de novo mutation with an autosomal recessive mode of inheritance. To avoid production of affected calves, the objective of this study was to identify the cause of MD. Whole-genome sequencing (WGS) of 20 animals (3 affected, 7 obligate carriers, 10 related) yielded 143 variants matching the hypothesized mode of inheritance. Genotyping of 2 additional affected calves, 760 Herefords, and evaluation of WGS data from over 2,500 other individuals led to the discovery of a missense mutation (Chr26 g. 14404993 T >C) in CYP26C1 associated with MD. The amino acid change due to the CYP26C1 variant (p. L188P) is located in an α helix of the protein; modeling suggests the substitution breaks the helix. The mutation is predicted to be deleterious (SIFT = 0) and is otherwise conserved across species. In our data, all heterozygotes had at least one pedigree tie to the suspect founder. CYP26C1 plays a vital role in tissue-specific regulation of retinoic acid (RA) during embryonic development. Dysregulation of RA can result in teratogenesis by altering the endothelin-1 signaling pathway affecting the expression of Dlx genes, critical to mandibulofacial development. Further, multiple human conditions with similar pathologic characteristics are attributed to dysfunction of this gene and/or retinoic acid signaling. We conclude that this recessive missense mutation in CYP26C1 impacts the catalytic activity of the encoded enzyme, leading to excess RA and resulting in the MD phenotype. Breeders can now genotype their animals to identify carriers. These data also contribute to expanding the understanding of craniofacial development across species.

Congenital Craniofacial Abnormalities in Olive Ridley Sea Turtle Hatchlings

The Olive Ridley (Lepidochelys olivacea), is the most abundant species of sea turtles in the world, but is still threatened according to the red list of endangered species. Apparently, the Olive Ridley turtle seems more prone to congenital malformations compared to other species of sea turtles. In northwestern Mexico, an incidence of congenital malformations of 2% has been reported for this species, most of which occur in the craniofacial region (49%). The objective of this study was to deduce the etiology of the malformations based on the pattern of the affected structures. During the 2019 nesting season at El Caimanero nesting beach, Sinaloa, Mexico, 11 specimens with external craniofacial malformations and 10 that did not show external malformation were collected. The normal animals hatched, but died from other natural causes within the nests. Specimens were divided between histological analysis or µCT with phosphotungstic acid contrast enhancement. Specimens with malformations consistent with a Holoprosencephaly (HPE) phenotype were detected (Table 1). Analysis PTA staining and µCT showed there was a single external naris. There was variability in the morphology of the nasal passages. Other midline structures were also deficient including absent interorbital septum and small premaxilla. However, two other cardinal signs of severe HPE were not seen. The brain was divided into right and left hemispheres and the eyes were separated. There were additional defects in the mandible affecting mesodermal derivatives of the first arch. The tongue was severely hypoplastic and the musculature in the floor of the oral cavity was deficient. The tracheal opening was also displaced posteriorly in the tongue compared to the usual position in the center of the tongue. The nasal defects may be caused by a hypoplastic frontonasal process which allows merging of the nasal pits. The muscular deficiencies in the tongue are likely due to incomplete formation of lingual swellings in the first pharyngeal arch. Nasal development was normal in the majority of animals and the most common defect was mandibular deviation combined with hypoplasia. The defects observed are consistent with a mild form of HPE but also with ciliopathies that include tongue agenesis. Further histological analysis will be carried out to assess cellular and molecular phenotypes. This work suggest pleotropic environmental effects cause the embryonic defects after the eggs are oviposited in the nest. This turtle species lays eggs with embryos in the gastrula stage of development, reaching pharyngula stage, 3-4 days after laying. Therefore, we postulate an exposure to an environmental teratogen in the first 4 days is responsible for the congenital abnormalities.

