Exploration of Novel Genetic Evidence and Clinical Significance Into Hemifacial Microsomia Pathogenesis.

The authors browsed through past genetic findings in hemifacial microsomia along with our previously identified mutations in ITGB4 and PDE4DIP from whole genome sequencing of hemifacial microsomia patients. Wondering whether these genes influence mandibular bone modeling by regulation on osteogenesis, the authors approached mechanisms of hemifacial microsomia through this investigation into gene knockdown effects in vitro. MC3T3E1 cells were divided into 5 groups: the negative control group without osteogenesis induction or siRNA, the positive control group with only osteogenesis induction, and 3 gene silenced groups with both osteogenesis induction and siRNA. Validation of transfection was through fluorescence microscopy and quantitative real-time Polymerase chain reaction on knockdown efficiency. Changes in expression levels of the 3 genes during osteogenesis and impact of Itgb4 and Pde4dip knockdown on osteogenesis were examined by quantitative real-time Polymerase chain reaction, alkaline phosphatase, and alizarin red staining. Elevation of osteogenic genes Alpl, Col1a1, Bglap, Spp1, and Runx2 verified successful osteogenesis. Both genes were upregulated under osteogenic induction, while they had different trends over time. Intracellular fluorophores under microscope validated successful transfection and si-m-Itgb4_003, si-m-Pde4dip_002 had satisfactory knockdown effects. During osteogenesis, Pde4dip knockdown enhanced Spp1 expression (1.95±0.13 folds, P =0.045). The authors speculated that these genes may have different involvements in osteogenesis. Stimulated expression of Spp1 by Pde4dip knockdown may suggest that Pde4dip inhibits osteogenesis.

Discrepancy in Mandibular Medullary Cavity on Different Sides: More Hints Towards Understanding Hemifacial Microsomia.

The authors attempt to approach hemifacial microsomia with macroscopic techniques and look for a link between clinical manifestations with pathogenesis. In this study, for the first time mandibular medullary cavities as essential parts of the mandible were intravitally measured based on the 3-dimensional models. A total of 153 patients were included. The 3-dimensional models of patients' mandibles were reconstructed and medullary cavity volumes (mm 3 ) were measured. The ratio of medullary cavity volume to mandible volume was calculated to determine the proportion of the marrow in the bone. Statistical significance was found in mandible volumes ( P <0.001) and medullary cavity volumes ( P <0.001) on different sides. Medullary cavity volumes were significantly related to mandible volumes on both sides (both P <0.001). Medullary cavity volumes on the nonaffected and affected side were both in correlation with age but in different degrees ( r =0.214, P =0.008 versus r =0.170, P =0.036). The ratios of medullary cavity volume and the mandible were significantly different ( P <0.001) on 2 sides. The volume ratio on the nonaffected side correlated to age while this correlation did not exist on the affected side ( r =0.195, P =0.016 versus r =0.129, P =0.112). A smaller medullary cavity found on the affected side could lead to a reduced amount of bone marrow cells and consequently reduced osteogenic and hematopoietic potential. This could result in abnormal bone formation on the affected side of mandible. Proportions of marrow in bone on the affected side irrelevant to patients' ages signify a poorer potential of expansion. This may explain a higher reluctancy of growth in affected mandibular sides.

Morphological and quantitative study of the inferior alveolar nerve canal in hemifacial microsomia.

This study aimed to probe into the anatomic course of inferior alveolar nerve canal (IANC) in hemifacial microsomia (HFM) on a large scale, morphological observations and further quantitative study were performed. Patients were classified by Pruzansky-Kaban classification. The anatomic course of IANC was analyzed morphologically with three-dimensional (3D) imaging software among 248 patients. Seven distances between fixed landmarks on both sides were measured for 236 patients. The differences between affected and unaffected sides were compared. Significant differences were found in the entrance (P < 0.001), route (P < 0.001), and exit (P < 0.05) of IANC in type IIb and III HFM. The higher the degree of mandibular deformity was, the higher the incidence of IANC variation was (P < 0.05). The distances in the horizontal aspect of IANC including from mandibular foramen to mental foramen (P < 0.05) and from mental foramen to gonion (P < 0.05) were significantly shorter on the affected side. Abnormalities of the anatomical course of IANC exist in patients with Pruzansky-Kaban type IIb and type III HFM. The reduction of IANC on the affected side in the horizontal distance is more obvious. Three-dimensional imaging assessment is recommended before surgery.

