Evidenza del coinvolgimento di geni nell'insorgenza delle schisi labio-palatine

The CL/P are the most common and easily recognizable craniofacial malformations with a complex etiology that requires the involvement of genetic and environmental components. The analysis of the genetic component shows more than 14 loci and genes involved in the onset of the disease. I’ve selected and investigated some of the possible candidate genes for CL/P. MYH14 gene, that maps on chromosome 19, on the OFC3 locus, and shows a strong homology with MYH9 gene. I’ve also investigated TP63 and MID1 genes, that are responsible respectively for EEC syndrome and Opitz syndrome, both of them presenting cleft. I’ve also decided to investigate JAG2 because TP63 product regulates the this gene, and both of them are component of the Notch signalling pathway. I’ve, also, studied the MKX and LMO4 genes. MKX is an important development regulator that is highly expressed in palatal mesenchyme, and map in the region responsible for Twirler mutation that cause cleft in mouse. LMO4 is necessary for neural tube development and cooperating with Grhl3, promotes cellular migration during morphogenetic events like “in utero” cleft healing. Low folate levels and high levels of homocysteine increase the risk of cleft, genes involved in their metabolism may be of interest in cleft occurrence. I’ve decided to investigate BHMT and CBS genes coding for enzymes involved in homocysteine metabolism. I’ve also investigated BHMT2 gene that maps close to BHMT and presents with him a 73% of homology. I’ve performed a linkage analysis using SNPs mapping in the genes and their boundaries, for each gene, for MKX and LMO4 I’ve also performed a sequencing analysis. My results for MID1 and CBS genes support the hypothesis of a possible role of these genes in cleft. I’ve found borderline association values for JAG2, MKX and LMO4 genes.

Application of augmented reality in craniofacial surgery: a feasibility study

Augmented Reality (AR) is a novel promising technology, which is gaining success in the medical field. A number of applications in surgery have been described, but few studies have been focusing on pediatric craniofacial surgery. In this research project, the Authors have been implementing a system for intraoperative surgical navigation by means of HoloLens 2 by Microsoft, applied to pediatric craniofacial surgery. The Authors tested the device in a preclinical setting first, and then moved to patients. The Authors assessed the accuracy of the HoloLens 2 by performing 36 procedures in vitro on a printed 3D model of a patient. In clinical setting, 10 patients were prospectively enrolled in the study. The virtual surgical planning was designed for each patient and uploaded onto the software which allows for the AR interface and the standard neurosurgical navigator. For each patient, the surgeon has been drawing osteotomy lines both under the guidance of HoloLens2 and of the neurosurgical navigator. The Author then checked the accuracy with calibrated CAD CAM cutting guides with different grooves, in order to assess the accuracy of the osteotomies performed. We tested levels of accuracy of ±1.5 mm and ±1mm . In the preclinical setting, the HoloLens 2 performed with levels of accuracy of 1.5 mm, whereas in the real setting, surgeons were able to trace the osteotomy lines under the AR guidance for an amount of 45% (0.4 SD) of the entire line, with an accuracy level of ±1.5 mm. This percentage lowers to 34% (0.4 SD) when assessing accuracy level of ±1 mm. The results of the same tasks for the standard navigator are 36% and 16%, for ±1.5 mm and ± 1 mm accuracy level, respectively. The Authors reported encouraging results both in the preclinical and the clinical setting.