OMENS+ Classification Correlations Analysis of Craniofacial Microsomia in China: The Relationship Between Macrostomia and Mandibular Hypoplasia.

ABSTRACT: Macrostomia is arare congenital craniofacial deformity that influences the appearance and function of patients. In most cases, it coexists with craniomaxillofacial deformities such as craniofacial microsomia (CFM). This study aimed to analyze the relationship between macrostomia and mandibular hypoplasia so as to facilitate the early detection and diagnosis of children with CFM. It included 236 patients diagnosed with CFM. All underwent facial expression analysis, multi-angle photography, computed tomography, and three-dimensional reconstruction of soft and hard tissues. The clinical classification was performed according to OMENS+. Spearman (rank) correlation analysis was used to analyze the relationship between the severity of macrostomia (C1 and C2) and the degree of mandibular involvement (M1, M2a, M2b, and M3), and the correlation among the components of OMENS+. Of the 80 cases of macrostomia (34%) reported, 72 cases (90%) were C1 and 8 (10%) were C2. The analysis of OMENS+ revealed significant correlations among OMENS+ components. Also, a high correlation was observed between macrostomia (C) and hypoplasia of the mandible (M) ( P  = 0.002). Macrostomia was closely related to mandibular hypoplasia among children diagnosed with CFM. These results suggested that patients with macrostomia, who might also have craniofacial malformations caused by other first branchial arch anomalies, should be comprehensively physically examined for other syndromes.

Mutation screening of Chinese Treacher Collins syndrome patients identified novel TCOF1 mutations.

Treacher Collins syndrome (TCS) (OMIM 154500) is a rare congenital craniofacial disorder with an autosomal dominant manner of inheritance in most cases. To date, three pathogenic genes (TCOF1, POLR1D and POLR1C) have been identified. In this study, we conducted mutational analysis on Chinese TCS patients to reveal a mutational spectrum of known causative genes and show phenotype-genotype data to provide more information for gene counselling and future studies on the pathogenesis of TCS. Twenty-two TCS patients were recruited from two tertiary referral centres, and Sanger sequencing for the coding exons and exon-intron boundaries of TCOF1, POLR1D and POLR1C was performed. For patients without small variants, further copy number variations (CNVs) analysis was conducted using high-density SNP array platforms. The Sanger sequencing overall mutation detection rate was as high as 86.3% (19/22) for our cohort. Fifteen TCOF1 pathogenic variants, including ten novel mutations, were identified in nineteen patients. No causative mutations in POLR1D and POLR1C genes and no CNVs mutations were detected. A suspected autosomal dominant inheritance case that implies germinal mosaicism was described. Our study confirmed that TCOF1 was the main disease-causing gene for the Chinese TCS population and revealed its mutation spectrum. We also addressed the need for more studies of mosaicism in TCS cases, which could explain the mechanism of autosomal dominant inheritance in TCS cases and benefit the prevention of TCS.

[Experience of midfacial distraction osteogenesis in upper airway stenosis].

OBJECTIVE: To investigate the therapeutic effects of upper airway stenosis after Le Fort III osteotomy and midfacial distraction osteogenesis (DO). METHODS: Eleven cases (age, 5-16 yrs) with severe midface dysostosis complicated with exophthalmos, anterior crossbite and upper airway stenosis were treated by using Le Fort III osteotomy and midfacial DO from August 2000 to February 2007. The 3D reconstruction of the upper-airway from CT data was used to evaluate the upper airway volume before and after the operation. And meanwhile polysomnography was carried out to demonstrate the upper airway functional changes. RESULTS: There was a 64.3% mean increase [mean, (9.13 +/- 6.94) ml, P < 0.05] in upper airway volume in the 11 cases after the operations. It showed that there was significant improvements in the indexes of polysomnography after the operations, such as apnea and hypopnea index, average SaO2, minimum oxygen saturation and snore index. CONCLUSIONS: The Le Fort III osteotomy and midfacial distraction osteogenesis can efficiently relieve the symptoms of upper-airway stenosis in severe midfacial dysostosis.

