Further Expanding the Mutational Spectrum of Gorlin Syndrome in Three Unrelated Families.

Introduction: Gorlin syndrome is a rare, autosomal dominant multi-systemic disorder with a predisposition to the development of cancers such as medulloblastoma and nevoid basal cell carcinoma. Heterozygous pathogenic variants in PTCH1 are responsible for 90% of Gorlin syndrome cases. Pathogenic variants in PTCH1 cause overstimulation of the sonic hedgehog signaling pathway, which plays a role in the development of embryonic structures and tumorigenesis. Clinical major and minor diagnostic criteria for Gorlin syndrome have been determined. Odontogenic keratocyst (OKC) is the most common reason for medical admission in Gorlin syndrome. In this article, it is aimed to draw attention to the fact that patients with Gorlin syndrome are not very rare in our country and the variability in phenotypic and dysmorphic findings may be a clue for the diagnosis. Methods: Exome sequencing was performed on the Illumina NextSeq550 System platform by using the Ion Ampliseq exome RDY kit for Illumina. Sanger sequencing was performed accordingly for the other affected individuals in both families. Results: In this study, the clinical and molecular findings of 9 Gorlin syndrome patients from three unrelated families are presented. Macrocephaly, calcification of falx cerebri, palmar-plantar pits, rib anomalies, and OKC were detected in decreasing order in more than half of the patients. A novel heterozygous frameshift PTCH1 variant in family 1, a nonsense previously reported PTCH1 variant in family 2, and a novel heterozygous splice-site PTCH1 variant in family 3 were detected. Conclusion: Gorlin syndrome should be kept in mind in patients presenting with macrocephaly, palmoplantar pits, and OKC history. Careful examination of all family members is essential in the timely diagnosis of other affected individuals with minor phenotypic findings.

Evaluation of clinical signs and magnetic resonance imaging findings in patients with temporomandibular disorders.

This study assessed the relationship between clinical symptoms and magnetic resonance imaging (MRI) findings in temporomandibular disorders (TMD). A total of 324 temporomandibular joints (TMJs) from 162 patients were included. The TMJs were divided into three groups based on disc positions on MRI: normal disc position, anterior disc displacement with reduction (ADDwR), and anterior disc displacement without reduction (ADDwoR). Clinical findings included TMJ pain, TMJ noise, and maximum mouth opening (MMO). The disc configuration, disc positions, condylar morphology, and joint effusion were evaluated in proton density-weighted and T2-weighted open and closed-mouth sagittal sections. Patients comprised 135 females and 27 males, with a mean age of 37.63 ± 13.86 years. The VAS score was significantly higher in ADDwoR than in ADDwR (p = 0.007). Condylar sclerosis (ß coefficient: 1.449, 95% confidence interval (CI): 0.505-2.393, p = 0.003) and condylar flattening (ß coefficient: 1.024, 95% CI: 0.209-1.840, p = 0.014) had higher VAS scores than the other MRI findings in multiple regression analyses. Limited mouth opening (MO) was independently associated with ADDwoR. ADDwoR had a higher risk of having limited MO than normal disc position (odds ratio: 5.268), while there were no associations between limited MO and other MRI findings. None of the MRI findings showed significant performance in predicting TMJ noise. The convex and folded disc configuration percentages, the frequencies of osteophyte formation, and grade 3 effusion were significantly higher in the ADDwoR group. More severe clinical symptoms and a higher degree of disc deformity, osteophyte formation, and high-grade effusion were shown to be associated with ADDwoR.

The effect of drug holiday before tooth extraction on the development of medication-related osteonecrosis of the jaw in cancer patients receiving intravenous bisphosphonates.

Objectives: Drug holidays are suggested to reduce the formation of osteonecrosis in patients under intravenous (IV) bisphosphonates (BPs) therapy. The objectives of this study are to evaluate the incidence of medication-related osteonecrosis of the jaw (MRONJ) following tooth extraction in cancer patients using IV BP, and to assess the effect of drug holiday on the development of MRONJ. Patients and. Methods: A manuel search of the patient folders of Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Hacettepe University was undertaken to identify cancer patients who used IV BPs and had at least one tooth extraction between 2012 and 2022. Patents' age, sex, systemic condition, the type of BP used, duration of BP used, number of tooth extraction, duration of drug holiday, localization of tooth extraction and incidence of MRONJ were recorded. Results: One hundred nine teeth were removed from 57 jaws in 51 patients. All tooth extractions were performed under perioperative antibiotic prophylaxis and with primary wound closure. The incidence of MRONJ was 5.3%. Stage 1 MRONJ developed in 3 patients (only one had a drug holiday). The median duration of drug holiday was 2 months. No significant difference between the patients with and without a drug holiday and MRONJ development was found (P=0.315). The mean age of patients developed MRONJ was 40.33±8.08 years. A statistically significant difference was found between age and MRONJ development (P=0.002). Conclusion: The effect of a short-term drug holiday on the development of MRONJ may be limited because BPs remain in bone tissue for a long time. Drug holidays should be applied with the approval of an oncologist with other preventive measurements.

Intraosseous Mucoepidermoid Carcinoma of the Mandible Detected as an Asymptomatic Swelling.

Intraosseous mucoepidermoid carcinoma (IMEC) is a rare neoplasm of the jawbones. Although hypotheses focused on the malignant transformation of the epithelial mucosa of odontogenic cysts or ectopic salivary gland tissue have been suggested, the etiology of the disease is still unclear. It is more frequent in middle-aged individuals, has a slight female predilection, and is more common in the mandible than in the maxilla. Cortical enlargement is the most common symptom, while some lesions are detected by coincidence on radiography. This paper reports an IMEC of the mandible of a 35-year-old female, possibly arising from the remains of an odontogenic cyst associated with an unerupted mandibular molar, which was operated in an external center 5 years ago before IMEC diagnosis.

Retrospective evaluation of pathologic fractures in medication related osteonecrosis of the jaw.

The aim of this study was to focus on the MRONJ-related pathologic fractures, their incidence, and to analyze possible causative factors for their occurrence. Pathologic fracture in patients suffering frm MRONJ were identified, examined in detail, and the patient characteristics were evaluated. In 116 patients (73 female and 43 male; mean age 62.08 ± 13.6 years), pathologic fracture incidence was found to be 4.31%. Zoledronic acid was the most commonly used anti-resorptive drug (77.8%). Median antiresorptive usage was 24 months. Five patients had pathologic fractures in the mandible. Four fracture patients had metastatic prostate cancer, and one had metastatic renal cell cancer. This case series study can provide clinical insight into which factors are associated with pathologic fractures. Cancer type, medical comorbidities, additive toxicity of the combination of antiresorptive and antiangiogenic drugs, specific pathogens, and dento-alveolar surgical procedures may be some of the important factors that need to be considered. Since MRONJ-related pathologic fracture management can be complicated, it may be good to focus on the causative factors and prevent occurrence with regular follow-up as often as possible in line with these factors.