A Recurrent Nonsense Mutation in NECTIN4 Underlying Ectodermal Dysplasia-Syndactyly Syndrome with a Novel Phenotype in a Consanguineous Kashmiri Family.

EDSS1, a syndrome characterized by ectodermal dysplasia-syndactyly, is inherited in an autosomal recessive manner due to mutations in the NECTIN4/PVRL4 gene. Clinical manifestations of the syndrome include defective nail plate, sparse to absent scalp and body hair, spaced teeth with enamel hypoplasia, and bilateral cutaneous syndactyly in the fingers and toes. Here, we report a consanguineous family of Kashmiri origin presenting features of EDSS1. Using whole exome sequencing, we found a recurrent nonsense mutation (NM_030916: c.181C > T, p.(Gln61 ∗)) in the NECTIN4 gene. The variant segregated perfectly with the disorder within the family. The candidate variant was absent in 50 in-house exomes pertaining to other disorders from the same population. In addition to the previously reported clinical phenotype, an upper lip cleft was found in one of the affected members as a novel phenotype that is not reported by previous studies in EDSS1 patients. Therefore, the study presented here, which was conducted on the Kashmiri population, is the first to document a NECTIN4 mutation associated with the upper lip cleft as a novel phenotype. This finding broadens the molecular and phenotypic spectrum of EDSS1.

Cleft palate-lateral synechiae syndrome: a case report.

Cleft palate-lateral synechiae syndrome (CPLSS) is an extremely rare congenital malformation syndrome with undetermined etiology, characterized by a cleft palate and lateral intraoral synechiae linking the free borders of the palate to the mouth floor. We report a case of a female neonate, admitted for suckling difficulties with a cleft lip and palate associated to multiple lateral intraoral synechiae. Resection of the synechiae allowed oral feeding. Cleft palate-lateral synechiae syndrome is an exceptional syndrome as only seventeen cases have been reported in the literature. Synechiae can be isolated or more frequently in association with other congenital anomalies such as cleft lip and/or palate. These synechiae can cause functional deficits, especially in the respiratory and feeding tracts, language disorders or recurrent otitis. Although it is exceptional, this malformative entity must be known by medical practitioners in order to set up a well-adapted therapeutic protocol.

CHARGE syndrome without colobomas: Ophthalmic findings.

To report ophthalmic findings of patients without colobomas, and with a clinical and molecular diagnosis of CHARGE Syndrome. Retrospective study of ophthalmic findings in 67 CHARGE patients-clinically confirmed diagnosis with positive CHD7 mutation-seen in the Ophthalmology department of Cincinnati Children's Hospital Medical Center between January 1, 2008 through September 25, 2018. Criteria for inclusion in this study was absence of any form of a coloboma in either eye. In our cohort, all patients had a positive CHD7 mutation, in addition to a clinical diagnosis. 19.4% (13/67) of CHARGE patients did not have a coloboma in either eye. 69.2% (9/13) had strabismus, 76.9% (10/13) had a refractive error that warranted refractive correction, 23.1% (3/13) had amblyopia, 38.5% (5/13) had nasolacrimal duct obstruction, 30.8% (4/13) had dry eye syndrome and exposure keratopathy, 15.4% (2/13) had ptosis, 15.4% (2/13) had blepharitis, 15.4% (2/13) had Cortical Visual Impairment, 7.7% (1/13) of patients had optic nerve drusen, 7.7% (1/13) had Marcus Gunn Jaw Winking, and 7.7% (1/13) with an eyelid nevus. There are numerous ophthalmic findings in individuals with CHARGE Syndrome without colobomas. No study to date has evaluated the ophthalmic findings in CHD7 positive CHARGE patients without colobomas. These findings need to be assessed and treated to ensure optimal vision in the CHARGE patient population. Absence of coloboma does not rule out a diagnosis of CHARGE syndrome, and if there is a clinical suspicion, clinical confirmation then genetic testing would be warranted.

