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.

Anesthetic management in an infant with tetra-amelia syndrome with congenital maxillomandibular fusion: A case report.

A 10-month-old girl who had tetra-amelia syndrome and congenital maxillomandibular fusion (syngnathia) was scheduled for the surgical fusion separation. Anesthetic management for this case was considerably challenging. Standard monitoring was still applied to the patient's extremities. IV access was suspected to be difficult but firmly needed before intubation to provide resuscitation during an emergency. Connecting anesthetic circuit with nasopharyngeal airway was the preferred technique due to its benefits such as maintaining spontaneous ventilation, providing inhaled anesthetic, as well as monitoring oxygenation and ventilation. Importantly, the cornerstones for handling such complicated cases are multidisciplinary approach and teamwork.

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.

Association between craniofacial asymmetry and unilateral temporomandibular joint sounds in adult patients using 3D-computed tomography.

OBJECTIVES: The purpose of this study was to investigate the possible relationship between unilateral temporomandibular joint (TMJ) sounds and craniofacial asymmetry, using 3D-computed tomography (CT) measurements. SUBJECTS AND METHODS: Forty-one reconstructed 3D-CT models of adult subjects were measured to analyze craniofacial asymmetry. Subjects were divided into two groups depending on the presence (n = 20) or absence (n = 21) of unilateral joint sounds, and the results compared using the Mann-Whitney U-test. To investigate the association between these parameters, the Pearson correlation coefficient was calculated. RESULTS: Asymmetries in the maxillary and mandibular structures were statistically significant (P < 0.05) for subjects with unilateral TMJ sounds and for controls, except in the case of maxillary rotation and mandibular ramus height (P > 0.05). The highest deviations found were frontal and lateral ramal inclination, goniac angle and canting of occlusal plane. CONCLUSIONS: Adult patients with unilateral joint sounds may have skeletal jaw asymmetry and a canted occlusal plane.

Dysgnathia complex sine holoprosencephaly nor synotia: a case report and discussion of its nosology.

A severe mandibular hypoplasia and microstomy with intraoral anomalies including hypoglossia, fused gums, persistence of buccopharyngeal membrane, and laryngeal hypoplasia were noted in a female newborn with the dysgnathia complex (DC). Additionally, our proposita also presented natal teeth as a probably new finding. These clinical manifestations overlapped with those of the fourth report of hypomandibular faciocranial syndrome (HFS) (31), and given that both lack for craniosynostosis (pathognomonic of HFS), we considered that both represent a subtype of DC proposed as DC sine holoprosencephaly nor synotia (DCSHS). Differential characteristics between the DCSHS, the HFS, and the DC with holoprosencephaly sine synotia are reviewed and additionally, we discussed some aspects about the nosology of the DC.

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.

Morphologic relationship between the cranial base and the mandible in patients with facial asymmetry and mandibular prognathism.

INTRODUCTION: This study was conducted to measure the dimensional changes in the cranial base and the mandible in patients with facial asymmetry and mandibular prognathism, and to examine the morphologic relationship between asymmetries of the cranial base and the mandible. METHODS: The patients were 60 adults with mandibular prognathism, divided into a symmetry group (menton deviation, <2 mm; n = 30) and an asymmetry group (menton deviation, >4 mm; n = 30) according to the degree of menton deviation. Three-dimensional computed tomography scans were obtained with a spiral scanner. Landmarks were designated on the reconstructed 3-dimensional surface models. Linear, angular, and volumetric measurements of the cranial base and mandibular variables were made. RESULTS: In the asymmetry group, the hemi-base, anterior cranial base, and middle cranial base volumes were significantly larger (P <0.01), and crista galli to sphenoid, sphenoid to petrous ridge, anterior clinoid process to petrous ridge, and vomer to petrous ridge lengths were significantly longer (P <0.05) on the nondeviated side than on the deviated side. Menton deviation was significantly correlated with the difference in hemi-base volume, and ramal volume was significantly correlated with the difference in hemi-base and middle cranial base volumes between the nondeviated and deviated sides (P <0.05). CONCLUSIONS: In patients with facial asymmetry and mandibular prognathism, cranial base volume increased on the nondeviated side and was also correlated with mandibular asymmetry.

Rare variant of dens invaginatus with accessory root and labial talon cusp in maxillary lateral incisor-Case report.

Dens invaginatus (DI) often causes dysmorphic changes in both the crown and root. This case report presents a complicated type 3a DI in a maxillary lateral incisor with labial talon cusp and root bifurcation. Although lingual talon cusp is common in maxillary lateral incisor, labial talon cusp is rare. An auxiliary palatal root in maxillary lateral incisor is also unusual. No such case involving all three variations has been described in the literature. The DI was classified as type B4 according to Schulze and Brand, as it involved division of pulp and root. DI was managed by orthograde MTA, radisectomy and periodontal regeneration was done for the palatal root. Labial talon associated with DI and can lead to early periodontal/pulpal involvement. Type 3 DI can affect the root with marked dilatation and division. Additional palatal root should be carefully detected in type 3a DI and managed with the aid of CBCT.

