A catalog of the genetic causes of hereditary angioedema in the Canary Islands (Spain).

Hereditary angioedema (HAE) is a rare disease where known causes involve C1 inhibitor dysfunction or dysregulation of the kinin cascade. The updated HAE management guidelines recommend performing genetic tests to reach a precise diagnosis. Unfortunately, genetic tests are still uncommon in the diagnosis routine. Here, we characterized for the first time the genetic causes of HAE in affected families from the Canary Islands (Spain). Whole-exome sequencing data was obtained from 41 affected patients and unaffected relatives from 29 unrelated families identified in the archipelago. The Hereditary Angioedema Database Annotation (HADA) tool was used for pathogenicity classification and causal variant prioritization among the genes known to cause HAE. Manual reclassification of prioritized variants was used in those families lacking known causal variants. We detected a total of eight different variants causing HAE in this patient series, affecting essentially SERPING1 and F12 genes, one of them being a novel SERPING1 variant (c.686-12A>G) with a predicted splicing effect which was reclassified as likely pathogenic in one family. Altogether, the diagnostic yield by assessing previously reported causal genes and considering variant reclassifications according to the American College of Medical Genetics guidelines reached 66.7% (95% Confidence Interval [CI]: 30.1-91.0) in families with more than one affected member and 10.0% (95% CI: 1.8-33.1) among cases without family information for the disease. Despite the genetic causes of many patients remain to be identified, our results reinforce the need of genetic tests as first-tier diagnostic tool in this disease, as recommended by the international WAO/EAACI guidelines for the management of HAE.

First Census of Patients with Hereditary Angioedema in the Canary Islands.

Hereditary angioedema (HAE) is a rare genetic condition whose main symptoms are recurrent swelling in the skin, mucosa, and internal organs. Recent studies suggested that the regulation of the inflammatory response and the complement cascade are two of the pathways significantly enriched in the Canary Islands, Spain. Here, we describe the first HAE patient series in this region. Forty-one patients (33 F, 8 M) and nine healthy relatives belonging to twenty-nine families were recruited for this study, obtaining their clinical and demographic features using a data collection form, as well as blood samples for biochemical analysis. The mean age of patients was 36.8 years (ranging from 4 to 72 years). Positive family history of HAE was reported in 13 patients (32.5%), and a mean diagnosis delay of 7.9 (±12.5) years was estimated, ranging from months to 50 years. Cutaneous edema was the most common symptom (53.6%), while airway symptoms was present in 11 patients. Prophylactic treatment was indicated for 23 patients, while 14 also require on-demand rescue treatment. We estimate a minimum prevalence of 1.25:100,000 for HAE due to C1-INH deficiency or dysfunction in the Canary Islands, which is higher than the estimates for mainland Spanish populations. HAE continues to be a disease poorly recognized by health care professionals due to its confusing symptoms, leading to longer diagnosis delay. Altogether, the evidence reinforces the need for a rapid and accurate diagnosis and precision medicine-based studies to improve the patient's quality of life.

Does the transversal screw design increase the risk of mechanical complications in dental implants? A finite elements analysis.

The transversal screw was introduced in order to overcome some disadvantages of the transocclusal screw. However, its mechanical risk has not been studied sufficiently. The main purpose of this research was to assess and compare stress distribution in the screws and abutment of a single-crown implant with transversal and transocclusal screw models. Two 3D models were assembled to analyse a single-implant-supported prosthesis with transversal and transocclusal screws embedded in the jawbone. The crown was subjected to a static load of value 300 N with different levels of inclination. The transversal screw model, with an axial load of 15°, was the one with lowest stress values in all its components. However, the stress was greater with more inclined loads when compared with the transocclusal model. The prosthetic transversal screw showed much less stress than the rest of the components for any load inclination. The transversal screw design is the option with the lowest risk of mechanical complications, both in the prosthetic screw and in the abutment screw, when applying forces of lower inclination. The more oblique forces favoured a better biomechanical environment in the abutment and its screw in the transocclusal screw model.

Mandibular Flexure and Peri-Implant Bone Stress Distribution on an Implant-Supported Fixed Full-Arch Mandibular Prosthesis: 3D Finite Element Analysis.