Онтологія варіантів будови та вад розвитку черепа. Частина I

Annually severe congenital abnormalities occur in 1 of 33 newborns or about 125.000 live births in the United States and are the leading cause of infant mortality. Craniofacial anomalies account for about one-third of all abnormalities. The prevalence of human congenital malformations is an important characteristic of public health. According to the World Health Organization, the birth rate of children with cleft lip and palate is on average 1:750 newborns, which is 20-30% of all human malformations and 86% of maxillofacial malformations. They contribute significantly to infant morbidity and disability as well as millions of dollars in health care costs each year. Development of the human skull begins about 23-26 days after fertilization, when a multipotent population of cranial neural crest cells migrates from the dorsal part of the neuraxis to the embryonic head region, giving rise to the frontal bone and interparietal part of the occipital bone, while the rest of the cranial arch comes mainly from the mesoderm. A malformation is a deviation from the normal development of an organ or tissue. Among the causes are chromosomal abnormalities, single gene defects, teratogenic or multi-factor agents, that is, a combination of genetic and external factors; the smallest number of cases are idiopathic. Exogenous causes of human congenital abnormalities include: physical (mechanical, thermal, radiation); chemical (hypoxia, malnutrition, hormonal discordance, teratogenic poisons); biological (viruses, bacteria and their toxins, protozoa); mental factors. Endogenous causes are heredity (changes in hereditary structures, mutations); biological inadequacy of germ cells (endocrine disorders, “over-ripening” of germ cells); parents’ age. Congenital craniofacial abnormalities are caused by improper growth and/or development of the brain and facial parts of the skull and soft tissue. Craniofacial abnormalities affecting the skull include macrocephaly, microcephaly and unilateral deformities. Sometimes cranial sutures fuse too early and craniosynostosis occurs, which is accompanied by various cranial deformities. This leads to abnormal cranial development, which can cause dysmorphia, and in the most severe cases catastrophically affect brain development. Conclusion. Based on the analysis of the literature sources, an attempt has been made to summarize the existing information and classifications of congenital cranial abnormalities, as well as the interpretation of various anomalies of the brain and facial skull in alphabetic order. The most common stigmas and malformations of the skull bones are briefly characterized

The Impact of Virtual Surgical Planning on Orthognathic Surgery: A Comparison of 2 Specialties

PURPOSE: Virtual surgical planning (VSP) is the gold standard for preoperative treatment planning for orthognathic surgery.1 Prior to the implementation of VSP, traditional orthognathic preoperative preparation required hours of labor and utilization of a dental laboratory. This often limited orthognathic surgery to providers with dental training. The combination of VSP and 3-dimensional printing has allowed orthognathic surgeons the ability to more accurately and efficiently create treatment plans for these cases.2 This technology has also allowed practitioners such as plastic surgeons to begin to perform orthognathic procedures. This review serves to illustrate how plastic surgeons use VSP and highlight its impact on surgical outcomes and research output within orthognathic surgery. METHODS: A literature search was conducted in the PubMed database to identify all articles published before January 2020 that report perioperative use of VSP technology in orthognathic surgeries. Only articles that were written in English, involved operations on live human patients, and used VSP to plan or assist with orthognathic surgery were included in the analysis. All articles that fit inclusion criteria were reviewed to determine the year of publication, type of orthognathic surgery performed, how VSP was used, and the primary outcomes measured. RESULTS: A total of 419 publications regarding VSP in orthognathic surgery resulted from initial search. Of them, 244 publications were authored by oral and maxillofacial surgeons, 28 publications by plastic surgeons, and 34 by surgeons with training in both fields. TEMPORAL TREND OF PUBLICATIONS: Prior to the late 1990s, VSP in orthognathic surgery publications was primarily authored by oral and maxillofacial surgeons. Plastic surgeons first began publishing on VSP technology for orthognathic surgery in 1998. Since then, there has been a rising trend in plastic surgery usage of VSP paralleled by increasing VSP publications in the field, with 2 publications before the year 2010 (7.2%), 9 from 2010 to 2015 (32%), and 18 between 2015 and 2019 (64%). CATEGORIES OF PUBLICATIONS: Most publications from oral and maxillofacial trained surgeons highlight optimal positioning of craniofacial bones, anticipated stability and functionality of occlusion, and the interplay between orthodontic treatments and orthognathic surgery. In contrast, plastic surgeon authored papers often discuss postoperative facial aesthetics by ensuring facial symmetry and treatment especially in the cases of congenital craniofacial abnormalities like cleft lip/palate, Treacher-Collins, and hemifacial microsomia. CONCLUSIONS: VSP is an increasingly utilized tool that reduces the workflow without compromising accuracy and outcomes in orthognathic surgery. This is the first paper to create a temporal relationship between a new technology and the emergence of plastic surgeons into a field typically predominated by oral and maxillofacial surgeons. As plastic surgeons become more familiar with this technology, they have produced literature that provides alternative perspectives on orthognathic surgery that will push the field forward. REFERENCES: 1. Langdon J, Patel M, Brennan P. Operative Oral and Maxillofacial Surgery. 2nd ed. CRC Press; 2010. 2. Baker SB, Goldstein JA, Seruya M. Outcomes in computer-assisted surgical simulation for orthognathic surgery. J Craniofac Surg. 2012;23:509–513.