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.

Bilateral Marcus Gunn jaw winking synkinesis with monocular elevation deficiency: a case report and literature review.

Marcus Gunn jaw winking synkinesis (MGJWS) occurs due to an aberrant innervation of the levator palpebrae superioris muscle by a branch of the motor division of the trigeminal nerve that supplies the muscles of mastication. MGJWS is mostly unilateral occurring in isolation and is less frequently associated with ocular or systemic abnormalities. Although MGJWS is mostly unilateral, few bilateral cases have been reported. Here we describe a rare case of bilateral MGJWS in an 18 year-old male patient with asymmetric bilateral ptosis and monocular elevation deficiency in the right eye.

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.

"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.

Congenital syngnathia: case report and review of literature.

Congenital bony fusion of the maxilla and mandible, especially as an isolated occurrence, is a very rare condition. The very few cases reported in the literature are mostly inadequate in description and confusing in nomenclature. An isolated case of syngnathia in a 60-year-old female patient with unilateral bony fusion (synostosis) of the maxilla and mandible associated with fibrous adhesions (synechiae) of the opposite site is reported. The existent literature is also reviewed.

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.

Brain malformation in single median maxillary central incisor.

Clinical and radiographic examinations and MR scan of a 12-year-old girl with SMMCI (single median maxillary central incisor) showed impaired growth and a midline defect involving the central incisor, cranium and the midline structures in the brain, falx cerebri and pituitary gland. She had a severe growth hormone deficiency but no other pituitary hormone deficiencies. She was treated with growth hormone and followed during a four-year period with successful gain in body height and sexual maturation. This study focuses on the developmental association between the involved structures and provides guidelines for early diagnostics.

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.

Periodontal mechanoreceptors and bruxism at low bite forces.

OBJECTIVE: In this study, we examined if 6-9 Hz jaw tremor, an indirect indicator of Periodontal Mechanoreceptor (PMR) activity, is different in bruxists compared to healthy participants during production of a low-level constant bite force. METHODS: Bite force and surface EMG from the masseter muscle were recorded simultaneously as participants (13 patients, 15 controls) held a force transducer between the upper and lower incisors very gently. RESULTS: Tremor in 6-9 Hz band for bruxists was greater on average compared to controls, but the difference was not significant, both for force recordings and EMG activity. CONCLUSIONS: The low effect sizes measured with the current protocol contrast highly with those of our previous study, where larger, dynamic bite forces were used, and where jaw tremor was markedly different in bruxists compared with controls. SIGNIFICANCE: We have now gained important insight into the conditions under which abnormal jaw tremor can be elicited in bruxism. From a scientific standpoint, this is critical for understanding the 'abnormality' of PMR feedback in bruxism. From a clinical perspective, our results represent progress towards the development of an optimal protocol in which jaw tremor can serve as a biological marker of bruxism.

Marcus Gunn (jaw-winking) phenomenon in pediatric otorhinolaryngology practice.

Marcus Gunn phenomenon (MGP) is a rare form of congenital facial synkinesis known as jaw-winking or pterygoid-levator synkinesis. The MGP is the raising of the affected eyelid is synchronous and proportionate to the opening of the mouth. The etiology is unclear. Most authors claim that a branch of trigeminal nerve has been congenitally misdirected into position of the oculomotor nerve which supplies the levator muscle of the upper lid. The MGP deals with number of problems which have to be manage by ENT doctors, but they are not well­documented. We describe the first time Marcus Gunn phenomenon associated with an olfactory nerve disturbance. We have especially emphasized laryngological aspect of MGP diagnosis and the need for deeper interdisciplinary diagnostics in each child with olfactory dysfunction.

Solitary median maxillary central incisor syndrome occurring together with oromandibular-limb hypogenesis syndrome type 1: a case report of this previously unreported combination of syndromes.

BACKGROUND: Solitary median maxillary central incisor syndrome is a unique developmental abnormality, involving the central incisor tooth germs, occurring with and without systemic involvement. This syndrome has been recorded in association with many other midline developmental anomalies and several known syndromes. Its presence, together with oromandibular-limb hypogenesis syndrome type 1, has not previously been reported. CASE REPORT: A 3-year-old girl was presented with early childhood caries and a solitary median maxillary central incisor. She had a median submucosal cleft palate and severe micrognathia with hypoglossia. In addition, she had short stature, eating difficulty, and hearing and speech problems. Comprehensive dental treatment for severe early childhood caries was accomplished with a 3-month follow-up appointment to monitor the oral health. The multidisciplinary consultation important for further management has been established. CONCLUSION: The results suggested that when a solitary median maxillary incisor tooth presents, a paediatrician and a geneticist should be asked to carefully examine the patient for other craniofacial malformations and especially midline systemic problems.