Efficacy of navigation system-assisted distraction osteogenesis for hemifacial microsomia based on artificial intelligence for 3 to 18 years old: study protocol for a randomized controlled single-blind trial.

BACKGROUND: Mandibular distraction osteogenesis (MDO) is a major part of the treatment for hemifacial microsomia patients. Due to the narrow surgical field of the intraoral approach, osteotomy accuracy is highly dependent on the surgeons' experience. Electromagnetic (EM) tracking systems can achieve satisfying accuracy to provide helpful real-time surgical navigation. Our research team developed an EM navigation system based on artificial intelligence, which has been justified in improving the accuracy of osteotomy in the MDO in animal experiments. This study aims to clarify the effect of the EM navigation system in improving the MDO accuracy for hemifacial microsomia patients. METHODS: This study is designed as a single-centered and randomized controlled trial. Altogether, 22 hemifacial microsomia patients are randomly assigned to the experiment and control groups. All patients receive three-dimensional CT scans and preoperative surgical plans. The EM navigation system will be set up for those in the experiment group, and the control group will undergo traditional surgery. The primary outcome is the surgical precision by comparing the osteotomy position of pre- and postoperative CT scan images through the Geomagic Control software. The secondary outcomes include mandibular symmetry (occlusal plane deviation angle, mandibular ramus height, and body length), pain scale, and complications. Other indications, such as the adverse events of the system and the satisfactory score from patients and their families, will be recorded. DISCUSSION: This small sample randomized controlled trial intends to explore the application of an EM navigation system in MDO for patients, which has been adopted in other surgeries such as orthognathic procedures. Because of the delicate structures of children and the narrow surgical view, accurate osteotomy and protection of nearby tissue from injury are essential for successful treatment. The EM navigation system based on artificial intelligence adopted in this trial is hypothesized to provide precise real-time navigation for surgeons and optimally improve patient outcomes, including function and aesthetic results. The results of this trial will extend the application of new navigation technology in pediatric plastic surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200061565. Registered on 29 June 2022.

Piezosurgery in hemifacial microsomia: a promising exemption from conventional peri-osteotomy suffering.

Introduction: Mandibular distraction osteogenesis, a recommended therapy for hemifacial microsomia, has brought much agony because of its traumatic procedures and peri-osteotomy complications. Our study aims to retrospectively compare piezoelectric osteotome with conventional reciprocal bone saw for hemifacial microsomia patients and validate its meliority in operability, surgical risks and patient outcomes. Methods: All patients included underwent osteotomies conducted by either piezosurgery or bone saw. Information of intraoperative blood loss, operation duration, postoperative pain and complications was collected from patient files, ward round inspections and follow-ups. Results: Among all 40 patients, 13 underwent piezo-osteotomy. Piezosurgery performed better than conventional reciprocal bone saw in decreasing intraoperative blood loss (p < 0.001) and operation duration (p = 0.030). No significant difference was found in hospitalization duration, total expenses or complication rates between two groups. There were positive relations between operation duration and intraoperative blood loss (p = 0.042), and between hospitalization duration and total expenses (p = 0.0096). Postoperative pain scores of both groups declined over time while the piezosurgery group had a statistically significant tendency (p = 0.006) to suffer less than the conventional group. Discussion: Piezosurgery diminishes intraoperative blood loss, operative duration, and postoperative pain, making an alternative to conventional osteotomes to mitigate patients' and families' peri-osteotomy sufferings, and a more humane solution to HFM.

Quantitative structural analysis of hemifacial microsomia mandibles in different age groups.

Introduction: This study aims to quantitively analyze mandibular ramus and body deformities, assessing the asymmetry and progression in different components. Methods: This is a retrospective study on hemifacial microsomia children. They were divided into mild/severe groups by Pruzansky-Kaban classification and into three age groups (<1 year,1-5 years, 6-12 years old). Linear and volumetric measurements of the ramus and the body were collected via their preoperative imaging data to compare between the different sides and severities, using independent and paired tests, respectively. The progression of asymmetry was assessed by changes in affected/contralateral ratios with age using multi-group comparisons. Results: Two hundred and ten unilateral cases were studied. Generally, the affected ramus and body were significantly smaller than those on the contralateral side. Linear measurements on the affected side were shorter in the severe group. Regarding affected/contralateral ratios, the body was less affected than the ramus. Progressively decreased affected/contralateral ratios of body length, dentate segment volume, and hemimandible volume were found. Discussion: There were asymmetries in mandibular ramus and body regions, which involved the ramus more. A significant contribution to progressive asymmetry from the body suggests treatment focus in this region.