Two novel variants in the ATM gene causing ataxia-telangiectasia, including a duplication of 90 kb: Utility of targeted next-generation sequencing in detection of copy number variation.

Ataxia-telangiectasia (A-T) is a rare autosomal recessive neurodegenerative disorder characterized by progressive cerebellar ataxia, ocular apraxia, immunodeficiency, telangiectasia, elevated serum α-fetoprotein concentration, radiosensitivity and cancer predisposition. Classical A-T is caused by biallelic variants on ATM (ataxia telangiectasia mutated) gene, leading to a loss of function of the protein kinase ATM, involved in DNA damage repair. Atypical presentations can be found in A-T-like disease or in Nijmegen breakage syndrome, caused by deficiency of mre11 or nibrin proteins, respectively. In this report, we present the genetic characterization of a 4-year-old female with clinical diagnosis of A-T. Next-generation sequencing (NGS) revealed two novel heterozygous mutations in the ATM gene: a single-nucleotide variant (SNV) at exon 47 (NM_000051.3:c.6899G > C; p.Trp2300Ser) and ∼90 kb genomic duplication spanning exons 17-61, NG_009830.1:g.(41245_49339)_(137044_147250)dup. These findings were validated by Sanger sequencing and MLPA (multiplex ligation-dependent probe amplification) analysis respectively. Familial segregation study confirmed that the two variants are inherited, and the infant is a compound heterozygote. Thus, our study expands the spectrum of ATM pathogenic variants and demonstrates the utility of targeted NGS in the detection of copy number variation.

Verrucous carcinoma of the oral mucosa: an epidemiological and follow-up study of patients treated with surgery in 5 last years.

INTRODUCTION: Oral Verrucous Carcinoma (OVC) is described apart of the Squamous Cell Carcinoma (SCC) due to its specific properties. The objective of our study is to show our series of cases of OVC and to compare with the SCC in terms of clinical manifestations, epidemiology, histopathology, treatment and follow-up. MATERIAL AND METHODS: This is a retrospective study of all the OVC treated in our department between January-2007 and December-2011. The analyzed variables were sex, age, localization in the oral cavity, histopathology, number of biopsies needed to diagnose OVC, TNM classification, treatment and recurrences during follow-up. RESULTS: Our sample was composed by n=14 patients, 57% female, with a mean age of 69.14 years. The most common localization was buccal mucosa (n=5). Seven patients were diagnosed of OVC with the first biopsy. TNM classification was: pT1: 7 patients, pT2: 3 patients, pT3: 3 patients, pT4: 1 patient. No cervical metastases were observed either in cervical neck dissection or during the follow-up of the patients. The treatment was surgery with clinical resection margins up to 1 cm in all cases, followed by radiotherapy in selected cases. Only n=1 patient (7.69%) presented a recurrence after 34 months of follow-up. The overall survival rate was 92.85%. CONCLUSIONS: In our population, OVC represents the 6.16% of all oral cavity and oropharynx cancer, and is more frequent in female patients above 70 years old. It uses to rise over a previous lesion, and usually affects the buccal mucosa. In patients with high suspicious lesions, more than one biopsy may be needed to diagnose OVC. No patient showed cervical dissemination. In our experience, treatment based on local resection, without cervical neck dissection, could be a good option for these patients.

Consensus Report and Recommendations on the Management of Late-stage Internal Derangement of the Temporomandibular Joint.

Introduction: This report investigates late-stage internal derangement (ID) of the temporomandibular joint (TMJ) with the aim of establishing a more effective and personalized treatment protocol to improve patients' quality of life (QoL). Material and methods: A consensus was reached among maxillofacial surgeons specializing in LSID, based on a literature research and collective expert experience following the Delphi method. Consensus was considered to be achieved when a response received at least 80% of votes. Results: Four expert groups were established, respectively, focusing on diagnosis, minimally invasive surgery (MIS), open surgery and joint replacement. A comprehensive approach to late-stage ID of the TMJ requires a consensus report. This underscores the need for a personalized treatment plan, considering the variability in clinical presentations and progression of this pathology. Our recommendations aim to optimize clinical outcomes and enhance patient QoL.

Needle tract seeding and malignant transformation of hepatocellular adenoma into well-differentiated hepatocellular carcinoma in a dog.

