Matthieu Schmittbuhl’s research while affiliated with Université de Montréal and other places

Invasive cervical resorption (ICR) is a dental lesion starting in the cervical region and involving the loss of dental hard tissue as a result of odontoclastic action. Due to its localization and invasive pattern, this process represents a challenging clinical situation. When feasible, the major aim of an ICR treatment is to completely remove the pathologic tissue (specifically at the entry point of the lesion) and to seal the resulting defect, without compromising tooth rehabilitation. In this context, choosing how to access the resorptive lacuna is essential. Two main options have been described in the literature: an external approach, requiring the surgical exposure of the resorptive lacuna, and an internal approach, taking advantage of the endodontic access cavity. However, there are no guidelines that indicate which approach to choose for the treatment of an ICR. This article is based on four clinical cases. It aims to provide specific clinical and radiologic features that should be considered in order to take the most appropriate decision, when choosing between the internal and the external approaches. It is proposed to base the therapeutic strategy on the accessibility and the size of the portal of entry of the lesion. When the entry point is wide, its extension along the root must also be taken into account. Other important parameters are the circumferential and vertical extents of the lesion in the radicular dentin. Although it is not a determining factor, the pulpal involvement of the lesion can also be considered.

Systemic sclerosis (SSc) is a rare multisystem connective-tissue disorder characterized by the triad fibrosis, vasculopathy and immunity dysregulation. This chronic disease has a significant impact on the orofacial region that is involved in more than two-thirds of the cases. SSc patients can show a wide array of oral manifestations, which are usually associated with a severe impairment of the quality of life. They often present a decreased the salivary flow and a reduced mouth opening that contribute substantially to the worsening of the oral health status. Therefore, SSc patients require specific and multidisciplinary interventions that should be initiated as early as possible. The identification of specific radiological and clinical signs at the early stage will improve the management of such patients. This study reviews the wide spectrum of orofacial manifestations associated with systemic sclerosis and suggests clues for the oral management that remains challenging. This article is protected by copyright. All rights reserved.

Purpose To report the dento-craniofacial phenotype of a family affected by a WNT10A HED and to describe the implant-based oral rehabilitation of a patient presenting a severe oligodontia linked to this mutation. A molecular hypothesis concerning the involvement of Wnt-β-catenin pathway in implant osteointegration will be proposed. Material and methods Patients affected by a WNT10A mutation were included from a large group of HED patients. WNT10A gene was sequenced in second intention for patients negative for EDA-EDAR-EDARADD mutations. Dento-craniofacial phenotype was described based on clinical and radiological data. Results Severe oligodontia was observed in the patient affected by a compound heterozygous mutation of WNT10A gene. CT exams showed marked maxillary bone hypoplasia in the posterior areas with a sub-normal mandible Treatment consisted in the placement of 4 mandibular implants and in 2 implant-supported bridges. In the maxilla, an autogenous bone graft was indicated. The post-operative radiological follow-up showed partial bone resorption of the grafts, treated with ramus bone shaving and a membrane, followed by the placement of 4 maxillary implants. Conclusion Patients affected by WNT10A HED require multi-disciplinary dental diagnosis and treatment. A close post-operative radiological follow-up appears necessary given the biological functions of Wnt-β-catenin in bone repair.

The RSK2 gene is responsible for Coffin-Lowry syndrome, an X-linked dominant genetic disorder causing mental retardation, skeletal growth delays, with craniofacial and digital abnormalities typically associated with this syndrome. Craniofacial and dental anomalies encountered in this rare disease have been poorly characterized. We examined, using X-Ray microtomographic analysis, the variable craniofacial dysmorphism and dental anomalies present in Rsk2 knockout mice, a model of Coffin-Lowry syndrome, as well as in triple Rsk1,2,3 knockout mutants. We report Rsk mutation produces surpernumerary teeth midline/mesial to the first molar. This highly penetrant phenotype recapitulates more ancestral tooth structures lost with evolution. Most likely this leads to a reduction of the maxillary diastema. Abnormalities of molar shape were generally restricted to the mesial part of both upper and lower first molars (M1). Expression analysis of the four Rsk genes (Rsk1, 2, 3 and 4) was performed at various stages of odontogenesis in wild-type (WT) mice. Rsk2 is expressed in the mesenchymal, neural crest-derived compartment, correlating with proliferative areas of the developing teeth. This is consistent with RSK2 functioning in cell cycle control and growth regulation, functions potentially responsible for severe dental phenotypes. To uncover molecular pathways involved in the etiology of these defects, we performed a comparative transcriptomic (DNA microarray) analysis of mandibular wild-type versus Rsk2-/Y molars. We further demonstrated a misregulation of several critical genes, using a Rsk2 shRNA knock-down strategy in molar tooth germs cultured in vitro. This study reveals RSK2 regulates craniofacial development including tooth development and patterning via novel transcriptional targets.