Impact of orthognathic surgery on the body posture.

BACKGROUND: Postural control is classically described as being based on the visual, vestibular, and proprioceptive musculo-articular sensory systems. The influence of mandibular proprioception on postural stabilization remains controversial. Most previous studies analyzed how postural stability is influenced by partial changes in mandibular proprioception (dental occlusion and jaw position). RESEARCH QUESTION: In the present experiment, we asked whether drastic mandibular changes, resulting from orthognathic surgery (including dental, joint and muscular efferents), modify postural control. METHODS: The analyzes were performed in 22 patients tested before, and 2.5 months, after orthognathic surgery for treatment of dysmorphic jaws. Experiments were performed under 4 experimental conditions: 2 visual conditions: Eyes Open (EO) and Eyes Closed (EC), and 2 occlusal conditions: Occlusion (OC: mandible positioned by the contact of the teeth), and Rest Position (RP: mandible positioned by the muscles without tooth contact). The analyses focused on head orientation in the frontal plane and on postural stabilization in a static task, consisting of standing upright. RESULTS: The results show that, 2.5 months after orthognathic surgery, head orientation in the frontal plane was improved, since patient's external intercanthal lines became closer to the true horizontal line when they were tested EC and in OC condition. Postural responses, based on the wavelet transformation data, highlight an improvement in maintaining an upright stance for all the tested sensory conditions. However, such improvement was greater in the EC and RP conditions. SIGNIFICANCE: These results show, for the first time, that after drastic mandibular changes, the weight of proprioceptive cues linked to the mandibular system may be so enhanced that it may constitute a new reference frame to orient the head in space, in darkness, and improve static postural stabilization, even in the presence of visual cues.

Using cone beam CT to assess the upper airway after surgery in children with sleep disordered breathing symptoms and maxillary-mandibular disproportions: a clinical pilot.

BACKGROUND: The surgical excision of anatomic obstructions such as adenoids, palatine or lingual tonsils are commonly performed in children with sleep disordered breathing (SDB). Imaging studies measuring airway changes post-surgery in the SDB pediatric population are scarce, rarely addresses the nasal cavity, and are based on global measures (e.g. volume) that do not represent the complexity of the upper airway anatomy. The purpose of this pilot is to test the feasibility in using cone beam CT (CBCT) to analyze the nasal and pharyngeal airway space post-surgery using meaningful methods of analyses, and correlating imaging findings with clinical outcomes in children with SDB symptoms and maxillary-mandibular disproportion. METHODS: Twelve non-syndromic children with SDB symptoms and jaw disproportions were evaluated by interdisciplinary airway team before and after upper airway surgery. CBCT and OSA-18 quality of life questionnaire pre and post-operatively were completed. Conventional and new airway variables were measured based on 3D models of the upper airways and correlated with OSA-18. Conventional measures include volume, surface area, and cross-sectional area. New airway measures include constriction and patency; point-based analyses. RESULTS: Eight females and four males were 8.8 ± 2 years with mean BMI of 18.7 ± 3. OSA-18 improved, median (lower quartile-upper quartile) from 64.2 (54.7-79.5) to 37.6 (28.7-43) postoperatively, p < 0.001. The median of all airway measures improved however with very wide range. Subjects with the smallest amounts of constriction relief and/or gain in airway patency presented with least improvement in OSA-18. New airway measures show strong correlation with changes in OSA-18 (ρ = 0.44 to 0.71) whereas conventional measures showed very weak correlation (ρ = -0.04 to 0.37). CONCLUSIONS: Using point-based analyses, new airway measures better explained changes in clinical symptoms compared to conventional measures. Airway patency gained by at least 150% and constriction relief by at least 15% showed marked improvement in OSA-18 by 40-55%, after surgery in the tested cohort.

Bilateral coronoid hypoplasia and complex odontoma: a rare concurrence of developmental pathology and odontogenic tumour of the mandible.