An 11-year-old neutered female Golden Retriever was referred for investigation of marked increases in liver enzyme activities. Abdominal ultrasound revealed a large pedunculated liver mass. Diagnosis of hepatocellular adenoma (HCA) was made when the mass was excised after a first unsuccessful attempt through ultrasound-guided core-needle biopsy. One and a half years after presentation, a nodule embedded between muscles of the abdominal wall appeared. The mass was first diagnosed as a well-differentiated hepatocellular carcinoma (HCC) through cytologic examination, which was later confirmed with histopathology. Ki 67 immunostaining of the abdominal wall nodule showed an increased immunoreactivity compared with the liver mass. Therefore, the present case documents the first needle-tract seeding of a hepatocellular epithelial tumor with possible malignant transformation of HCA into a well-differentiated HCC in a dog.

Molecular and Clinical Implications of Somatostatin Receptor Profile and Somatostatin Analogues Treatment in Oral Cavity Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) incidence has increased by 50% over the last decade. Unfortunately, surgery and adjuvant radiotherapy and chemotherapy are still the mainstream modality of treatment, underscoring the need for alternative therapies. Somatostatin-analogues (SSA) are efficacious and safe treatments for a variety of tumors, but the presence of somatostatin-receptors (SSTs) and pharmacological effects of SSA on OSCC are poorly known. In this study, we demonstrated that SST2 and SST3 levels were significantly higher in OSCC, compared to adjacent healthy control tissues. SST2 expression was associated with less regional metastasis and a lower recurrence rate. Moreover, SST2 was elevated in OSCC and associated with histopathological good prognosis factors, such as high peritumoral inflammation, smaller depth of invasion, and expansive vs. infiltrative front of tumor invasion. Importantly, treatment with different SSA (octreotide, lanreotide, and pasireotide) significantly reduced cell-proliferation in OSCC primary cell cultures. Altogether, this study demonstrated that SST2 is overexpressed in OSCC vs. healthy tissues and could represent a novel prognostic biomarker, since its expression is associated with tumors that show better prognostic factors and less recurrent rate. Moreover, our data unveil clear antitumoral effects of SSAs on OSCC, opening new avenues to explore their potential as targeting therapy to OSCC.

Burkitt's lymphoma: a child's case presenting in the maxilla. Clinical and radiological aspects.

Burkitt's lymphoma (BL) is a neoplasm which, despite its very aggressive behaviour is potentially curable. It typically affects the paediatric population. BL belongs to the non-Hodgkin lymphomas group, and is the first human tumour undoubtedly related to a viral origin (Epstein-Barr virus). Two main clinical subtypes are recognized: endemic or African type, and sporadic type; HIV associated BL constitutes a third type. Although common in endemic BL, maxillary involvement is rare in sporadic cases. This, together with the clinical lack of specificity associated to this location, makes diagnosis difficult. New chemotherapeutic protocols achieve a high survival rate. Most important prognostic factors are location and tumour stage. We report a paediatric case of BL presenting in the maxilla, with a review and a description of the characteristics of the disease.

Cyberbullying, Self-concept and Academic Goals in Childhood.

Cyberbullying has aroused scientific interest given the impact it has on the lives of young people. The present study proposes to analyze the relationship between self-concept (Self-Description Questionnaire I), academic goals (Achievement Goals Tendencies Questionnaire), and the participation of the roles of victim, bully and bystander in cyberbullying (Cyberbullying. Screening for peer bullying and cyberbullying), by gender and grade. The sample was composed of 548 students (49.8% girls) in 5th and 6th grade of Primary Education (Mage = 10.95, SD = 0.7). Logistic regression analyses showed the explicative role of social self-concept and learning goals in the three roles, highlighting the academic self-concept and achievement goals in the victims, as well as the high social reinforcement goals in bullies and bystanders. This relation varied slightly according to gender and grade, being the motivational orientation towards school achievement a protector of victimization in girls and 6th grade students. The findings are discussed, pointing out their involvement in the development of preventive cyberbullying programs in preadolescence.

Bilateral Parotid Sialadenosis Associated with Long-Standing Bulimia: A Case Report and Literature Review.

