KBG Syndrome: Prospective Videoconferencing and Use of AI-driven Facial Phenotyping in 25 New Patients

Genetic variants in the gene Ankyrin Repeat Domain 11 (ANKRD11) and deletions in 16q24.3 are known to cause KBG syndrome, a rare syndrome associated with craniofacial, intellectual, and neurobehavioral anomalies. We report 25 unpublished individuals from 22 families, all with molecularly confirmed diagnoses of KBG syndrome. Twenty-one individuals have de novo variants, three have inherited variants, and one is inherited from a mother exhibiting low-level mosaicism. Of these variants, 20 are truncating (frameshift or nonsense), and five are missense. We created a novel protocol for collection and reporting of data, including prospectively interviewing these individuals and their families throughout eight countries via videoconferencing by a single clinician. Participants' medical records, including imaging, were reviewed, and data was uploaded to the Human Disease Gene website using Human Phenotype Ontology (HPO) terms. Photos of the participants were submitted to GestaltMatcher and Face2Gene (FDNA Inc, USA) for facial analysis, and we found similar facial phenotypes among the participants. Within our cohort, common traits included short stature, macrodontia, anteverted nares, wide nasal bridge, wide nasal base, thick eyebrows, synophrys and hypertelorism. Seventy-two percent of participants had gastrointestinal complaints and 80% had hearing loss. Three participants were started on growth hormone with positive results. Behavioral issues and global developmental delays were found in most participants. Neurologic abnormalities including seizures and/or EEG abnormalities were also very common (44%), suggesting that early detection and seizure prophylaxis could be an important point of intervention. Twenty-four percent were diagnosed with attention deficit hyperactivity disorder (ADHD) and 28% were diagnosed with autism spectrum disorder (ASD). Additionally, we have identified minimally reported symptoms, including recurrent sinus infections (16%) and previously unreported migraines (20%). Based on the videoconferencing and these data, we provide a set of recommendations regarding diagnostic and treatment approaches for KBG syndrome.

Late endodontic treatment of a tooth with extrusive dislocation and invasive cervical resorption: a clinical case report

This study aims to report the clinical case of a 16 years-old male patient, who attended a private office reporting that at an accident suffered at the age of 10 years-old, which caused extrusive dislocation in both teeth 11 and 21. At that time, the teeth were repositioned, without an adequate follow-up. Upon physical and radiographic examination, the following features were observed: presence of recurrent sinus tract on the vestibular surface, area of ​​external cervical resorption, and a periapical lesion on tooth 21. Endodontic treatments (necropulpectomy) were performed on teeth 11 and 21, with the placement of a root canal dressing of calcium hydroxide and subsequent root canal filling. In addition, soft tissue flap folding was performed to treat the resorption area and to seal it with glass ionomer cement. A 7 months follow-up radiograph shows stabilization in the process of the tooth resorption and remission of the periapical lesion. In conclusion, the endodontic treatment with intracanal medication, and the sealing of the resorption area were successful to preserve the traumatized tooth. In addition, it is noteworthy that following up with the patient after the trauma episode is essential to monitor the pulp vitality of the tooth involved.

Cocaine-Induced Midline Destructive Lesions (CIMDL): A Real Challenge in Diagnosis

The prolonged use of intranasal cocaine can destroy the nasal architecture with the erosion of the palate, turbinates, and ethmoid sinuses causing cocaine-induced midline lesions (CIMDL). The CIMDL display a clinical pattern mimicking variable diseases. The aim of this study was to highlight the difficulties in reaching a correct diagnosis through the evaluation of eight new cases. The diagnostic procedures followed in these patients included: detailed medical history, clinical and histological examination, computed tomography and magnetic resonance imaging, laboratory findings (complete blood count, sedimentation rate, antinuclear antibody test, rheumatoid factor, venereal disease research laboratory test, leishmaniasis and fungal serology, antineutrophil cytoplasmic antibodies ANCA test), and chest X-ray. All patients complained of epistaxis, halitosis, nasal scabs and obstruction, decreased sense of smell and/or taste, oro-nasal regurgitation of solids and liquids with recurrent sinus infections, and chronic facial pain. On clinical examination, all patients showed palate perforation with variable nasal structure involvement and presented a strong positivity for ANCA tests with a p-ANCA pattern. The followed protocol for the CIMDL diagnosis allowed for a relatively quick and conclusive diagnosis in all patients. A multidisciplinary approach is mandatory in the management of CIMDL, involving dental professionals, maxillofacial surgeons, and psychologists.

