Craniosynostosis (CS) is a congenital skeletal disease caused by premature fusion of one or more cranial sutures. According to whether accompanied by injuries in other organ systems besides craniofacial deformity, CS can be divided into syndromic craniosynostosis (SCS) and non-syndromes craniosynostosis (NSC), accounting for 85% and 15% respectively. Especially, SCS can lead to more serious clinical symptoms. The occurrence of CS is influenced by both environmental and genetic factors, including monogenic mutation, chromosome abnormality and gene polymorphism. Common related genes include FGFR1, FGFR2, FGFR3, TWIST1, MSX1, ERF, TCF12. Most of published genetic studies on CS are concentrated in the European population, showing different genetic pathogenesis between SCS and NSC. Studies on molecular genetics of CS is important in the clinical diagnosis, treatment and genetic counseling. We reviewed the research status and progress of the pathogenesis of CS through the development of CS, as well as the genetic studies of SCS and NSC.

Objective:To explore the common pathogenic gene mutation in non-syndromic craniosynostosis in Chinese population.Methods:Patients with non-syndromic craniosynostosis were recruited in Huashan Hospital Affiliated to Fudan University from March 2018 to December 2020. A clinical questionnaire was designed to collect the general information of the patients. The gene panel was designed by entering the keywords craniosynostosis and gene panel in PubMed, extracting all relevant literature from January 1995 to May 2017. The gene library was sequenced on the Illumina HiSeq X platform, and bioinformatic analysis and pathogenic analysis were performed.Results:A total of 237 literatures were reviewed in the PubMed and Ovid databases, and the total sample was 3375 patients, of which 1822 cases (54%) were detected with corresponding mutations, involving 21 pathogenic genes. Based on the mutation detection rate of not less than 0.4%, 12 genes were selected in the gene panel: FGFR2, TWIST1, FGFR3, EFNB1, FGFR1, SKI, POR, RAB23, TCF12, MSX2, SMAD3 and ERF. A total of 109 patients with non-syndromic craniosynostosis were recruited in this study, including 62 males and 47 females; the average age was 2.1 years old. All participants denied family history. The average age at childbearing of father was 28.3 years old and of mother was 26.7 years old. 14 different pathogenic/ probable pathogenic mutation loci were found in the gene sequences of 19 patients. The mutation rate was 17.4%. The 14 mutation varients were distributed in 5 genes (FGFR2, TWIST1 , TCF12, EFNB1 , and FGFR3) . The 14 mutations can be classified into 5 missense mutations, 3 nonsense mutations, 1 splice mutation, 1 frameshift mutation and 4 in-frame deletion mutations, 11 of which have not been reported. These 11 novel mutations were mainly concentrated in two genes, TWIST1 and TCF12. The mutation types included: 3 loss-of-function, 4 frameshift deletions, 3 missense mutations, and 1 frameshift insertion, of which 7 were de novo mutation.Conclusions:TWIST1 and TCF12 are common pathogenic genes in Chinese patients with non-syndromic craniosynostosis.

Objective:To explore the feasibility and safety of the prophylactic optic canal decompression in frontol-orbital fibrous dysplasia surgery by three-dimensional simulation design and computer assisted navigation.Methods:A retrospected study was conducted in Huashan Hospital affiliated to Fudan University.Patients with stable fronto-orbital fibrous dysplasia were recruited from January 2016 to June 2020. Preoperatively, three-dimensional simulation design was used to design the scope of resection. Then a subtotal resection of fibrous dysplasia lesion was performed by computer assisted navigation and reshaping of the orbit rim was achieved by preserving the fronto-orbital bandeau. Meanwhile, the intracanal and intraorbital parts of optic nerve canal decompression was performed. Follow-up of the pre-op and post-op difference of the frontal bulge point, the lateral forehead point and orbitofrontal point of the affected side, the degree of proptosis, visual acuity and fundus were analyzed by paired t test. Results:A total of 7 patients were recruited, including 2 males and 5 females, with an average age of 22.5 years. The average follow-up time was 11.4 months, and the difference in exophthalmos between the two sides improved from an average of (6.7±1.6) mm before operation to an average of(2.9±1.1) mm at 6 months after operation, which was statistically significant ( P<0.001). The difference between the pre-op and post-op of the frontal bulge point on the affected side also improved from (18.1±3.4) mm before surgery to (3.1±3.5)mm( P=0.001) immediately after surgery and (4.0±3.6) mm( P=0.001)at 6 months after surgery. The difference of lateral forehead point improved from(21.4±4.1) mm before surgery to (1.8±1.9) mm( P<0.001) immediately after surgery and (2.5±2.1) mm( P<0.001) at 6 months after surgery, and the difference of orbitofrontal point improved from(12.2±2.5) mm before surgery to (2.3±3.0) m( P=0.004) immediately after surgery and (2.7±2.9) mm( P=0.006) at 6 months after surgery. The average uncorrected visual acuity of the affected side before operation was 4.5, and it was 4.6 6 months after operation, with no statistical difference( P>0.05). Conclusions:Using 3D simulation to design the scope of resection and computer assisted navigation to decompress the optic canal in patients with stable fronto-orbital fibrous dysplasia, which can safely and effectively protect the optic nerve and accurately improve the frontal-orbital shape.