PURPOSE: Bulimia is a common cause of sialadenosis. This paper presents a case of bilateral parotid sialadenosis associated with long-standing bulimia, and reviews the relevant literature and current treatment options. METHODS AND RESULTS: A 32-year-old woman had severe bilateral parotid sialomegaly for the last 6 years, which had occurred secondary to bulimia nervosa, which she had since 14 years. Treatment with pilocarpine was unsuccessful, so she underwent bilateral conservative parotidectomy. This procedure not only improved the aesthetic appearance of the patient but also improved her social and work life and overall quality of life. CONCLUSIONS: Sialomegaly secondary to bulimia results in a major alteration of the aesthetics of a patient's face. Conservative measures are not enough in many cases, and parotidectomy may be the only viable option, as it can also significantly improve adherence to psychiatric treatment for bulimia, in addition to correcting the facial aesthetics.

Localized Leishmaniasis of the oral mucosa. A report of three cases.

The term leishmaniasis comprises a group of diseases caused by different species of a protozoon called Leishmania. Leishmaniasis is found worldwide, and is considered to be endemic in 88 countries. There are three main clinical forms of leishmaniasis: visceral leishmaniasis, cutaneous leishmaniasis and mucocutaneous leishmaniasis. Exclusive involvement of the mucosa is very rare. We present a series of three cases of mucosal leishmaniasis located in the oral cavity. The fact that all three cases were recorded in Spain (an area where L. infantum is endemic), suggests that the latter was the causal agent. The only manifestation of leishmaniasis disease in the described cases was the appearance of an oral lesion. Treatment was provided in the form of meglumine antimoniate in two patients, with a favorable response. One of the patients left the hospital after diagnosis, without receiving treatment, and the subsequent course is not known. A review is made of the literature on the subject.

Gingival neurofibroma in a neurofibromatosis type 1 patient.

Neurofibroma is a benign peripheral nerve sheath tumour. It is one of the most frequent tumours of neural origin and its presence is one of the clinical criteria for the diagnosis of type 1 neurofibromatosis (NF-I). Neurofibromatosis type 1 is an autosomal dominantly inherited disease due to an alteration in the long arm of chromosome 17. About 50% of NF-I patients have no family history of the disease. NF-I patients have skin lesions (cafe au lait spots and neurofibromas) as well as bone malformations and central nervous system tumours. Diagnosis is based on a series of clinical criteria. Gingival neurofibroma in NF-I is uncommon. Treatment of neurofibromas is surgical resection. The aim of this paper is to report a case of NF-I with gingival involvement and to review the literature.

Langerhans cell histiocytosis in the maxillofacial area in adults. Report of three cases.

Langerhans cell histiocytosis (LCH) is a disease of unknown etiology, characterized by proliferation of pathological Langerhans cells within different organs. It mainly affects children, but adult cases also occur, with an incidence rate of one to two per million. The head and neck are affected in almost 90% of cases. Diagnosis is made by means of histopathological analysis, and imaging studies are necessary in order to determine extent of the disease. There are no controlled trials proposing an optimal treatment protocol for LCH. Prognosis in adults is generally good due to the slow evolution of the disease and its favourable response to treatment. In our report, we present three cases of LCH in patients aged 16, 24, and 28 years respectively, with primary manifestation in the maxillofacial area. A literature review was also conducted.

Inflammatory pseudotumor of the parotid gland.

Inflammatory pseudotumor is a term that refers to a reactive pseudoneoplastic disorder that can appear in different locations of the human body. The lung is the most frequently affected organ. The etiology is still unknown. It affects individuals of both sexes and of a wide range of ages. The diagnosis is still difficult and it is based on the histological examination of the lesions composed of four cell-types: histiocytes, myofibroblasts, plasma cells and lymphocytes. With regard to the treatment regimes there is no agreement. Treatment ranges from surgical excision to radiotherapy, chemotherapy or steroids. The purpose of this article is to report one case of inflammatory pseudotumor located in the parotid gland and to make a special point of the difficulty in arriving at a correct diagnosis in order to achieve the most adequate treatment.

Spheno-orbital meningioma resection and reconstruction: the role of piezosurgery and premolded titanium mesh.