Chronic intracranial hypertension after cerebral venous and sinus thrombosis – frequency and risk factors

Background Cerebral venous sinus thrombosis (CVST) can infrequently lead to chronical intracranial hypertension (IH) due to the altered venous drainage. The aim of this study was to ascertain the risk of IH after CVST and to stratify underlying risk factors. Methods We performed a retrospective cohort analysis of all cases treated for acute CVST at our department between 2013 and 2019. IH was diagnosed at follow-up according to the modified Dandy criteria. CVST-patients with and without IH were descriptively compared conforming to available clinical and radiological data as well as outcomes. Results Our study included 102 patients with acute CVST. In 70 cases complete follow-up data was available (68.6%). Seven of these patients developed symptomatic intracranial hypertension (10%; N = 7, n = 70) within a median follow-up of 6 months. Four of these patients (57.1% (N = 4, n = 7) vs. 3.2% (N = 2, n = 63); p < 0.001) presented recurrent sinus thrombosis in the further course. There were no significant differences between patients with or without IH concerning gender, age, risk factors, occluded vessels and treatment for their CVST. However the presence of visual deterioration at initial admission was higher in patients who developed IH afterwards (57.1% (N = 4, n = 7) vs. 20.6% (N = 13, n = 63); p = 0.03). Patients with chronic IH after CVST showed significantly less likely recanalization of the occluded vessel on follow-up MRI (no recanalization in 28.6% (N = 2, n = 7) vs. 4.8% (N = 3, n = 63); p = 0.02). All patients with IH had a good outcome (mRS 0–2) at discharge and follow-up. Conclusion IH occurred in around 10% after CVST. Insufficient recanalization status may facilitate IH. Patients with visual disturbances seem to develop more likely IH afterwards. Patients who present IH after CVST may develop recurrent cerebral venous thrombosis.

Midline Nasal Tip Sinus

Introduction Congenital midline sinus over tip of nose is a rare clinical presentation. Accurate diagnosis should be done to rule out intracranial extension and to prevent recurrence. Appropriate surgical approach depends upon location, extent and degree of intracranial extension. Management entails complete surgical excision of sinus tract. We discuss a rare case, where external rhinoplasty approach was used for excising recurrent sinus and patient was disease free. Case Report A 29 year old male patient with midline nasal tip sinus presented in our institute with history of opening over tip of nose since childhood associated with recurrent episodes of discharge from opening. Our objective is to present clinic-radiological-pathological profile of congenital nasal sinus along with review of literature. Discussion Nasal dermoid is rare embryological anomaly of ectodermal and mesodermal origin. Radiological imaging should be considered to rule out any intracranial extension. Goal of management is complete surgical excision with meticulous pre-operative and surgical planning to avoid complications and recurrence. External rhinoplasty provides best surgical exposure and allows excision of sinus tract.

A234 CLINICAL, ENDOSCOPIC AND HISTOLOGICAL IMPROVEMENT IN COMMON VARIABLE IMMUNODEFICIENCY DISEASE ASSOCIATED ENTEROPATHY WITH VEDOLIZUMAB

Background Common variable immune deficiency (CVID) can be associated with autoimmune manifestations including enteric inflammation and diarrhea. Systemic immunosuppression used in patients with inflammatory bowel disease (IBD) may be associated with increased risk of infection in CVID. Aims We report a patient with CVID associated intestinal enteropathy who underwent clinical, endoscopic and histological improvement after treatment with vedolizumab (IgG1 monoclonal antibody to α4β7 integrin), as well as a concurrent systematic review (SR) of the literature. Methods Case report and systematic literature review. We searched EMBASE, Medline, Cochrane CENTRAL, clinialtrials.gov, and the International Clinical Trials Registry Platform without language restriction using key words to identify patients with CVID associated enteropathy treated with vedolizumab. Clinical, endoscopic and histological outcomes were extracted and safety data. Results A 32-year-old male presented with weight loss, anemia and hypoalbuminemia on a background of chronic diarrhea and recurrent sinus infections. Serology and genetic testing was not consistent with celiac disease. Pan-endoscopy showed complete villous atrophy in the duodenum and biopsies showed and intraepithelial lymphocytosis (IEL) in the duodenum and terminal ileum. CT abdomen showed pan-enteritis with extensive mesenteric lymphadenopathy which were reactive on lymph node excision, as well as bronchiectasis. Pneumococcal vaccination challenge to assess humoral response confirmed CVID. After suboptimal response with steroids and mercaptopurine, treatment was initiated with vedolizumab 300mg IV at weeks 0, 2, and 6, then 8 weekly. This led to normalization of stool frequency, weight gain as well as endoscopic and histological resolution within 6 months of treatment. The SR yielded 101 studies of which 3 case series were identified reporting a total of 7 patients with CVID. In 5 cases there was clinical improvement, 4 reported endoscopic improvement and 3 patients had histologic improvement. No safety concerns associated with vedolizumab were reported. Conclusions Vedolizumab, a selective leucocyte inhibitor to the gut, was able to induce either clinical, endoscopic or histological improvement in 8 published cases in the worldwide literature. Prospective studies are needed to determine whether this treatment could be included in the therapeutic armamentarium for this orphan indication. Funding Agencies None

