Periodontal (formerly type VIII) Ehlers-Danlos syndrome: Description of 13 novel cases and expansion of the clinical phenotype.

Periodontal Ehlers-Danlos syndrome (pEDS) is a rare condition caused by pathogenic variants in the C1R and C1S genes, encoding subunits C1r and C1s of the first component of the classical complement pathway. It is characterized by early-onset periodontitis with premature tooth loss, pretibial hyperpigmentation and skin fragility. Rare arterial complications have been reported, but venous insufficiency is rarely described. Here we report 13 novel patients carrying heterozygous pathogenic variants in C1R and C1S including three novel C1S variants (c.962G > C, c.961 T > G and c.961 T > A). In addition to the pEDS phenotype, three patients and one relative displayed widespread venous insufficiency leading to persistent varicose leg ulcers. One patient suffered an intracranial aneurysm with familial vascular complications including thoracic and abdominal aortic aneurysm and dissection and intracranial aneurysm rupture. This work confirms that vascular complications can occur, although they are not frequent, which leads us to propose to carry out a first complete non-invasive vascular evaluation at the time of the diagnosis in pEDS patients. However, larger case series are needed to improve our understanding of the link between complement pathway activation and connective tissue alterations observed in these patients, and to better assess the frequency, type and consequences of the vascular complications.

Impact of Molar Furcations on Photodynamic Therapy Outcomes: A 6-Month Split-Mouth Randomized Clinical Trial.

The effectiveness of adjunctive photodynamic treatment (PDT) to non-surgical periodontal therapy has been shown to depend on initial periodontal status. As molar furcation involvement impairs healing response to non-surgical periodontal therapy, the aim of this study was to evaluate the impact of furcation involvement on PDT outcomes. Thirty-six patients suffering from severe chronic periodontitis were included in a 6-month split-mouth randomized clinical trial. PDT applications used the toluidine blue O and a light-emitting diode (LED) with a red spectrum. Repeated PDT applications were performed in addition to non-surgical periodontal treatment at baseline and at 3-months. Pocket probing depth (PPD), plaque index, bleeding on probing, and clinical attachment level were recorded at baseline, and again at 3- and 6-months. Furcation sites of molars were compared to other sites of molars and non-molars. Multilevel analysis showed no PDT effect in molar furcation sites while an additional significant reduction (odds ratio = 0.67) of pockets with PPD > 5 mm in other sites at 3-months was measured. PPD reduction appeared delayed in molar furcation sites treated with PDT. There is no additional apparent benefit to use PDT in molar furcation sites for the reduction of pockets with PPD > 5 mm contrary to other sites.

Impact of tooth-related factors on photodynamic therapy effectiveness during active periodontal therapy: A 6-months split-mouth randomized clinical trial.

BACKGROUND: The persistence of periodontal pockets > 5 mm after periodontal treatments increases the risk of periodontitis recurrence and the need of periodontal surgery. This study evaluated the impact of tooth-related factors on the effectiveness of adjunctive photodynamic treatment (PDT) in the reduction of pockets > 5 mm during active periodontal treatment. METHODS: Thirty-six patients suffering from severe chronic periodontitis were evaluated in a 6-months split-mouth randomized clinical trial. Each quadrant was assigned to test (scaling and root planing (SRP) + PDT) or control (SRP alone) group. PDT was conducted using the toluidine blue O and a light-emitting diode (LED) with a red spectrum. PDT applications were performed immediately after SRP, 7 days later and at 3 months. Plaque index (PI), bleeding on probing (BOP), periodontal pocket depth (PPD), and clinical attachment level (CAL) were recorded at baseline, 3 and 6 months. RESULTS: Multilevel analysis showed a significant reduction of pockets > 5 mm in test group in comparison with control group at 3 (OR = 0.69) and 6 months (OR = 0.77). This effect was mainly observed at 6 months in initially deep sites (PPD > 6 mm) with BOP (OR = 0.57). At sites exhibiting PI > 1 no PDT effect was observed. A more moderate PDT effect was observed on mean PPD and BOP reductions at 3 months only. CONCLUSIONS: Repeated applications of PDT significantly improved SRP outcomes, reducing by more than 40% residual pockets > 5 mm in initially deep and bleeding on probing periodontal sites. PDT effect was negatively influenced by dental plaque accumulation.

A targeted next-generation sequencing assay for the molecular diagnosis of genetic disorders with orodental involvement.

BACKGROUND: Orodental diseases include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a genetic syndrome. Due to the vast number of genes implicated in these disorders, establishing a molecular diagnosis can be challenging. We aimed to develop a targeted next-generation sequencing (NGS) assay to diagnose mutations and potentially identify novel genes mutated in this group of disorders. METHODS: We designed an NGS gene panel that targets 585 known and candidate genes in orodental disease. We screened a cohort of 101 unrelated patients without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of Rare Diseases, Strasbourg, France, for a variety of orodental disorders including isolated and syndromic amelogenesis imperfecta (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and syndromic dentinogenesis imperfecta, isolated dentin dysplasia, otodental dysplasia and primary failure of tooth eruption. RESULTS: We discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated patients in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of patients with isolated AI (50 unrelated patients) and isolated STHAG (21 unrelated patients), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, COL17A1 mutations accounted for the majority of autosomal-dominant AI cases. CONCLUSIONS: We have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of orodental diseases. Furthermore, our panel will contribute to better understanding the contribution of these genes to orodental disease. TRIAL REGISTRATION NUMBERS: NCT01746121 and NCT02397824.