The anti-epileptic drug valproic acid causes malformations in the developing craniofacial skeleton of zebrafish larvae

Valproic acid (VPA) is an anti-epileptic drug known to cause congenital craniofacial abnormalities, including orofacial clefts (OFC). The exact mechanisms by which VPA leads to craniofacial skeletal malformations are poorly understood. In this study, we investigated the effects of VPA on cartilage and bone formation in the zebrafish larval head during 1–13 hpf (early) and 25–37 hpf (late) development in which cranial neural crest cells (CNCCs) arise and then proliferate and differentiate, respectively. Double-staining for cartilage and bone at 5 dpf revealed that VPA reduced cartilage and bone formation in a dose-dependent manner after both early or late exposure. Several different CNCC-derived cartilage and bone elements were affected in both groups. In the early group (100 μM VPA), the posterior head length and the ethmoid plate were reduced in length (both p < 0.01), while mineralization of 4 out of 9 bone elements was often lacking (all p < 0.01). In the late group (100 μM VPA), also the posterior head length was reduced as well as the length of the ceratohyals (both p < 0.01). Similar to early exposure, mineralization of 3 out of 9 bone elements was often lacking (all p < 0.01). These results indicate that both CNCC formation (early) and differentiation (late) are hampered by VPA treatment, of which the consequences for bone and cartilage formation are persistent at 5 dpf. Indeed, we also found that the expression of several genes related to cartilage and bone was upregulated at 5 dpf. These data indicate a compensatory reaction to the lack of cartilage and bone. Altogether, VPA seems to induce craniofacial malformations via disturbed CNCC function leading to defects in cartilage and bone formation.

Airway management in children with cleft palate and/or micrognathia

Abstract Cleft lip and/or palate is the commonest congenital craniofacial abnormality affecting approximately 1 in 700 newborns each year. It comprises of a heterogenous group of disorders affecting facial growth and cosmesis, that are associated with increased risk of airway obstruction, sleep disordered breathing (SDB), glue ear and chronic ear disease, feeding difficulties, and failure to thrive (FTT). Cleft palate (CP) can be accompanied by an abnormally undersized jaw, known as micrognathia; although micrognathia can also be found in isolation. The craniofacial abnormalities found in these children can lead to a reduction in airway size due to the tongue falling backwards. The risk of airway obstruction ranges from intermittent airway collapse during sleep (obstructive sleep apnoea, OSA) to potentially life-threatening airway compromise necessitating intubation or a tracheostomy. This paper sets out to describe the pathophysiology of airway compromise in these children, recognising clinical symptoms and appropriate referral strategy, as well as a broad range of management options.