PURPOSE: The purpose of this study was to evaluate and compare the effect of three mandibular full-arch superstructures on the peri-implant bone stress distribution during mandibular flexure caused by mid-opening (27 mm) and protrusion mandibular movements. MATERIALS AND METHODS: Three-dimensional finite element models were created simulating six osseointegrated implants in the jawbone. One model simulated a 1-piece framework and the other simulated 2-piece and 3-piece frameworks. Muscle forces with definite direction and magnitude were exerted over areas of attachment to simulate multiple force vectors of masticatory muscles during mandibular protrusion and opening. RESULTS: During the movement of 27.5 mm jaw opening, the 1-piece and 3-piece superstructures showed the lowest values of bone stress around the mesial implants, gradually increasing towards the distal position. During the protrusion movement, bone stress increased compared to opening for any implant situation and for a divided or undivided framework. The 3-piece framework showed the highest values of peri-implant bone stress, regardless of the implant situation. CONCLUSIONS: The undivided framework provides the best biomechanical environment during mandibular protrusion and opening. Protrusion movement increases the peri-implant bone stress. The most mesial implants have the lowest biomechanical risk.

Effect of implant- and occlusal load location on stress distribution in Locator attachments of mandibular overdenture. A finite element study.

PURPOSE: The aim of this study is to evaluate and compare the stress distribution in Locator attachments in mandibular two-implant overdentures according to implant locations and different loading conditions. MATERIALS AND METHODS: Four three-dimensional finite element models were created, simulating two osseointegrated implants in the mandible to support two Locator attachments and an overdenture. The models simulated an overdenture with implants located in the position of the level of lateral incisors, canines, second premolars, and crossed implant. A 150 N vertical unilateral and bilateral load was applied at different locations and 40 N was also applied when combined with anterior load at the midline. Data for von Mises stresses in the abutment (matrix) of the attachment and the plastic insert (patrix) of the attachment were produced numerically, color-coded, and compared between the models for attachments and loading conditions. RESULTS: Regardless of the load, the greatest stress values were recorded in the overdenture attachments with implants at lateral incisor locations. In all models and load conditions, the attachment abutment (matrix) withstood a much greater stress than the insert plastic (patrix). Regardless of the model, when a unilateral load was applied, the load side Locator attachments recorded a much higher stress compared to the contralateral side. However, with load bilateral posterior alone or combined at midline load, the stress distribution was more symmetrical. The stress is distributed primarily in the occlusal and lateral surface of the insert plastic patrix and threadless area of the abutment (matrix). CONCLUSION: The overdenture model with lateral incisor level implants is the worst design in terms of biomechanical environment for the attachment components. The bilateral load in general favors a more uniform stress distribution in both attachments compared to a much greater stress registered with unilateral load in the load side attachments. Regardless of the implant positions and the occlusal load application site, the stress transferred to the insert plastic is much lower than that registered in the abutment.

Influence of Implant Positions and Occlusal Forces on Peri-Implant Bone Stress in Mandibular Two-Implant Overdentures: A 3-Dimensional Finite Element Analysis.

The aim of this study was to evaluate and compare the bone stress around implants in mandibular 2-implant overdentures depending on the implant location and different loading conditions. Four 3-dimensional finite element models simulating a mandibular 2-implant overdenture and a Locator attachment system were designed. The implants were located at the lateral incisor, canine, second premolar, and crossed-implant levels. A 150 N unilateral and bilateral vertical load of different location was applied, as was 40 N when combined with midline load. Data for von Mises stress were produced numerically, color coded, and compared between the models for peri-implant bone and loading conditions. With unilateral loading, in all 4 models much higher peri-implant bone stress values were recorded on the load side compared with the no-load side, while with bilateral occlusal loading, the stress distribution was similar on both sides. In all models, the posterior unilateral load showed the highest stress, which decreased as the load was applied more mesially. In general, the best biomechanical environment in the peri-implant bone was found in the model with implants at premolar level. In the crossed-implant model, the load side greatly altered the biomechanical environment. Overall, the overdenture with implants at second premolar level should be the chosen design, regardless of where the load is applied. The occlusal loading application site influences the bone stress around the implant. Bilateral occlusal loading distributes the peri-implant bone stress symmetrically, while unilateral loading increases it greatly on the load side, no matter where the implants are located.