We present the clinical case of a patient with a spheno-orbital meningioma. Literature review of the treatment options, including the application of piezoelectric or ultrasound surgery and orbital reconstruction after meningioma resection, is also presented. Complete resection was performed by means of a frontotemporal craniotomy and an orbitozygomatic approach. Piezoelectric osteotomy was used around the optic nerve canal and the superior orbital fissure to minimize the damage to soft tissues. Orbital wall reconstruction was done using a titanium mesh previously premolded using a skull model. The superior orbital rim was reconstructed with calvarial bone grafts, and the sphenotemporal bone defect was covered with a titanium mesh cranioplasty. Ultrasonic vibrations to perform osteotomies in craniofacial surgery provide an interesting tool to reduce damage to surrounding soft tissues. Reconstruction of the roof and lateral orbital wall with premolded titanium meshes with a skull model is a safe and easy method to achieve a good orbital reconstruction and to avoid secondary sequelae.

Age predicts low-frequency transcranial magnetic stimulation efficacy in major depression.

BACKGROUND: Transcranial magnetic stimulation (TMS) effectiveness in major depression has so far been studied mainly with high-frequency (>1 Hz) administration (HF-TMS). However, some available studies with low-frequency TMS (LF-TMS) have provided similar response rates to HF-TMS with better tolerance, but the evidence is mixed and controversial. METHODS: Randomized, controlled, two arm, clinical trial. 34 Major Depression patients were randomly assigned to receive 20 sessions of real or sham TMS of the right dorsolateral prefrontal cortex as adjuvant treatment to pharmacotherapy. The main stimulation parameters were 20 trains at 110% of the motor threshold for 60 s at a frequency of 1 Hz. Blinded external evaluators administered the Hamilton Depression Rating Scale. RESULTS: Both treatment groups significantly improved, although there were no statistical differences between them. In the real TMS group patients age inversely correlated with improvement of depressive symptoms at the end of the study (r=-0683 p=0.002). The percentage of decrease in scores on the Hamilton Scale was greater in subjects younger than 45 years old vs. others (41.3 +/- 22.6 vs. 15.1 +/- 15.8; t=2.8 df=16, p=0.011). These real TMS subgroups did not differ significantly in their history of previous depressive disorders, or in the refractoriness indicators of the current episode. LIMITATIONS: Small size and highly refractory sample. CONCLUSION: Only younger patients benefited from LF-rTMS as adjuvant treatment to antidepressants in this study.

A naturalistic study of changes in pharmacological prescription for borderline personality disorder in clinical practice: from APA to NICE guidelines.

Although no psychotropic agents are specifically licensed for the management of borderline personality disorder (BPD), pharmacological treatment appears to be common. This study aimed to examine the drug prescriptions for patients with BPD in clinical practice, analyze the prescription patterns from the appearance of the American Psychiatric Association guidelines in 2001 until the National Institute for Health and Clinical Excellence guidelines in 2009, and identify the factors associated with such prescription of each type of drug. Naturalistic study on 226 consecutive BPD patients admitted to an outpatient BPD program. Socio-demographic, clinical and pharmacological treatment information was collected; factors associated with drug prescription were examined using logistic regression analyses for dichotomous outcomes measures. Changes in prescription patterns over time were also evaluated. Patients received an average of 2.7 drugs; only 6% were drug-free; 56% were taking ≥3 drugs and 30% ≥4 drugs. Over the past 8 years, prescription of antidepressants has remained stable; there has been a significant reduction in prescription of benzodiazepines and an increase in the use of mood stabilizers and atypical antipsychotics. Comorbidity with Axis I disorders was the main factor associated with drug prescription. Drug prescription and polypharmacy are common in the management of BPD in clinical practice.

Basal cell nevus syndrome: clinical and genetic diagnosis.

INTRODUCTION: Basal cell nevus syndrome (BCNS), also known as Gorlin-Goltz syndrome, comprises five main pathological features: nevoid basal cell carcinomas, keratocystic odontogenic tumors, congenital skeletal anomalies, calcification of the falx cerebri, and point skin depressions on the palms and/or soles. The disease exhibits a dominant autosomal hereditary trait, with implication of the human homologue of the Drosophila segment polarity Patched (PTCH) gene. BCNS is diagnosed on the basis of clinical and radiological criteria and can be confirmed by genetic study. The patient prognosis is very good, with normal life expectancy in most cases. METHODS: The present study reports two cases of BCNS with the presence of maxillo-mandibular keratocystic odontogenic tumors. RESULTS: One case was diagnosed according to clinical criteria, while the other required genetic confirmation that revealed a germ line mutation in exon 17 (c.2868delC), not previously described in the databases, which was considered to be responsible for the disease.