Metastatic gallbladder cancer presenting as numb chin syndrome: A case report and literature review.

Gallbladder cancer (GBC) is an uncommon malignancy that is highly aggressive in the advanced stages. However, it rarely metastasizes to the mandible. Numb chin syndrome (NCS) is a rare neurological manifestation associated with various underlying causes, including occult primary cancers and distant metastases. It is often considered to be a significant indicator of malignancy, and thorough investigation is essential in the presence of unclear etiology. The current study reported on the case of a 69-year-old Japanese woman who presented with numbness and mild pain in the lower lip and chin area for three months. No other systemic symptoms were observed. Immunocytochemical examination revealed the presence of an adenocarcinoma and TNM staging as per the Union for International Cancer Control and the American Joint Committee on Cancer guidelines confirmed stage IVb GBC. Comprehensive full-body positron emission tomography-computed tomography examination using 18F-fluoro-2-deoxy-D-glucose revealed additional bone and soft-tissue metastases. Palliative chemotherapy and radiation treatment were initiated based on the advanced stage of disease at the time of diagnosis. However, the patient succumbed to multiple organ failure six months later. The simultaneous occurrence of GBC, mandibular metastasis and NCS is rare and associated with poor prognosis. Despite the widespread nature of the disease, it can often manifest as non-specific oral symptoms without any systemic indications. The current study emphasizes the critical importance of timely confirmatory testing for accurate diagnosis and initiation of appropriate management for such complex conditions.

Odontogenic keratocyst in the mandibular condyle base region: A case report.

Odontogenic keratocysts (OKCs) often occur in the molars in the mandibular ramus; they often progress asymptomatically and are discovered only after widespread development. Some cases of OKC progress to the mandibular condyle; however, very few cases exist only in the condyle. To the best of our knowledge, in all of the previously reported cases, OKCs occurred in the mandibular ramus, which underwent resection. The present study reports the case of a 31-year-old man in whom an OKC (13x12x6 mm) occurred discretely in the base of the condyle, in which the condylar head was successfully preserved. The tumor was removed under general anesthesia using the approach of shaving the anterior surface of the mandible. The extraction cavity was managed using the packed open technique and with an obturator. Approximately 20 months post-operation, the patient remained recurrence-free. This report presents a rare case of an OKC in the mandibular condyle base region. Resection was performed under general anesthesia and the condylar process was successfully preserved.

miR-935 Inhibits Oral Squamous Cell Carcinoma and Targets Inositol Polyphosphate-4-phosphatase Type IA (INPP4A).

BACKGROUND/AIM: Oral squamous cell carcinoma (OSCC) is a common malignancy with poor prognosis. Therefore, novel therapeutic options are needed to improve prognosis of OSCC. Recently, microRNAs (miRs) have received increasing attention as a potential therapeutic tool for carcinomas. However, no definitive miR-based drugs for patients with OSCC have been reported to date. The aim of this study was to identify new miRs potentially involved in cellular processes associated with OSCC malignancy, which could lead to novel therapeutic strategies. MATERIALS AND METHODS: We identified miRs that are modulated in OSCC and possibly regulate OSCC malignancy, using miR microarray on OSCC cell lines. RESULTS: miR-935 and miR-509-3p were down-regulated in OSCC cell lines and patient tissues. When miR-935 was overexpressed in HSC-3-M3 cells, proliferation, migration, and invasion of the cell line was suppressed, whereas apoptosis was increased. Moreover, we showed that the gene inositol polyphosphate-4-phosphatase type I A (INPP4A) is a potential target whose expression is positively regulated by miR-935. CONCLUSION: miR-935 may function as a tumor suppressor by inhibiting OSCC malignancy via INPP4A induction. Therefore, miR-935 can be a new therapeutic candidate for OSCC treatment.

Quadruple Multiple Primary Malignancies: Early Detection of Second Primary Malignancy by Esophagogastroduodenoscopy/Colonoscopy Is Crucial for Patients with Classic Kaposi's Sarcoma.