We present a rare case of concurrent bilateral coronoid hypoplasia and complex odontoma in the mandible, with replacement of missing posterior teeth in both sides of the lower jaw. A 20-year-old woman was diagnosed with bilateral occurrence of coronoid hypoplasia and unerupted complex odontoma after radiographic and histopathological examination. The patient was surgically treated with complete removal of the unerupted complex odontoma and prosthetic replacement of the missing teeth.

Plurimalformative syndrome associating trisomy 18 and omphalocele. Case report and review of the literature.

Trisomy 18 or Edwards syndrome is a rare chromosomal anomaly, associated with mild to severe intellectual disabilities and multiple congenital anomalies. Trisomies 18 and 13 are lethal, only 5-10% of patients surviving the first year of life. Although prenatal biological and ultrasound investigations are mandatory and free and the detection rate of chromosomal abnormalities is high, the birth of children with no real chance at a normal life being thus avoided by therapeutic abortion, the parents of the here presented child did not benefit from medical examination or prenatal tests, unfortunately the case of many families in Romania. The policy of limiting medical intervention in newborns with Edwards syndrome due to the broad spectrum of severe congenital malformations, severe mental retard and reduced life expectancy is unanimously accepted, but yet difficult to apply from an ethical point of view. That is why very important for both healthcare providers and families to have accurate and detailed knowledge of survival, disease course, and quality of life so that they can make fully informed decisions regarding care of these babies. The particularity of this case is the association of multiple congenital anomalies in a male newborn with trisomy 18, almost all apparata and systems being affected, with the presence of an omphalocele and complete right labiopalatine cleft, which are less frequent at children with trisomy 18.

Three-dimensional virtual operations can facilitate complicated surgical planning for the treatment of patients with jaw deformities associated with facial asymmetry: a case report.

This article describes a case we experienced in which good postsurgical facial profiles were obtained for a patient with jaw deformities associated with facial asymmetry, by implementing surgical planning with SimPlant OMS. Using this method, we conducted LF1 osteotomy, intraoral vertical ramus osteotomy (IVRO), sagittal split ramus osteotomy (SSRO), mandibular constriction and mandibular border genioplasty. Not only did we obtain a class I occlusal relationship, but the complicated surgery also improved the asymmetry of the frontal view, as well as of the profile view, of the patient. The virtual operation using three-dimensional computed tomography (3D-CT) could be especially useful for the treatment of patients with jaw deformities associated with facial asymmetry.

Combined multisegmental surgical-orthodontic treatment of bialveolar protrusion and chin retrusion with severe facial asymmetry.

LeFort I osteotomy, anterior segmental osteotomy, bilateral sagittal split ramus osteotomy, and genioplasty are frequently used methods for correcting facial deformities. However, in patients with an abnormally shaped maxilla or mandible, more complex surgical techniques or multiple combinations must be considered for improved esthetic results. This article presents a patient with bialveolar protrusion, mandibular prognathism, chin retrusion, a long face, and severe facial asymmetry. A combination of LeFort I asymmetric impaction, anterior segmental osteotomy, and 3-piece segmentation of the maxilla, and bilateral sagittal split ramus osteotomy, anterior segmental osteotomy, genioplasty advancement, and angle shaving in the mandible were conducted simultaneously. In patients with complicated deformities that cannot be classified by simple conventional classification methods, multisegmental osteotomy can be an option for improved esthetic results.

Correction of facial asymmetry resulting from hemimandibular hyperplasia: surgical steps to the esthetic result.