[Clinical study on the therapeutic effects and mechanism of progesterone in the treatment for acute severe head injury].

OBJECTIVE: To evaluate the therapeutic effects of Progesterone (PG) on the patients with acute severe traumatic brain injury, and investigate it's neuroprotective mechanisms. METHODS: Fifth-six patients with acute severe traumatic head injury were divided randomly into two groups: 26 cases were treated with PG and 30 cases were control. Neurological outcome of the patients were assessed using Glasgow Coma Scale (GCS), Glasgow Outcome Scale (GOS), verbal and motor functions scale and Karnofsky Performance Scale (KPS). The serum concentrations of PG, TNF-alpha and 15-F(2t)-isoprostane were measured at day 1, 5 and 10 after trauma. RESULTS: In the two groups, There were no significant difference in the mortality, GCS of acute healing phase, GOS and verbal and motor functions at 10th days after treatment (P>0.05); After follow-up for 3 months, GOS, verbal functions and KPSin the PG treatment group were better than those in the control group (P<0.05); In addition, there was no difference of motor functions in the two groups (P>0.05). At 5th day after trauma, serum 15-F(2t)-isoprostane and TNF-alpha levels increased in the control group, but decreased at 10th day after trauma. Compared with the control group serum PG levels increased, serum 15-F(2t)-isoprostane and TNF-alpha levels reduced significantly in the PG treatment group at 5th and 10th day after injury (P<0.05). CONCLUSION: It indicated that successive early application of PG will benefit the patients with acute severe head injury by improving the recovery and reducing the disability, which may be related to its alleviating inflammatory and lipid peroxidation response.

[Surgical correction of craniofacial dysostosis with midface distraction osteogenesis].

OBJECTIVE: To investigate the effect of distraction osteogenesis on correction of craniofacial dysostosis. METHODS: Le Fort III osteotomy was applied through coronal route on patients with craniofacial dysostosis such as Crouzon and Apert syndrome. The procedures included disconnecting the skeletal midface from base of cranium, setting up a RED II distraction device, and directing the device bars. The distraction was started 5 days after the surgery, with a rate of 1 mm forward per day. When midface approaching the right position, i.e. a slightly over correction of occlusion was reached, stopped distraction and kept the device for 2 - 4 months. RESULTS: Eight cases completed all the therapy. The average blood lose was 300 ml and the average operation time was 3.5 hours. The midface had been moved averagely 9 mm forwardly and 1.5 mm downwards. The features had been improved obviously and the occlusion reached nearly normal. No serious complications occurred except for 1 case of seroma and 1 case of infection around pin on scalp. No recurrence was found in the 5 months of follow-up. CONCLUSIONS: Midface distraction osteogenesis is propitious to teenage or severe cases of craniofacial dysostosis.

Trifocal distraction osteogenesis for reconstruction of skull defect.

OBJECTIVE: To apply trifocal distraction osteogenesis in canine model of skull segmental defects and to provide reference for clinical treatment. METHODS: Six labrador dogs were selected in this study and divided into observation group and control group randomly. Each group contained 3 dogs. Skull segmental defects models were established by surgery, and dogs in bservation group received trifocal distraction osteogenesis treatment. Bone density was observed and compared between two groups during treatment. RESULTS: There were no significant difference in bone density between two groups on th 1st day (P>0.05). The bone density of observation group on the 30th day, and 60th day were higher than that of control group (P<0.01). CONCLUSIONS: Trifocal distraction osteogenesis has significant clinical effect, and it would be widely used in clinical treatment.

Aligning protein sequence and analysing substitution pattern using a class-specific matrix.