Currently, Kaposi's sarcoma (KS) is treated following the recommendations of international guidelines. These guidelines recommend esophagogastroduodenoscopy/colonoscopy for detecting multicentric KS of visceral lesions. Second primary malignancies (SPMs) are also a common KS complication; however, information on their detection and treatment is unfortunately not yet indicated in these guidelines. This paper reports on an 86-year-old man who suffered from quadruple primary malignancies: skin classic KS with colon adenocarcinoma, oral squamous cell carcinoma (maxilla), and well-differentiated stomach adenocarcinoma. Gastric cancer was incidentally detected during esophagogastroduodenoscopy, which was performed to detect visceral KS. We suggest that esophagogastroduodenoscopy/colonoscopy be routinely performed during the follow-up of patients with KS. As SPMs are crucial complications in patients with KS, these malignancies should be detected as early as possible.

Thymoma appearing 9 years after the resection of squamous cell carcinoma of the lip: A case report of triple primary tumors and literature review.

The occurrence of second primary tumor (SPT)following malignancy treatment is common. In patients with head and neck (H&N) cancer, SPTs principally occur in the H&N region, lungs or esophagus. Therefore, patient follow-up after cancer treatment is important in order to detect recurrence, metastasis and new primary tumors. However, no standard guidelines on lifelong follow-up imaging are available. Herein, we report a patient who presented with three metachronous primary tumors-squamous cell carcinoma (SCC) of the tongue, SCC of the lip and type A thymoma. The third tumor was incidentally detected during follow-up using contrast-enhanced computed tomography (CT) 9 years following resection of the second tumor. To the best of our knowledge, this specific combination of metachronous tumors has not yet been reported. Based on the literature review, we observed that thymoma occurs following H&N cancer treatment. Therefore, to ensure that the presence of subsequent thymomas is not overlooked, we suggest regular lifelong follow-up using contrast-enhanced CT in patients who had previously been diagnosed with H&N cancer. The literature review revealed that thymomas occur in patients with H&N cancer and should be detected at the earliest convenience.

Triple primary cancer of the head and neck, skin and prostate: A case report and literature review.

Second primary cancer (SPC) is an important prognostic factor for patients with head and neck cancer (HNC); therefore, the association between the prognosis and development of SPC has been well-reported. The use of 2-[18F]-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) is valuable to examine cancer stage, evaluate treatment responses and investigate suspected relapses or metastases. In the present study, the case of a male patient who was diagnosed with three primary cancer types, including well to moderately differentiated squamous cell carcinoma (SCC) of the mandible, axillary cutaneous poorly differentiated SCC and prostate adenocarcinoma, was described. Among these, mandible cancer was the first diagnosed when the patient was 70 years of age. Synchronous skin and prostate cancer (PRC) types then developed 3 years later. To the best of our knowledge, this is the first report of the aforementioned combination of cancer types. Postoperative FDG-PET was not performed as no lesions of recurrence or metastases of mandible cancer were found. Three years later, the PRC was asymptomatic and was incidentally detected by FDG-PET performed for a preoperative evaluation of skin cancer. It was indicated that FDG-PET could be utilized in patients with HNC due to there being no accurate FDG-PET protocol to detect SPC over a long-term follow-up.

Triple primary malignancies of surface osteosarcoma of jaw, myelodysplastic syndrome and colorectal cancer as a second primary cancer detected by PET2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography: A case report.

Second primary malignancy (SPM) is a severe issue for cancer survivors, particularly for osteosarcoma (OS) survivors. To date, the associations between subsequent SPM and OS have been well reported. Hematogenic and solid malignancies tend to occur following OS treatment. Reportedly, 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) is mainly used in OS patients for initial cancer staging, to evaluate the response of neoadjuvant chemotherapy, and when recurrence or metastasis is clinically suspected. The present case report describes a 70-year-old man diagnosed with three primary malignancies: jaw OS, myelodysplastic syndrome and colorectal adenocarcinoma. To the best of our knowledge, this combination of malignancies has not been reported previously. Until now, there is no specific protocol of postoperative FDG-PET for OS patients. Few studies have described OS follow-up methods; therefore, there is no consensus on proper follow-up methods. In the present case report, the colorectal early-stage SPM was observed, without any symptoms, by FDG-PET/computed tomography. To avoid overlooking solid SPMs, it is suggested that FDG-PET should be performed in the long-term follow-up of OS patients.

Dedifferentiated liposarcoma of the oral floor: A case study and literature review of 50 cases of head and neck neoplasm.