Spontaneous cerebrospinal fluid rhinorrhea in a patient with Pallister–Hall syndrome

Pallister-Hall syndrome (PHS) is extremely rare autosomal dominant disorder with typical clinical features such as presence of polydactyly, hypothalamic hamartoma, bifid epiglottis, anal, renal, genitourinary and pulmonary abnormalities, mainly located in the midline of the body. Spontaneous cerebrospinal fluid (CSF) rhinorrhea is also a rare condition, and it is used to describe nasal discharge of CSF unrelated to previous trauma, localized tumour, surgery, or previous radiation therapy. The exact cause is not yet fully understood.&#x0D; We report a case of adult female patient previously diagnosed with PHS and late onset of spontaneous nasal liquorrhea, due to defect in the anterior skull base. Although it can be incidental finding, we believe that described defect in the body midline can be another presentation of congenital craniofacial abnormality which are common in PHS.

Outcomes of primary powered endoscopic dacryocystorhinostomy in syndromic congenital nasolacrimal duct obstruction

ABSTRACTPurpose: To evaluate the outcomes of powered endoscopic dacryocystorhinostomy (DCR) in syndromic individuals with congenital nasolacrimal duct obstruction (CNLDO).Methods: A retrospective multicenter case series of patients who required a primary powered endoscopic DCR for refractory CNLDO associated with syndromes or congenital craniofacial abnormalities was performed. A minimum follow-up of more than 6 months was considered for final analysis. Main outcome measures were anatomical and functional success at the last follow up.Results: Twenty primary powered endoscopic DCR’s were performed in 12 patients (7 males, 5 females) with syndromic anomalies. The mean age at the time of surgery was 7.6 years (range: 2–22 years). The associated systemic anomalies were Down syndrome (42%, 5/12), ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome (17%, 2/12), gross craniofacial dysgenesis (25%, 3/12) Tessier cleft type 3 (8%, 1/12) and velocardiacfacial syndrome (8%, 1/12). Proximal system agenesis of the upper or lower canaliculus was present in 42% of patients (5 patients, 9 eyes). Adjunctive treatment in the form of Mitomycin C and/or intubation was performed in 55% (11/20) eyes. At a mean postoperative follow-up of 20 months, successful outcomes were noted in 95% of the eyes (19/20). The one eye with an anatomical failure was secondary to a complete cicatricial closure of the ostium and was successfully treated subsequently with a revision endoscopic DCR.Conclusion: Primary powered endoscopic DCR has good outcomes in patients with a CNLDO associated with craniofacial syndromes.

Respiratory Polysomnographic Findings in Patients Treated Primarily for Unilateral Cleft Lip and Palate.

Cleft lip and palate (CLP) is the most common congenital craniofacial abnormality. Obstructive sleep apnea syndrome (OSAS) is a highly prevalent but underdiagnosed disease and is frequently associated with craniofacial anomalies. There are few studies describing the sleep breathing pattern of children with CLP. This study sought to characterize the respiratory profile of 23 children with unilateral cleft lip and palate, aged 7-12 years, who had undergone cleft lip and nasal repair at age 3-4 months and palatoplasty at 12-15 months, with a particular focus on evaluating the presence of OSAS in children with CLP. Polysomnography was performed and findings were analyzed descriptively. We found a mean and median for apnea/hypopnea index (AHI) of 1.11/h (SD = 0.78) and 0.9/h, respectively. The mean obstructive apnea index (OAI) was 0.27/h (SD = 0.38) and the median, 0.1/h. Nearly 30% of patients had an AHI above 1.4 events/h. There was no significant oxyhemoglobin desaturation in the study group. In this group, the prevalence of OSAS was higher than in noncleft populations when compared to the normality values adopted. This sample of patients with unilateral cleft lip and palate exhibited an increased prevalence of OSAS during the mixed dentition stage. Although the results showed that OSAS was mild, we advise closer observation of these patients. Polysomnography is recommended for the assessment of children with airway abnormalities, to individualize the extent of treatment.