473 Chloroma: an unusual case with extensive cardiac involvement detected by echocardiography

Introduction Chloroma, also known as myeloid sarcoma, is a localized extramedullary tumour composed of malignant cells of the myeloid cell line, most frequently occurring in myelogenous leukemia. Heart involvement is exceptional, only about 20 cases have been reported in the literature. Case presentation A 38-year-old woman presenting with fatigue and pre-syncope was admitted to the hospital. The patient had a history of acute myeloid leukaemia diagnosed 2017, treated with chemotherapy and transplanted with allogenic bone-marrow the same year, remaining thereafter in clinical remission. Initial electrocardiogram showed sinus bradycardia and recurrent sinus arrests and therefore a pacemaker was implanted. An echocardiogram was performed which revealed multiple infiltrative masses with involvement of the superior vena cava extending to the right atrium, atrial septum, left atrium, mitral valve and aortic root. Magnetic resonance imaging was done confirming the echocardiographic results and showing even involvement of pulmonary veins, coronary arteries and myocardial infiltration. Chemoradiation was administered with initial response, however, disease progression led to the patients´death. Conclusion To our knowledge, this is the first case describing a chloroma with extensive involvement of cardiac walls, vessels and valves. This case also illustrates the value of echocardiography as a tool for early detection of cardiac masses. Abstract 473 Figure. Echo with contrast

EVALUATE THE RESULTS OF REVISION SINUS SURGERY FOR RECURRENT SINUSITIS AFTER FUNCTIONAL ENDOSCOPY SINUS SUGERY IN ADULTS

Objectives: To clarify the causes and risk factors for recurrent sinusitis after FESS in order to contribute to reducing the proportion of revison sinus surgery. Materials and methods: Cross sectional and descriptive study with clinical intervention in 35 patients with recurrent sinusitis after FESS from 3/2014 to 6/2016. Results: The common risk factors related to recurrent sinusitis after FESS are: no follow up 52,7%, smoking 37,1%, GERD 28,65%, chemical fumes exposure 25,7%. Clinical findings during operation: nasosinus polyp 65,7%, blocked osteomeatal complex 97,1%, blocked maxillary ostium 97,1%, blocked frontal recess 68,6%, blocked sphenoid ostium 45,7%, ulcinate process remnant 31,4%, ethmoidal air cells remnant 48,6%. Surgical results according to functional symptoms after 3 months and 6 months: after 3 months: good 80% , fair 20%. After 6 months: good are 83,3%. Endoscopic sinus surgical results: after 3 months: good 71,4%, after 6 months: good 66,6% CT scan imaging shows clear sinuses: after 3 months good and 6 months are good at 57,1% and 44,4% respectively. Conclusions: Recurrent sinusitis when surgery to comprehensive evaluation. Proposed a complete surgical methods to help patients from recurrent sinus. Surgeons must complete surgical manipulation. Ensure all patient get built and reconstructted draining sinus. Make sure to follow for all patients after operation. Key words: recurrent sinusitis, FESS (Functional Endoscopy Sinus Sugery)

Symptomatic Long Pauses and Bradycardia due to Massive Multinodular Goiter

Sinus node dysfunction with symptomatic bradycardia or chronotropic incompetence is generally an indication for pacemaker implantation. However, in patients with symptomatic sinus bradycardia, the identification and treatment of underlying pathologies may avoid the need for permanent pacemaker implantation. We present a case of carotid sinus syndrome and severe obstructive sleep apnea due to a massive multinodular goiter in a patient who presented with recurrent sinus pauses and syncope. The patient was managed without pacemaker implantation but instead with thyroidectomy resulting in decompression of the carotid sinus and airway and resolution of bradycardic episodes.