MANDIBULA Extra Quality
We analysed the incidence of a mandibular osteonecrosis (ON) in 189 patients irradiated for a cancer of the oral cavity, or of the oropharynx or epipharynx, with a total target dose of at least 60 Gy between 1980 and January 1994. Target doses per fraction were between 2.0 and 1.2 Gy, number of sessions per week was between 5 and 10, and total target doses were between 60 and 78.2 Gy. No instance of ON has been observed after target doses between 60 and 65 Gy. Cumulative incidence of an ON needing a mandibular resection was: 24.8% in patients treated with a mandibular dose per fraction between 2.00 and 2.22 Gy and a total mandibular dose between 66.00 and 79.70 Gy; 19.6% in patients treated with a mandibular dose per fraction between 1.80 and 1.90 Gy and a total mandibular dose between 69.00 and 75.60 Gy, 2.2% in patients treated with two fractions of 1.20 Gy per day for 5 days in the week with or without simultaneous application of cis-platinum and a total mandibular dose between 75.20 and 82.00 Gy. Dose per fraction, association of the tumour with bone, and the volume of the horizontal ramus of the mandibula irradiated with a high dose were observed to be significant risk factors.
MANDIBULA
The jaw bones receive complicated forces not only through the muscles, but through the teeth directly. Therefore, it is thought that the morphology of the jaw bones are greatly effected by the oral conditions. In this paper, the morphological changes of the mandibula with loss of the teeth are descrived. Furthermore, the three dimensional changes of the trabecular bones observed by micro-CT are shown. The jaw bones are of complex composition since they contain the alveolar sockets that encase the dental roots. The structures of the trabecular bone of the mandibula are constructed in order to support the teeth. The trabecular bones appear to have plate-like shape rather than rod-like shape in the three dimensional observation using micro-CT. With loss of the teeth, the height of the mandibula is rapidly shortened. And in the internal structures, both width and volume of the trabecular bone within the substantia spongiosa are reduced and the trabecular bones run in the irregular course. In addition, the plate-like shaped trabecular bones tend to transform into rod-like shaped ones. Based on these findings, it is suggested that maintenance of the intact teeth is important to keep the normal morphology of the mandibula.
Auriculocondylar syndrome (ARCND) is an autosomal monogenic disorder characterised by external ear abnormalities and micrognathia due to hypoplasia of the mandibular rami, condyle and coronoid process. Genetically, three subtypes of ARCND (ARCND1, ARCND2 and ARCND3) have been reported. To date, five pathogenic variants of GNAI3 have been reported in ARCND1 patients. Here, we report a novel variant of GNAI3 (NM_006496:c.807C>A:p.(Asn269Lys)) in a Japanese girl with micrognathia using trio-based whole exome sequencing analysis. The GNAI3 gene encodes a heterotrimeric guanine nucleotide-binding protein. The novel variant locates the guanine nucleotide-binding site, and the substitution was predicted to interfere with guanine nucleotide-binding by in silico structural analysis. Three-dimensional computer tomography scan, or cephalogram, displayed severely hypoplastic mandibular rami and fusion to the medial and lateral pterygoid plates, which have been recognised in other ARCND1 patients, but have not been described in ARCND2 and ARCND3, suggesting that these may be distinguishable features in ARCND1.
Auriculocondylar syndrome (ARCND) is a rare autosomal dominant or recessive disorder characterised by recognisable malformation of the ears, known as question-mark ears, and micrognathia involving hypoplasia of the mandibular rami, condyle and coronoid process. These orofacial malformations lead to respiratory difficulties, including apnoea. Feeding and speech difficulties due to ankylosis of the temporomandibular joints often become the chief complaints [1].
Here, we present a novel variant in the G4 box of Gαi3 found in a Japanese girl tentatively diagnosed with severe micrognathia and describe recognisable morphological characteristics of the mandibula specific in ARCND1.
The proband was a 2-year-old Japanese girl born to healthy non-consanguineous parents (Fig. 1A). She presented severe mandibular hypoplasia and a rounded facial appearance with prominent cheeks. External ear malformation (question-mark ears) was observed. Oral malformations, such as microstomia, lobular hypoplastic tongue with soft-tissue projections, cleft palate with hypoplastic soft palate and ankylosis of the temporomandibular joints, were also present (Supplementary Figure). She also had difficulties with feeding and speech articulation. Meatal stenosis, malformation of the internal ear (semicircular and cochlear duct) and moderate sensorineural hearing loss were seen. Tracheostomy was performed due to upper airway obstruction. Three-dimensional computed tomography (3D-CT) showed mandibular condyle agenesis, excessively short rami and retrognathia (Fig. 2). The mandibular rami were fused with medial and lateral pterygoid plates. Both her mandibular angles were unclear. The intracranial structure, nasal cavity, orbital cavity and maxilla were normal. No other general malformations, growth retardation or developmental delay was observed. The clinical findings for this case are summarised in Table 1.