Background/aims: Calcium homeostasis requires regulated cellular and interstitial systems interacting to modulate the activity and movement of this ion. Disruption of these systems in the kidney results in nephrocalcinosis and nephrolithiasis, important medical problems whose pathogenesis is incompletely understood. Methods: We investigated 25 patients from 16 families with unexplained nephrocalcinosis and characteristic dental defects (amelogenesis imperfecta, gingival hyperplasia, impaired tooth eruption). To identify the causative gene, we performed genome-wide linkage analysis, exome capture, next-generation sequencing, and Sanger sequencing. Results: All patients had bi-allelic FAM20A mutations segregating with the disease; 20 different mutations were identified. Conclusions: This autosomal recessive disorder, also known as enamel renal syndrome, of FAM20A causes nephrocalcinosis and amelogenesis imperfecta. We speculate that all individuals with biallelic FAM20A mutations will eventually show nephrocalcinosis.

Systemic sclerosis (SSc), a multisystem autoimmune disease characterized by widespread fibrosis, vascular alterations, autoimmunity, and inflammation, has effects on the hard and soft tissues of the orofacial region. The most common oral radiographic features correspond to widening of the periodontal ligament space and to mandibular resorption. In this report, cone-beam computerized tomography (CBCT) confirmed not only the well described periodontal features associated with SSc but also revealed previously undescribed calcifications within the periodontal ligament space of most maxillary teeth. Moreover, CBCT showed pulp calcifications in some incisors and premolars with these calcifications leading to root canal obliterations. Such manifestations (which could be linked to different major pathogenic features of SSc such as calcinosis, vasculopathy, and fibrosis) contribute to the phenotypic spectrum of the disease.

3D MIP reconstruction of the skull (a) and cephalometric analysis innorma lateralis(b) of patient 8 (6.7 years) (See Table 2). The names and definitions of the landmarks and measured euclidien distances and angles are given in Additional files 1 and 2. Observe the direction of vertical growth of the lower jaw (angle 9 FMA) and retrognathia (diminished angle 2 Facial depth) or skeletal class II (Angle 11 ANB) can be seen.

Cephalometric analysis in norma frontalisof patient 16 (16.5 years). Correspondence of landmarks and measurements are detailed in Additional files 1 and 2 respectively. Reported to age related standards, transversal craniofacial hypodevelopment is patent).

Definition of selected landmarks used in the cephalometric analysis in norma lateralis and frontalis.

Background Cockayne Syndrome CS (Type A – CSA; or CS Type I OMIM #216400) (Type B – CSB; or CS Type II OMIM #133540) is a rare autosomal recessive neurological disease caused by defects in DNA repair characterized by progressive cachectic dwarfism, progressive intellectual disability with cerebral leukodystrophy, microcephaly, progressive pigmentary retinopathy, sensorineural deafness photosensitivity and possibly orofacial and dental anomalies. Methods We studied the cranio-oro-facial status of a group of 17 CS patients from 15 families participating in the National Hospital Program for Clinical Research (PHRC) 2005 « Clinical and molecular study of Cockayne syndrome ». All patients were examined by two investigators using the Diagnosing Dental Defects Database (D[4]/phenodent) record form. Results Various oro-facial and dental anomalies were found: retrognathia; micrognathia; high- arched narrow palate; tooth crowding; hypodontia (missing permanent lateral incisor, second premolars or molars), screwdriver shaped incisors, microdontia, radiculomegaly, and enamel hypoplasia. Eruption was usually normal. Dental caries was associated with enamel defects, a high sugar/carbohydrate soft food diet, poor oral hygiene and dry mouth. Cephalometric analysis revealed mid-face hypoplasia, a small retroposed mandible and hypo-development of the skull. Conclusion CS patients may have associated oro-dental features, some of which may be more frequent in CS children – some of them being described for the first time in this paper (agenesis of second permanent molars and radiculomegaly). The high susceptibility to rampant caries is related to a combination of factors as well as enamel developmental defects. Specific attention to these anomalies may contribute to diagnosis and help plan management.