Dedifferentiated liposarcoma (DDLS) has a relatively poor prognosis, however this neoplasm rarely occurs in the head and neck. To date, no definite protocol has been established for the diagnosis and treatment of head and neck DDLS. The present study reports the case of a 69-year-old male patient with DDLS of the oral floor. To the best of our knowledge, this is the first documented case of oral floor DDLS. In addition, this is the first reported case with the development of a second primary malignancy following the treatment of head and neck DDLS. A literature review of 50 cases of head and neck DDLS revealed that preoperative biopsy is not reliable for the diagnosis of these tumors and an accurate pathological diagnosis with total resection is preferred.

MicroRNA-196a-5p is a potential prognostic marker of delayed lymph node metastasis in early-stage tongue squamous cell carcinoma.

MicroRNAs (miRs) are expected to serve as prognostic tools for cancer. However, many miRs have been reported as prognostic markers of recurrence or metastasis in oral squamous cell carcinoma patients. We aimed to determine the prognostic markers in early-stage tongue squamous cell carcinoma (TSCC). Based on previous studies, we hypothesized that miR-10a, 10b, 196a-5p, 196a-3p, and 196b were prognostic markers and we retrospectively performed miR expression analyses using formalin-fixed paraffin-embedded sections of surgical specimens. Total RNA was isolated from cancer tissues and adjacent normal tissue as control, and samples were collected by laser-capture microdissection. After cDNA synthesis, reverse transcription-quantitative polymerase chain reaction was performed. Statistical analyses for patient clinicopathological characteristics, recurrence/metastasis, and survival rates were performed to discern their relationships with miR expression levels, and the 2-ΔΔCq method was used. miR-196a-5p levels were significantly upregulated in early-stage TSCC, particularly in the lymph node metastasis (LNM) group. The LNM-free survival rate in the low miR-196a-5p ΔΔCq value regulation group was found to be lower than that in the high ΔΔCq value regulation group (P=0.0079). Receiver operating characteristic analysis of ΔΔCq values revealed that miR-196a-5p had a P-value=0.0025, area under the curve=0.740, and a cut-off value=-0.875 for distinguishing LNM. To our knowledge, this is the first study to examine LNM-related miRs in early-stage TSCC as well as miRs and 'delayed LNM' in head and neck cancer. miR-196a-5p upregulation may predict delayed LNM. Our data serve as a foundation for future studies to evaluate miR levels and facilitate the prediction of delayed LNM during early-stage TSCC, which prevent metastasis when combined with close follow-up and aggressive adjuvant therapy or elective neck dissection. Moreover, our data will serve as a foundation for future studies to evaluate whether miR-196a-5p can serve as a therapeutic marker for preventing metastasis.

Outcomes of an international volunteer surgical project for patients with cleft lip and/or cleft palate: A mission in developing Laos.

Cleft lip and/or palate (CL/P) is a common birth defect of complex etiology. CL/P surgery is generally performed in infancy to allow for improvements in esthetics, suckling, and speech disorders as quickly as possible. We have engaged in activities such as free-of-charge surgery for CL/P a total of 12 times from 2001 to 2016 in Lao People's Democratic Republic (Laos). The United Nations has designated Laos as a Least Developed Country; it is one of the poorest countries in Asia. We have carried out our activities for a long time, primarily in CL/P patients who cannot undergo surgery for financial reasons, and we have performed CL/P-related surgeries for 283 patients up to 2016. When we began our activities in 2001, the mean age at first cheiloplasty was 11.6 years, which dropped over time until 2016 when the mean age was 1.8 years. A linear regression analysis showed a significant difference between the age at first lip plasty and the year of first operation (ß = -0.35; P < 0.001). This was likely an effect of continuing to train local medical staff in surgical techniques and donating surgical tools and facilities over a period of 16 years while building a good relationship with local staff. However, the healthcare system in Laos is an obstacle to some patients who still cannot undergo CL/P surgery in infancy for financial reasons. We therefore need to support Laos to provide treatment on their own as we continue to carry out our activities for CL/P patients.

Kikuchi-Fujimoto disease in the regional lymph nodes with node metastasis in a patient with tongue cancer: A case report and literature review.