The association of cleft lip and palate with cervical vertebral anomalies- a lateral cephalographic study

Background: Cleft lip and palate is the most common major congenital craniofacial abnormality noted, which is 1 in 700 births. Although inheritance may play a role, cleft lip and palate is considered to be of multifactorial etiology, including chemical exposures, radiation, maternal hypoxia, teratogenic drugs, nutritional deficiencies, especially folic acid and cervical vertebral anomalies.Objective: To assess an association between cleft lip and palate and cervical vertebral anomalies.Methodology: The lateral cephalographs of 74 cleft lip and palate patients aged 6- 20yr were traced for cervical spine from C1- C4 on an acetate paper. Cervical vertebral anomalies were recorded and categorized into posterior arch deficiencies and fusion or both.Results: 12.16% of cleft lip and palate patients had cervical vertebral anomalies.Conclusion: The association between cleft lip and palate and cervical vertebral anomalies indicates that cervical vertebral anomalies may be implicated in the etiology of cleft lip and palate. Cervical vertebral anomalies can predispose to further disorders and identification of such anomalies mandates referral to the concerned specialist for appropriate management.

The difference uses of panoramic photo and cbct evaluation of the gnathoplasty surgery outcome

Objective: Gnathoschisis is the most common congenital craniofacial abnormality in patients with cleft lip and/or palate (CL and/or P). The panoramic radiograph is one means to establish a diagnosis and treatment plan with two-dimension photograph. The cone-beam computed tomography (CBCT) is one means of supporting the maxillofacial to get a three-dimension photograph. The aim of this study was to determine the difference in the results of the use of panoramic photos and CBCT in evaluation before and after gnathoplasty surgery.Material and Methods: This is an observational descriptive research with cross-sectional study method. All samples that meet the suitable criteria are put in this research. The data gained by collecting status card at medical record installation about photo panoramic application in gnathoschisis patients was then compare to the examination with CBCT.Results: The result performed shows that there is a significant difference between panoramic and CBCT picture. The CBCT provide better evaluation about teeth age and segment position of jaw curve from the cleft size. While the panoramic photo provides a widely covered area to observe facial and teeth bone.Conclusion: The CBCT results are more accurate in evaluating gnathoplasty surgery than panoramic photo; however, exposure to the radiation should be considered.

A Comprehensive Study of Palate Development in Miniature Pig.

Palate development is an important morphogenetic event in facial development, including the fusion of the lateral and medial nasal portions of the frontonasal process and maxilla. Derailments of any of these events may result in cleft palate, the most frequent congenital craniofacial abnormality. Recent research has shown that the microanatomy of the miniature pig oral maxillofacial region is quite similar to that of humans, and the use of miniature pigs as a large animal model for dental and orofacial research is increasing. Little information is available, however, about the development of the miniature pig palate. Here, using histological and ultrastructural methods, we describe the developmental stages of the palate in miniature pigs. Sections from E26, E30, E35, E40, E45, and E50 embryos were stained with hematoxylin-eosin, and selected specimens were also processed for electron microscopy. The development of the miniature pig palate can be divided into four stages: growth of the bilateral palatal shelves alongside the tongue at E30; elevation of the horizontal position above the tongue at E35; establishment of bilateral shelf contact at the midline from E35-50; and a final fusion step at E50, similar to the mouse and human. The histological characteristics of the miniature pig palate at different developmental stages were synchronously verified at the ultrastructural level. Our study provides a piece of first-hand data regarding palate morphological organogenesis in the miniature pig and a foundation for further research with this model to explore mechanisms of cleft palate development. Anat Rec, 300:1409-1419, 2017. © 2017 Wiley Periodicals, Inc.