Hemimandibular hyperplasia is a facial deformity in which there is an increase in the condyle, neck of the condyle or ramus, and an occlusal cant. Different surgical treatments are proposed in the literature, from simple low or high condylectomy to more complex procedures combining osteotomies in different sites of the mandible. Surgical procedure is defined by the scintigraphic diagnosis of activity or inactivity in the center of condylar growth. The case report describes a 35-year-old female patient with hemimandibular hyperplasia on the left side with inactivity of condylar growth, successfully treated with bilateral sagittal split ramus osteotomy associated with a basilar osteotomy in form of "L" on the affected side. The surgical technique was easily executed, with an improvement in function, aesthetics, and patient satisfaction. Correction of facial asymmetry caused by excessive growth of the mandible using this basilar osteotomy in the form of "L" combined with bilateral sagittal split ramus osteotomy proved to be a relatively simple technique of easy execution with a low risk of nerve damage.

Hemimandibular hyperplasia: a rare case of vertical facial asymmetry. A case report.

BACKGROUND: Hemimandibular hyperplasia (HH), also known as hemimandibular hypertrophy, is characterised by excessive unilateral three-dimensional growth of the mandible after birth. Vertical elongation of the mandible on one side becomes clinically evident as a rare form of vertical facial asymmetry. Aberrant growth of the facial skeleton affects the developing dentition and dental compensation is usually unable to maintain optimal occlusal relationships. The resulting malocclusion is best managed surgically to address the various facial, skeletal and dental problems that confront clinicians. AIM: To present a case of hemimandibular hyperplasia treated using a combined surgical-orthodontic approach. METHODS: Combined surgical-orthodontic treatment was accomplished in four phases: 1) presurgical orthodontic, 2) surgical, 3) post-surgical orthodontic and 4) orthodontic retention. Comprehensive records (including photographs, study models and radiographs) were taken at the pre-treatment, pre-surgery and debanding stages of treatment. RESULTS: A significant improvement in facial symmetry and a positive occlusal outcome were achieved. A more balanced gingival display has improved the patient's smile aesthetics. CONCLUSION: Hemimandibular hyperplasia is a rare condition causing vertical facial asymmetry and a resulting malocclusion. A combined surgical-orthodontic approach is able to accomplish sound facial, skeletal and dental treatment outcomes.

Congenital maxillomandibular fusion: a report of three cases.

Congenital fusion of the mandible to the maxilla (syngnathia) is a rare disorder. The first case was reported in 1936 and only a few cases have been reported in the literature since then. This paper reports three new cases of syngnathia. Clinical and radiographic features are presented, as well as surgical management and complications.

"See-saw" Marcus Gunn syndrome.

The authors report an unusual case of Marcus Gunn syndrome in an adult patient, characterized by classical Marcus Gunn on one side and inverse Marcus Gunn on the other side. The patient exhibited a "see-saw" kind of eyelid movement on opening and closing the mouth and on moving the jaw from side to side. This clinical entity has been reported very rarely. A similar but etiologically different acquired condition seen commonly in adults, Marin Amat syndrome, is also discussed.

Hypoglossia-hypodactyly syndrome in a newborn.

Hypoglossia-hypodactyly syndrome is characterised by small tongue associated with limb deficiency. It is an extremely rare condition with around 30 cases reported in world literature. We report a case of hypoglossia-hypodactyly syndrome that in addition to features already described also had supernumerary nipples, microcephaly and micropenis with cryptorchidism. Hypodactyly was symmetrical in all four limbs. These features have not been reported previously.

Temporomandibular joint dysfunction and orthognathic surgery: a retrospective study.