Objective:To explore the feasibility and safety of the prophylactic optic canal decompression in frontol-orbital fibrous dysplasia surgery by three-dimensional simulation design and computer assisted navigation.Methods:A retrospected study was conducted in Huashan Hospital affiliated to Fudan University.Patients with stable fronto-orbital fibrous dysplasia were recruited from January 2016 to June 2020. Preoperatively, three-dimensional simulation design was used to design the scope of resection. Then a subtotal resection of fibrous dysplasia lesion was performed by computer assisted navigation and reshaping of the orbit rim was achieved by preserving the fronto-orbital bandeau. Meanwhile, the intracanal and intraorbital parts of optic nerve canal decompression was performed. Follow-up of the pre-op and post-op difference of the frontal bulge point, the lateral forehead point and orbitofrontal point of the affected side, the degree of proptosis, visual acuity and fundus were analyzed by paired t test. Results:A total of 7 patients were recruited, including 2 males and 5 females, with an average age of 22.5 years. The average follow-up time was 11.4 months, and the difference in exophthalmos between the two sides improved from an average of (6.7±1.6) mm before operation to an average of(2.9±1.1) mm at 6 months after operation, which was statistically significant ( P<0.001). The difference between the pre-op and post-op of the frontal bulge point on the affected side also improved from (18.1±3.4) mm before surgery to (3.1±3.5)mm( P=0.001) immediately after surgery and (4.0±3.6) mm( P=0.001)at 6 months after surgery. The difference of lateral forehead point improved from(21.4±4.1) mm before surgery to (1.8±1.9) mm( P<0.001) immediately after surgery and (2.5±2.1) mm( P<0.001) at 6 months after surgery, and the difference of orbitofrontal point improved from(12.2±2.5) mm before surgery to (2.3±3.0) m( P=0.004) immediately after surgery and (2.7±2.9) mm( P=0.006) at 6 months after surgery. The average uncorrected visual acuity of the affected side before operation was 4.5, and it was 4.6 6 months after operation, with no statistical difference( P>0.05). Conclusions:Using 3D simulation to design the scope of resection and computer assisted navigation to decompress the optic canal in patients with stable fronto-orbital fibrous dysplasia, which can safely and effectively protect the optic nerve and accurately improve the frontal-orbital shape.

Objective:To explore the common pathogenic gene mutation in non-syndromic craniosynostosis in Chinese population.Methods:Patients with non-syndromic craniosynostosis were recruited in Huashan Hospital Affiliated to Fudan University from March 2018 to December 2020. A clinical questionnaire was designed to collect the general information of the patients. The gene panel was designed by entering the keywords craniosynostosis and gene panel in PubMed, extracting all relevant literature from January 1995 to May 2017. The gene library was sequenced on the Illumina HiSeq X platform, and bioinformatic analysis and pathogenic analysis were performed.Results:A total of 237 literatures were reviewed in the PubMed and Ovid databases, and the total sample was 3 375 patients, of which 1 822 cases (54%) were detected with corresponding mutations, involving 21 pathogenic genes. Based on the mutation detection rate of not less than 0.4%, 12 genes were selected in the gene panel: FGFR2, TWIST1, FGFR3, EFNB1, FGFR1, SKI, POR, RAB23, TCF12, MSX2, SMAD3 and ERF. A total of 109 patients with non-syndromic craniosynostosis were recruited in this study, including 62 males and 47 females; the average age was 2.1 years old. All participants denied family history. The average age at childbearing of father was 28.3 years old and of mother was 26.7 years old. Fourteen different pathogenic/probable pathogenic mutation loci were found in the gene sequences of 19 patients. The mutation rate was 17.4%(19/109). The 14 mutation varients were distributed in 5 genes (FGFR2, TWIST1, TCF12, EFNB1, and FGFR3). The 14 mutations can be classified into 5 missense mutations, 3 nonsense mutations, 1 splice mutation, 1 frameshift mutation and 4 in-frame deletion mutations, 11 of which have not been reported. These 11 novel mutations were mainly concentrated in two genes, TWIST1 and TCF12. The mutation types included: 3 loss-of-function, 4 frameshift deletions, 3 missense mutations, and 1 frameshift insertion, of which 7 were de novo mutation.Conclusions:TWIST1 and TCF12 are common pathogenic genes in Chinese patients with non-syndromic craniosynostosis.