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare self-limiting disorder typically affecting the cervical lymph nodes (LNs), which is often misdiagnosed as other LN-associated diseases. KFD frequently presents with necrotic lesions and recurrences, which are also features of metastatic LNs. Clinicians may thus suspect LN metastasis when they encounter ipsilateral cervical lymphadenopathy in a patient with head and neck cancer. The present study reports the case of a 48-year-old man with tongue cancer and KFD affecting the right edge of his tongue and ipsilateral cervical LNs. LN metastasis was initially suspected, but pathological examination of the dissected LNs revealed one necrotic metastatic lesion and two necrotic KFD lesions. Ipsilateral cervical lymphadenopathy recurred 6 years after the initial surgery, and it was not possible to differentiate clinically between a second primary tumor and recurrent KFD prior to treatment. To the best of our knowledge, this is the first reported case of simultaneous tongue cancer, regional LN metastasis and KFD. This highlights the requirement to consider KFD in the event of LNs with necrotic lesions but no cancerous cells. A combination of clinical and pathological approaches may aid in the diagnosis of KFD, in addition to ruling out LN metastasis in initial and recurrent lymphadenopathies. The present study indicate that a diagnosis of KFD should be considered in patients with head and neck cancer that exhibit necrotic LNs lacking cancerous cells. This is important, as misdiagnosis of KFD as LN metastasis may lead to unnecessary adjuvant therapy.

Indolent growth of low-grade myofibroblastic sarcoma of the cheek mimics benign lesions: A case report and literature review.

Low-grade myofibroblastic sarcoma (LGMS) is a neoplasm of the soft tissue characterized by myofibroblastic differentiation. This type of tumor has been observed in various sites in the whole body, but frequently occurs in the head and neck region. It typically presents as a slow-growing painless mass, which is often mistaken for a benign lesion due to its indolent growth; however, LGMS is a malignant neoplasm. In the present study, a 43-year-old female presented with a 14-mm LGMS lesion in the buccal subcutaneous tissues of the buccinator muscle. The patient had initially noticed the lesion 2-months prior to presenting at the hospital. Following biopsy, the tumor was surgically resected and no recurrence or metastasis was observed during a follow-up time of 2 years. To the best of our knowledge, this case is the first report of LGMS located in the buccal subcutaneous tissue of the buccinator muscle. The present study a literature review of 55 cases of this tumor type in the head and neck region was conducted, revealing that the indolent growth of these lesions may contribute to a delay in diagnosis. The average time between the onset of clinical symptoms and hospital admission is 3.9 months, and this form of tumor is frequently misdiagnosed as a benign lesion. Therefore, the present study suggests that an incisional biopsy may be performed to rule out LGMS when clinicians encounter patients with the aforementioned indolent lesions anywhere in the body. In addition, the avoidance of radiotherapy is recommended following resection of the LGMS tumor, as it may induce LGMS recurrence.

Topographic analysis of the maxillary premolars relative to the maxillary sinus and the alveolar bone using cone beam computed tomography.

OBJECTIVE: The purpose of the present study was to elucidate the anatomic characteristics of the maxillary premolars for the planning of dental treatment using cone beam computed tomography (CBCT). STUDY DESIGN: CBCT images were obtained for 150 maxillary premolars in 68 patients. The internal angle formed by the long axis of the maxillary premolars and the long axis of the alveolar bone was evaluated on the cross-sectional images. The vertical relationships between the maxillary premolars and the maxillary sinus were classified into 5 categories. The bone width and internal angle were compared among the images classified into the 5 categories. RESULTS: The internal angle was 25.5 ± 6.9° at the maxillary first premolars. The incidence of Type I in the maxillary first premolars was 46.7%. In the maxillary second premolars, the incidence of Type I (14.7%) was significantly lower than the total incidence of Types II, III, IV, and V (85.3%). Type I had the significantly largest internal angle (28.0 ± 7.7°) among all types for the maxillary first premolars. CONCLUSION: When considering dental treatment in the maxillary premolars, one should observe the inclination of the maxillary premolars to the alveolar bone as well as the position of the inferior wall of the maxillary sinus.

Examination of the early wound healing process under different wound dressing conditions.