BACKGROUND: Relations between maxillo-mandibular deformities and TMJ disorders have been the object of different studies in medical literature and there are various opinions concerning the alteration of TMJ dysfunction after orthognathic surgery. The purpose of the present study was to evaluate TMJ disorders changes before and after orthognathic surgery, and to assess the risk of creating new TMJ symptoms on asymptomatic patients. METHODS: A questionnaire was sent to 176 patients operated at the Maxillo-Facial Service of the Lille's 2 Universitary Hospital Center (Chairman Pr Joël Ferri) from 01.01.2006 to 01.01.2008. 57 patients (35 females and 22 males), age range from 16 to 65 years old, filled the questionnaire. The prevalence and the results on pain, sounds, clicking, joint locking, limited mouth opening, and tenseness were evaluated comparing different subgroups of patients. RESULTS: TMJ symptoms were significantly reduced after treatment for patients with pre-operative symptoms. The overall subjective treatment outcome was: improvement for 80.0% of patients, no change for 16.4% of patients, and an increase of symptoms for 3.6% of them. Thus, most patients were very satisfied with the results. However the appearance of new onset of TMJ symptoms is common. There was no statistical difference in the prevalence of preoperative TMJ symptoms and on postoperative results in class II compared to class III patients. CONCLUSIONS: These observations demonstrate that: there is a high prevalence of TMJ disorders in dysgnathic patients; most of patients with preoperative TMJ signs and symptoms can improve TMJ dysfunction and pain levels can be reduced by orthognathic treatment; a percentage of dysgnathic patients who were preoperatively asymptomatic can develop TMJ disorders after surgery but this risk is low.

Palatal expansion in a patient with solitary median maxillary central incisor syndrome.

The objective of this article was to report a clinical case of a patient with solitary median maxillary central incisor syndrome. He was treated with rapid maxillary expansion and evaluated with computed tomography. The boy, aged 6 years 7 months, had a single maxillary central incisor in the midline, posterior crossbite, prominent midpalatal ridge, indistinct philtrum, no incisive papilla, and no labial frenulum. No other systemic anomalies were found. Posteroanterior cephalometric radiography showed skeletal atresia of the maxilla that was corrected with rapid maxillary expansion. A Haas expander was used and activated twice per day (quarter turn per activation) for 15 days. The procedure was monitored with computed tomography to evaluate any effect on the intermaxillary suture and tooth. Although the crossbite was clinically corrected after the expansion, radiographs and tomographs showed no opening of the midpalatal suture. Rapid maxillary expansion resulted in neither midpalatal suture opening nor transverse increase of the maxillary skeletal base in this patient.

A comparison of autogenous bone graft combined with deproteinized bovine bone and autogenous bone graft alone for treatment of alveolar cleft.

This study assessed the use of composite autogenous bone and deproteinized bovine bone (DBB) for repairing alveolar cleft compared with autogenous bone alone in terms of clinical outcomes and patient morbidity. 30 patients with a mean age of 10.2±1.7 years were randomly divided into two groups. Group I used autogenous cancellous bone graft harvested from the anterior iliac crests by the conventional trapdoor approach. Group II used a composite of DBB and autogenous cancellous bone harvested by a trephine bone collector; the proportion of 1:1 by volume was used. The bone graft quantities of both groups decreased with time. Their average changes were not statistically different over 24 months after grafting. The canines of both groups could spontaneously or orthodontically erupt through the grafting areas. Patients in group II recovered from uncomfortable walking significantly faster than those in group I (p<0.05) and their duration of hospital stay was significantly shorter than those in group I (p<0.05). The average operation time, intra-operative blood loss and postoperative pain were less in group II than in group I (p>0.05).

Congenital fusion of the maxilla and mandible (congenital bony syngnathia).

A rare case of syngnathia (maxillomandibular fusion) is described in a 2-year-old boy who presented from a rural area of Saudi Arabia. The child had the problem since birth and had undergone two surgical attempts to release the fusion at another institution but both had failed and recurrence occurred. In the authors' institute, the patient underwent two separate surgical procedures at the age of 2 and 3 years. Both procedures were followed by a period of aggressive physiotherapy, but the patient presented with re-fusion of the mandible and the maxilla 1 year after the first operation and 5 months after the second operation. It was decided to defer treatment until puberty. The cause of the relapse may be the high osteogenic potential because of his youth or the failure of the parents to maintain the active physiotherapy protocol because they live in a rural area and close follow-up was difficult. A possible genetic predisposition for bone formation at this site should be investigated.