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Rare genetic syndromes, conditions with a global average prevalence of 40 cases/100,000 people, are associated with anatomical, physiological, and neurological anomalies that may affect different body districts, including the oral district. So far, no classification of oral abnormalities in rare genetic syndromes is present in the literature. The aim of this narrative review is to analyze literature on rare genetic syndromes affecting dento-oro-maxillofacial structures (teeth, maxillary bones, oral soft tissues, or mixed) and to propose a classification according to the detected oral abnormalities. In addition, five significant cases of rare genetic syndromes are presented. The Scale for the Assessment of Narrative Review Articles (SANRA) was followed for this review. From 674 papers obtained through PubMed search, 351 were selected. Sixty-two rare genetic syndromes involving oral manifestations were found and classified. The proposed classification aims to help the clinician to easily understand which dento-oro-maxillofacial findings might be expected in the presence of each rare genetic syndrome. This immediate framework may both help in the diagnosis of dento-oro-maxillofacial anomalies related to the underlying pathology as well as facilitate the drafting of treatment plans with the involvement of a multidisciplinary team.

Light chain amyloidosis (AL) is caused by the aberrant overproduction of immunoglobulin light chains (LCs). The resulting abnormally high LC concentrations in blood lead to deposit formation in the heart and other target organs. Organ damage is caused not only by the accumulation of bulky amyloid deposits, but extensive clinical data indicate that circulating soluble LCs also exert cardiotoxic effects. The nematode C. elegans has been validated to recapitulate LC soluble toxicity in vivo, and in such a model a role for copper ions in increasing LC soluble toxicity has been reported. Here, we applied microscale thermophoresis, isothermal calorimetry and thermal melting to demonstrate the specific binding of Cu2+ to the variable domain of amyloidogenic H7 with a sub-micromolar affinity. Histidine residues present in the LC sequence are not involved in the binding, and yet their mutation to Ala reduces the soluble toxicity of H7. Copper ions bind to and destabilize the variable domains and induce a limited stabilization in this domain. In summary, the data reported here, elucidate the biochemical bases of the Cu2+-induced toxicity; moreover, they also show that copper binding is just one of the several biochemical traits contributing to LC soluble in vivo toxicity.

Aim: The clinical management of OLP represents a considerable challenge for the oral physician. The aim of this review is to assess the main intervention used in the management of OLP and the efficacy of every type of treatment. Materials & Methods: We searched and analyzed PubMed database for articles on OLP management. Only randomized controlled trials, comparing an active treatment with placebo, or between different active treatments, were considered in this systematic review. Only patients with symptomatic OLP were included and interventions of all types were considered (topical treatment, systemic drugs, non pharmacological intervention). Results: A total of 25 randomized controlled trials were examined and included in this review. Steroids are the most frequently employed drug in the treatment of OLP and their efficacy and safety are demonstrated. Also calcineurin inhibitors and photo-dynamic therapy are used in different studies for OLP management, with positive results. Conclusion: Topical steroids remain the first-line treatment for symptomatic OLP, however, many different pharmacological and non-pharmacological therapies would represent a valid alternative for its management, but, nowadays they require further investigations.

Herein, immunoglobulin light chains (LCs) native state was studied in the context of the pathology known as light chain amyloidosis (AL). This pathology is characterized by LCs overexpression, which leads to toxicity and aggregation into amyloid fibrils in target organs, with heart being the most affected one. Due to genetic rearrangement and somatic hypermutation, virtually, each AL patient presents a different amyloidogenic LC (Merlini, 2017). Because of such complexity, the fine molecular determinants of LC aggregation propensity and proteotoxicity are, to date, unclear; significantly, their decoding requires investigating large sets of cases. This project is aimed to unravel the molecular determinants linked with LCs toxicity. First, we screened several independent biophysical and structural properties of the LCs native state. In particular, we considered hydrophobicity, fold stability, flexibility and 3D structure. Our experimental approach considered two LCs sets called ?H? and ?M?. The H set is composed of eight LCs from AL patients while the M set by LCs from multiple myeloma (MM) patients. M LCs were chosen as control since they are overexpressed as the toxic H LCs but they do not lead to toxicity or aggregation. To date, the molecular bases leading to LC proteotoxicity remain to be elucidated. Our data show that low fold stability and high protein flexibility correlate with amyloidogenic LCs, while hydrophobicity, structural rearrangements and nature of the LC dimeric association interface (as observed in seven crystal structures here presented) do not appear to play a significant role in protein aggregation. Additionally, it has been demonstrated that the LCs toxicity in vivo is linked to copper (Cu2+) (Diomede et al., 2017a) by increasing the radical oxygen species (ROS) production. We aimed our studied to clarify Cu2+ LCs interaction. Moreover, we wanted to assess whether Cu2+ is able to alter the biophysical properties of the native state to more aggregation prone states. Our findings reveal that H LCs interacts with Cu2+ with a higher affinity than M LCs and that His residues may be involved in Cu2+ binding. Indeed the affinity decreases in presence of protonated His residues. Moreover, data suggest that the interaction with Cu2+ increases the molecular flexibility and decreases the fold stability. These observations suggests that protein aggregation cannot be evaluated through one single parameters but by the co-action of several biophysical traits. Moreover, our results suggest that the presence of Cu2+ can alter the native LCs properties leading to a higher toxicity in vivo.