OBJECTIVE: Various types of wound-healing dressings have been used to assist in the healing of surgical wounds. We analyzed the wound-healing process in an animal model using different existing wound dressings. STUDY DESIGN: Full-thickness defects were created using a biopsy punch on the backs of 7-week-old rats. The wounded areas were covered with NEOVEIL (polyglycolic acid [PGA]) or TERUDERMIS (collagen sponge [CS]) affixed using a rat jacket. The wound area, neo-epithelium length, and α-smooth muscle actin (α-SMA) expression were evaluated and compared among the control, PGA, and CS groups. RESULTS: The wound areas in the control group on days 4 and 7 were significantly smaller than those in the PGA and CS groups. The expression of α-SMA in granulation tissue peaked on day 4 for all groups. The expression of α-SMA in the control group on days 4 and 7 after injury was greater than in the PGA and CS groups. However, there was no significant difference in the expression of α-SMA between the PGA and CS groups. CONCLUSIONS: In this study, PGA and CS suppressed wound contracture and reduced expression of α-SMA in wound areas. However, PGA and CS did not affect the neo-epithelium length at the wound site.

Perceptual-Speech, Nasometric, and Cephalometric Results After Modified V-Y Palatoplasties With or Without Mucosal Graft.

OBJECTIVE: Although the goal of cleft palate (CP) repair is to achieve normal speech, no standard procedure ensures that patients' speech will be at the same level as speech in children without CP. In this study, postoperative speech outcomes following primary CP repair combined with or without a mucosal graft was analyzed in comparison with that of control subjects without CP. PARTICIPANTS: Eighty-two patients who underwent modified V-Y palatoplasty with a mucosal graft on the nasal side for symmetrical muscular reconstruction during 2006-2012 (MG group) and 109 patients who previously underwent modified V-Y palatoplasty without a mucosal graft (non-MG group) were enrolled in this study. Speech data on 37 Japanese subjects without CP were used as a control. MAIN OUTCOME MEASURES: Perceptual rating of resonance and nasal emission and nasometry were carried out for all participants. Furthermore, cephalometric analyses were performed to assess postoperative velopharyngeal morphology and velar movement. RESULTS: Normal resonance was achieved at a significantly higher rate (90.3% of patients) in the MG group than in the non-MG group (68.8%) (P < .01). The mean nasalance scores in the MG group were significantly lower (P < .01) and were almost at the same level as in controls. Cephalometric analyses revealed a greater velar length and velar elevation angle during phonation in the MG group (P < .01 and P < .05, respectively). CONCLUSIONS: Modified V-Y palatoplasty combined with a mucosal graft on the nasal side of the velum for symmetrical muscular reconstruction facilitates speech outcomes for children with cleft palate that are comparable with those for peers without CP.

Outcome following secondary autogenous bone grafting before and after canine eruption in patients with unilateral cleft lip and palate.

OBJECTIVE: To determine whether the long axis and eruption of the cleft-adjacent canine affect postoperative outcomes in secondary autogenous bone grafting (SABG). DESIGN: Retrospective longitudinal study. SETTING: Multidisciplinary long-term follow-up at Kagoshima University Hospital. SUBJECTS AND METHODS: Twenty-five patients with complete unilateral cleft lip and palate (11 male, 14 female) were compared between unerupted and erupted groups for canine developmental stage, canine angle, and vertical height at bone grafting at 1 year and more than 4 years after SABG. The interalveolar septal heights at 1 and more than 4 years were evaluated by orthopantomograms. RESULTS: All patients in both groups accomplished dental rehabilitation with orthodontic treatment alone without prosthetic appliances. Although the rate of an acceptable bone bridge tended to be lower in the unerupted group (62.5%) than in the erupted group (88.8%), the difference was not significant (P = .158). The canine angle at bone grafting was significantly different between acceptable (69.2° ± 12.2°) and poor cases (77.3° ± 6.2°) at more than 4 years in the unerupted group (P = .049). The acceptable bone bridge rate might reflect mechanical stress added by natural eruption and orthodontic force. CONCLUSIONS: We suggest that SABG should be planned in accordance with the canine angle, crown and root development, the eruption position of the cleft-adjacent canine, and the timing of added mechanical stress in the alveolar cleft, considering the bone formation in the alveolar cleft.

Short-term molding effects on the upper alveolar arch following unilateral cleft lip repair with/without nasal vestibular expansion.