Aligning protein sequences using a score matrix has became a routine but valuable method in modern biological research. However, alignment in the 'twilight zone' remains an open issue. It is feasible and necessary to construct a new score matrix as more protein structures are resolved. Three structural class-specific score matrices (all-alpha, all-beta and alpha/beta) were constructed based on the structure alignment of low identity proteins of the corresponding structural classes. The class-specific score matrices were significantly better than a structure-derived matrix (HSDM) and three other generalized matrices (BLOSUM30, BLOSUM60 and Gonnet250) in alignment performance tests. The optimized gap penalties presented here also promote alignment performance. The results indicate that different protein classes have distinct amino acid substitution patterns, and an amino acid score matrix should be constructed based on different structural classes. The class-specific score matrices could also be used in profile construction to improve homology detection.

[Changes of different section area at different parts of upper-airway after Le Fort III osteotomy].

OBJECTIVE: To observe the therapeutic effects of Le Fort III osteotomy and midface distraction osteogenesis (DO) on the upper-airway narrow. METHODS: Since 2000, 11 cases (10 cases of Crouzon syndrome and 1 case of Apert syndrome) with severe midface deficiency were treated with Le Fort III osteotomy and midface DO. The section area of different parts of upper-airway were tested by computer assistants image measurement preoperatively and postoperatively. Some patients received sleep function monitoring. RESULTS: The face appearance and the function of upper-airway improved significantly after Le Fort III osteotomy and Midface DO. The section area at the level of posterior nasal spine and uvula increased obviously after treatment (P < 0.05), however the section area at the level of epiglottis and separation between airway and esophagus were not obviously enlarged (P > 0.05). CONCLUSIONS: Midface DO after Le Fort III osteotomy can effectively improve the upper-airway narrow, especially the upper part from uvula.

[Surgical correction of craniofacial dysostosis with midface distraction osteotogenesis].

OBJECTIVE: Correction of craniofacial dysostosis with midface distraction osteotogenesis. METHODS: Le Fort III osteotomy has been employed through coronal route on patients with midface craniofacial dysostosis such as Crouzon and Apert syndrome. Then a REDII distraction device was set up, and the device bars directed. The distraction begins 6.4 days after the surgery, with a rate of 1 mm per day. When midface approaching the right position, i.e. an slightly over correction of occlusion is reached, the distraction stops and the device is held for the next 2-4 months. RESULTS: There are 8 cases completed all the therapy with an average age of 11.9 years old. The midface had been moved averagely 9.7 mm forwards and 1.6 mm downwards. The features had been improved obviously and the occlusions reach nearly normal. The exophthalmos reduced from 20.3 mm to 11.9 mm. In cephalometry, SNA was averagely enlarged 9 degrees, and ANB enlarged 8.8 degrees. The snore during sleeping was also improved in 87.5% cases. No serious complication had occurred except minor one such as 1 case of seroma and 1 case of infection around pin on scalp. According to 5 months averagely follow-up, there is no recurrence in our list. CONCLUSIONS: Midface distraction osteotogenesis is propitious to teenage or severe cases of craniofacial dysostosis.

Aligning protein sequence and analysing substitution pattern using a class-specifi c matrix.

Aligning protein sequences using a score matrix has became a routine but valuable method in modern biological research. However, alignment in the ‘twilight zone’ remains an open issue. It is feasible and necessary to construct a new score matrix as more protein structures are resolved. Three structural class-specifi c score matrices (all-alpha, allbeta and alpha/beta) were constructed based on the structure alignment of low identity proteins of the corresponding structural classes. The class-specifi c score matrices were signifi cantly better than a structure-derived matrix (HSDM) and three other generalized matrices (BLOSUM30, BLOSUM60 and Gonnet250) in alignment performance tests. The optimized gap penalties presented here also promote alignment performance. The results indicate that different protein classes have distinct amino acid substitution patterns, and an amino acid score matrix should be constructed based on different structural classes. The class-specifi c score matrices could also be used in profi le construction to improve homology detection.