Novel mutations in LRP6 highlight the role of WNT signaling in tooth agenesis.

PURPOSE: We aimed to identify a novel genetic cause of tooth agenesis (TA) and/or orofacial clefting (OFC) by combining whole-exome sequencing (WES) and targeted resequencing in a large cohort of TA and OFC patients. METHODS: WES was performed in two unrelated patients: one with severe TA and OFC and another with severe TA only. After deleterious mutations were identified in a gene encoding low-density lipoprotein receptor-related protein 6 (LRP6), all its exons were resequenced with molecular inversion probes in 67 patients with TA, 1,072 patients with OFC, and 706 controls. RESULTS: We identified a frameshift (c.4594delG, p.Cys1532fs) and a canonical splice-site mutation (c.3398-2A>C, p.?) in LRP6, respectively, in the patient with TA and OFC and in the patient with severe TA only. The targeted resequencing showed significant enrichment of unique LRP6 variants in TA patients but not in nonsyndromic OFC patients. Of the five variants in patients with TA, two affected the canonical splice site and three were missense variants; all variants segregated with the dominant phenotype, and in one case the missense mutation occurred de novo. CONCLUSION: Mutations in LRP6 cause TA in humans.Genet Med 18 11, 1158-1162.

Maxillomandibular Reconstruction Using Insourced Virtual Surgical Planning and Homemade CAD/CAM: A Single-Center Evolution in 75 Patients.

BACKGROUND: Virtual surgical planning (VSP) and computer-aided design and manufacturing (CAD/CAM) of surgical guides and jigs have dramatically changed the predictability of bony reconstruction of the jaw. VSP craftsmanship can lead to precision and enables the surgeon to complement the donor bone osteotomies with bony resection of the jaw. In recent years, immediate dental rehabilitation has become an integral part of VSP. However, outsourced CAD/CAM technology is expensive and may not be an option for many institutions worldwide. METHODS: The authors present here a consecutive series of 75 maxillofacial reconstructions from 2015 to 2020. We established an insourced "in-house" protocol for VSP and "home-made" CAD/CAM for the reconstruction of maxilla-mandibular defects with fibula, iliac crest, and scapular angle flaps. All patient files were analyzed retrospectively, and relevant parameters influencing the reconstructive outcome were determined. RESULTS: The authors went from a fibula-based protocol toward the selection of optimal vascularized bone for immediate placement of osteointegrated implants. Bone flap survival was 94.7% after 4 months. The 3-year patient survival is 77.6%. The authors show the multiple steps required for the routine use of in-house CAD/CAM and report the related financial balance. CONCLUSIONS: Insourced VSP and CAD/CAM has evolved into a valuable strategy in maxillomandibular reconstruction that promotes accuracy and precision and allows for occlusion-based planning with quality-of-life and aesthetic outcomes as essential parts of the reconstruction even in high-level oral cancers. Further reductions in the hardware and software acquisition costs may lead to widespread implementation of this innovative technology. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Novel Multidisciplinary Salivary Gland Society (MSGS) Questionnaire: An International Consensus.

OBJECTIVES: First, establishment and validation of a novel questionnaire documenting the burden of xerostomia and sialadenitis symptoms, including quality of life. Second, to compare two versions regarding the answering scale (proposed developed answers Q3 vs. 0-10 visual analogue scale Q10) of our newly developed questionnaire, in order to evaluate their comprehension by patients and their reproducibility in time. STUDY DESIGN: The study is a systematic review regarding the evaluation of the existing questionnaire and a cohort study regarding the validation of our new MSGS questionnaire. MATERIALS AND METHODS: A Multidisciplinary Salivary Gland Society (MSGS) questionnaire consisting of 20 questions and two scoring systems was developed to quantify symptoms of dry mouth and sialadenitis. Validation of the questionnaire was carried out on 199 patients with salivary pathologies (digestive, nasal, or age-related xerostomia, post radiation therapy, post radioiodine therapy, Sjögren's syndrome, IgG4 disease, recurrent juvenile parotitis, stones, and strictures) and a control group of 66 healthy volunteers. The coherence of the questionnaire's items, its reliability to distinguish patients from healthy volunteers, its comparison with unstimulated sialometry, and the time to fill both versions were assessed. RESULTS: The novel MSGS questionnaire showed good internal coherence of the items, indicating its pertinence: the scale reliability coefficients amounted to a Cronbach's alpha of 0.92 for Q10 and 0.90 for Q3. The time to complete Q3 and Q10 amounted, respectively, to 5.23 min (±2.3 min) and 5.65 min (±2.64 min) for patients and to 3.94 min (±3.94 min) and 3.75 min (±2.11 min) for healthy volunteers. The difference between Q3 and Q10 was not significant. CONCLUSION: We present a novel self-administered questionnaire quantifying xerostomia and non-tumoral salivary gland pathologies. We recommend the use of the Q10 version, as its scale type is well known in the literature and it translation for international use will be more accurate. Laryngoscope, 132:322-331, 2022.