Objective : To elucidate the various effects on maxillary growth following different procedures for vestibular expansion at the time of primary lip repair for unilateral cleft lip and palate (UCLP). Participants : Thirty patients with complete UCLP who underwent primary lip repair using a triangular-flap technique with nasal vestibular expansion (NVE; the NVE group) and 30 patients who underwent the same lip repair with closure of the nasal floor (non-NVE group) were enrolled in this study. Interventions : Serial dental casts on lip and palatal repair were scanned with a laser scanner. The three-dimensional coordinates of seven anatomical landmarks and their growth changes, the curvature radius rate between major/minor segments, and the collapse rates were compared between the two groups. Results : At the time of lip repair, the incisal point was located slightly anteriorly in the non-NVE group. At the time of palatal repair, the cleft edge of the alveolar process in the minor segment was located significantly anteriorly and laterally in the NVE group, showing the significantly forward change of the minor segment. The minor segment collapsed in the non-NVE group. The collapse rate of the NVE group (3.3%) was significantly lower than that of the non-NVE group (40.0%). Conclusions : NVE following simultaneous advancement of nasolabial components on the affected side at the time of primary lip repair for UCLP facilitates the forward molding of the maxilla, resulting in a more symmetrical alveolar arch form.

Changes in grafted autogenous bone during edgewise treatment in patients with unilateral cleft lip/palate or alveolus.

Objective : To examine the changes in autogenous bone from 6 to 12 months after alveolar bone grafting (ABG) (T1) through completion of edgewise treatment (T2). Design : Retrospective longitudinal study. Setting : Multidisciplinary long-term follow-up at Kagoshima University Hospital. Patients : Forty-three patients with unilateral cleft lip and palate or alveolus. Main Outcome Measures : At T1 and T2, the bone bridge and quantity of grafted bone were evaluated using the Chelsea scale and the ABG scale. The cleft-adjacent tooth angles before ABG and at T2, as well as the number of orthodontic space closures, were examined. Patients were classified as having either adequate (type A or C; adequate group) or poor bone bridges (type B, D, E, or F; poor group) by the assessment at T1. Results : At T1, the ABG scores for the cleft-adjacent central incisor side of patients in the adequate group were higher than those of patients in the poor group (P < .001). At T2, the adequate group had higher ABG scores for the cleft-adjacent central incisor side (P = .022) and the canine sides (P = .034). No significant differences in tooth angles or the number of orthodontic space closures were noted between the groups. Conclusions : These results suggest that the quantity of grafted bone in the cleft-adjacent central incisor at 6 to 12 months post-ABG may be an indicator of the quantity of grafted bone that will be present after edgewise treatment.

Features of lateral cephalograms associated with difficult laryngoscopy in Japanese children undergoing oral and maxillofacial surgery.

BACKGROUND: Difficult laryngoscopy and tracheal intubation are occasionally encountered in children with congenital anomalies or micrognathia. However, no study has elucidated anatomical etiology in relation to craniofacial development. METHODS: Two hundred ten patients aged 8 months-18 years were analyzed. We analyzed the lateral cephalograms of: (i) eight patients in whom laryngoscopy was anticipated as difficult before anesthesia and who were unable to be intubated by direct laryngoscopy and needed fiberoptic bronchoscopy (group A); (ii) 11 patients in whom laryngoscopy was anticipated as difficult before anesthesia but who were able to be intubated by direct laryngoscopy (group B); and (iii) 191 patients in whom laryngoscopy was anticipated as easy before anesthesia and was actually found to be easy (group C). Eight cephalometric parameters were measured and age-parameter relationships were plotted. Logistic regression analysis was performed to characterize group A children for each of the cephalometric variables. RESULTS: Apparently insufficient growth of the mandible was observed in the group A children. Furthermore, the group A children of aged <4 years had undeveloped maxilla, longer mandibular plane-hyoid distances (≥1.3 cm), and deeper depth of the oropharynx; those of aged ≥4 years showed increased inclination of the mandible (sella-nasion plane to mandibular plane angle of ≥46.5°). CONCLUSIONS: Difficult laryngoscopy and tracheal intubation are expected in children aged <4 years with lower-positioned hyoid bone caused by caudal larynx as well as undeveloped maxilla and mandible, and in those aged ≥4 years with increased inclination of the mandible as well as undeveloped mandible.