Three-dimensional computed tomography (3D-CT) image of the patient. Mandibular condyle agenesis and excessively hypoplastic rami and processes can be observed. The possible positions of the mandibular jaw (white arrowhead) and process (red arrowhead) are indicated. The mandibular angle is unclear
We report a patient with severe mandibular hypoplasia, external ear malformation and a rounded face with prominent cheeks. Trio-based WES analysis revealed a novel missense variant of Gαi3, p.(Asn269Lys), which is predicted disruption of the hydrogen bond to the N7 atom of the guanine moiety. One patient with p.Asn269Tyr, which was different substitution to Tyr, was reported [6]. The N7 seems to be backbone of tryptophane, therefore hydrophobic interaction might be likely and easy disrupted by substitution of Lysine, supporting that mandibular hypoplasia phenotype in our patient (Supplementary Fig. 1) is more severe than in the patient with p.Asn269Tyr [6]. Her head 3D-CT showed agenesis of the mandibular condyle, retrognathia and an excessively short mandibular rami, which were fused with the medial and lateral pterygoid plates.
The development of the mandibula is uniquely regulated during embryogenesis and is also affected by postnatal food preference [15]. Dlx5/Dlx6 knockout mice show a hypoplastic mandibula similar to that found in ARCND [16]. Gnai3, Plcb4 and Edn1 act as upstream molecules in the endotherin-Dlx5/Dlx6 signalling pathway, and dysregulation of the pathway is involved in the pathogenicity of ARCND [2, 6, 17]. However, the mandibular hypoplasia of ARCND1 is much more severe than that of ARCND2 and ARCND3 (Table 1 and Supplementary Table S1). Another pathway may support such severity. It is interesting that both the mandibular condyle and the pterygoid process undergo cartilage and membrane ossification during their development and growth [18]. In mouse embryos, SRY-box 9 (Sox 9) was found to be first expressed in chondrocytes in the cranial base prior to expression of type X collagen at E14.5 and in chondrocytes of the condylar cartilage at E15.5 [18]. Both overexpression and knockout of Sox9 lead to dramatic inhibition of chondrocyte proliferation and terminal differentiation, which results in false endochondral-like ossification of these regions [19]. Sox9 is regulated by Gnai3 via PKA and cAMP [20]. Gαi3 variants could also affect the SOX9 expression during embryogenesis, possibly causing the severity.
La articulación de la mandíbula, también llamada articulación temporomandibular (ATM), es una articulación en forma de rótula similar a la del hombro. Los músculos alrededor controlan los movimientos, como abrir y cerrar la boca, masticar y bostezar.
Pensé en operarme años atrás cuando mis síntomas de TMD se agravaron un par de veces, pero aprendí a manejar el problema. He manejado mi TMD por más de 10 años ya no exigiendo la mandíbula, haciendo estiramientos mandibulares, usando una férula dental cuando estoy estresado y rechino los dientes por la noche, y usando medicamentos cuando los espasmos musculares se convierten en un problema. Nunca va a volver a estar "bien", pero tengo miedo de empeorarlo si me opero!
"Pensé en operarme años atrás cuando mis síntomas de TMD se agravaron un par de veces, pero aprendí a manejar el problema. He manejado mi TMD por más de 10 años ya no exigiendo la mandíbula, haciendo estiramientos mandibulares, usando una férula dental cuando estoy estresado y rechino los dientes por la noche, y usando medicamentos cuando los espasmos musculares se convierten en un problema. Nunca va a volver a estar "bien", pero tengo miedo de empeorarlo si me opero!"
A 10-year-old male was referred to the Bucco-Maxillo- Facial Surgery Department of Hospital Piñero for study of an increase in the volume of the right mandibular angle over a two-week period. He had no medical history of interest. The mass was not tender and there was no paresthesia (Fig. 1).
En la parte media de dicha cara, encontramos un orificio, que es el foramen mandibular u orificio de entrada al conducto dentario inferior, por donde ingresa al hueso el paquete vasculonervioso dentario inferior. Delante de este foramen encontramos una laminilla triangular llamada Espina de Spix, que es donde se inserta el ligamento esfenomandibular. De la parte inferior y posterior de esta cara encontramos un canal muy marcado denominado canal milohiodeo por donde recorren los nervios y vasos del mismo nombre. Igualmente encontramos en su parte inferior, diversas líneas de rugosidades donde se inserta el músculo pterigoideo interno. 041b061a72