Effect of gentamicin and levels of ambient sound on hearing screening outcomes in the neonatal intensive care unit: A pilot study

ObjectiveHearing loss rates in infants admitted to neonatal intensive care units (NICU) run at 2–15%, compared to 0.3% in full-term births. The etiology of this difference remains poorly understood. We examined whether the level of ambient sound and/or cumulative gentamicin (an aminoglycoside) exposure affect NICU hearing screening results, as either exposure can cause acquired, permanent hearing loss. We hypothesized that higher levels of ambient sound in the NICU, and/or gentamicin dosing, increase the risk of referral on the distortion product otoacoustic emission (DPOAE) assessments and/or automated auditory brainstem response (AABR) screens. MethodsThis was a prospective pilot outcomes study of 82 infants (<37 weeks gestational age) admitted to the NICU at Oregon Health & Science University. An ER-200D sound pressure level dosimeter was used to collect daily sound exposure in the NICU for each neonate. Gentamicin dosing was also calculated for each infant, including the total daily dose based on body mass (mg/kg/day), as well as the total number of treatment days. DPOAE and AABR assessments were conducted prior to discharge to evaluate hearing status. Exclusion criteria included congenital infections associated with hearing loss, and congenital craniofacial or otologic abnormalities. ResultsThe mean level of ambient sound was 62.9 dBA (range 51.8–70.6 dBA), greatly exceeding American Academy of Pediatrics (AAP) recommendation of <45.0 dBA. More than 80% of subjects received gentamicin treatment. The referral rate for (i) AABRs, (frequency range: ∼1000–4000 Hz), was 5%; (ii) DPOAEs with a broad F2 frequency range (2063–10031 Hz) was 39%; (iii) DPOAEs with a low-frequency F2 range (<4172 Hz) was 29%, and (iv) DPOAEs with a high-frequency F2 range (>4172 Hz) was 44%. DPOAE referrals were significantly greater for infants receiving >2 days of gentamicin dosing compared to fewer doses (p = 0.004). The effect of sound exposure and gentamicin treatment on hearing could not be determined due to the low number of NICU infants without gentamicin exposure (for control comparisons). ConclusionAll infants were exposed to higher levels of ambient sound that substantially exceed AAP guidelines. More referrals were generated by DPOAE assessments than with AABR screens, with significantly more DPOAE referrals with a high-frequency F2 range, consistent with sound- and/or gentamicin-induced cochlear dysfunction. Adding higher frequency DPOAE assessments to existing NICU hearing screening protocols could better identify infants at-risk for ototoxicity.

Mutation analysis by direct and whole exome sequencing in familial and sporadic tooth agenesis.

Dental agenesis is one of the most common congenital craniofacial abnormalities. Dental agenesis can be classified, relative to the number of missing teeth (excluding third molars), as hypodontia (1 to 5 missing teeth), oligodontia (6 or more missing teeth), or anodontia (lack of all teeth). Tooth agenesis may occur either in association with genetic syndromes, based on the presence of other inherited abnormalities, or as a non-syndromic trait, with both familiar and sporadic cases reported. In this study, we enrolled 16 individuals affected by tooth agenesis, prevalently hypodontia, and we carried out direct Sanger sequencing of paired box 9 (PAX9) and Msh homeobox 1 (MSX1) genes in 9 subjects. Since no mutations were identified, we performed whole exome sequencing (WES) in the members of 5 families to identify causative gene mutations either novel or previously described. Three individuals carried a known homozygous disease mutation in the Wnt family member 10A (WNT10A) gene (rs121908120). Interestingly, two of these individuals were siblings and also carried a heterozygous functional variant in EDAR-associated death domain (EDARADD) (rs114632254), another disease causing gene, generating a combination of genetic variants never described until now. The analysis of exome sequencing data in the members of other 3 families highlighted new candidate genes potentially involved in tooth agenesis and considered suitable for future studies. Overall, our study confirmed the major role played by WNT10A in tooth agenesis and the genetic heterogeneity of this disease. Moreover, as more genes are shown to be involved in tooth agenesis, WES analysis may be an effective approach to search for genetic variants in familiar or sporadic tooth agenesis, at least in more severe clinical manifestations.