Craniosynostosis (CS) is a congenital skeletal disease caused by premature fusion of one or more cranial sutures. According to whether accompanied by injuries in other organ systems besides craniofacial deformity, CS can be divided into syndromic craniosynostosis (SCS) and non-syndromes craniosynostosis (NSC), accounting for 85% and 15% respectively. Especially, SCS can lead to more serious clinical symptoms. The occurrence of CS is influenced by both environmental and genetic factors, including monogenic mutation, chromosome abnormality and gene polymorphism. Common related genes include FGFR1, FGFR2, FGFR3, TWIST1, MSX1, ERF, TCF12. Most of published genetic studies on CS are concentrated in the European population, showing different genetic pathogenesis between SCS and NSC. Studies on molecular genetics of CS is important in the clinical diagnosis, treatment and genetic counseling. We reviewed the research status and progress of the pathogenesis of CS through the development of CS, as well as the genetic studies of SCS and NSC.

Objective:To explore the common pathogenic gene mutation in non-syndromic craniosynostosis in Chinese population.Methods:Patients with non-syndromic craniosynostosis were recruited in Huashan Hospital Affiliated to Fudan University from March 2018 to December 2020. A clinical questionnaire was designed to collect the general information of the patients. The gene panel was designed by entering the keywords craniosynostosis and gene panel in PubMed, extracting all relevant literature from January 1995 to May 2017. The gene library was sequenced on the Illumina HiSeq X platform, and bioinformatic analysis and pathogenic analysis were performed.Results:A total of 237 literatures were reviewed in the PubMed and Ovid databases, and the total sample was 3375 patients, of which 1822 cases (54%) were detected with corresponding mutations, involving 21 pathogenic genes. Based on the mutation detection rate of not less than 0.4%, 12 genes were selected in the gene panel: FGFR2, TWIST1, FGFR3, EFNB1, FGFR1, SKI, POR, RAB23, TCF12, MSX2, SMAD3 and ERF. A total of 109 patients with non-syndromic craniosynostosis were recruited in this study, including 62 males and 47 females; the average age was 2.1 years old. All participants denied family history. The average age at childbearing of father was 28.3 years old and of mother was 26.7 years old. 14 different pathogenic/ probable pathogenic mutation loci were found in the gene sequences of 19 patients. The mutation rate was 17.4%. The 14 mutation varients were distributed in 5 genes (FGFR2, TWIST1 , TCF12, EFNB1 , and FGFR3) . The 14 mutations can be classified into 5 missense mutations, 3 nonsense mutations, 1 splice mutation, 1 frameshift mutation and 4 in-frame deletion mutations, 11 of which have not been reported. These 11 novel mutations were mainly concentrated in two genes, TWIST1 and TCF12. The mutation types included: 3 loss-of-function, 4 frameshift deletions, 3 missense mutations, and 1 frameshift insertion, of which 7 were de novo mutation.Conclusions:TWIST1 and TCF12 are common pathogenic genes in Chinese patients with non-syndromic craniosynostosis.

Objective:To explore the feasibility and safety of the prophylactic optic canal decompression in frontol-orbital fibrous dysplasia surgery by three-dimensional simulation design and computer assisted navigation.Methods:A retrospected study was conducted in Huashan Hospital affiliated to Fudan University.Patients with stable fronto-orbital fibrous dysplasia were recruited from January 2016 to June 2020. Preoperatively, three-dimensional simulation design was used to design the scope of resection. Then a subtotal resection of fibrous dysplasia lesion was performed by computer assisted navigation and reshaping of the orbit rim was achieved by preserving the fronto-orbital bandeau. Meanwhile, the intracanal and intraorbital parts of optic nerve canal decompression was performed. Follow-up of the pre-op and post-op difference of the frontal bulge point, the lateral forehead point and orbitofrontal point of the affected side, the degree of proptosis, visual acuity and fundus were analyzed by paired t test. Results:A total of 7 patients were recruited, including 2 males and 5 females, with an average age of 22.5 years. The average follow-up time was 11.4 months, and the difference in exophthalmos between the two sides improved from an average of (6.7±1.6) mm before operation to an average of(2.9±1.1) mm at 6 months after operation, which was statistically significant ( P<0.001). The difference between the pre-op and post-op of the frontal bulge point on the affected side also improved from (18.1±3.4) mm before surgery to (3.1±3.5)mm( P=0.001) immediately after surgery and (4.0±3.6) mm( P=0.001)at 6 months after surgery. The difference of lateral forehead point improved from(21.4±4.1) mm before surgery to (1.8±1.9) mm( P<0.001) immediately after surgery and (2.5±2.1) mm( P<0.001) at 6 months after surgery, and the difference of orbitofrontal point improved from(12.2±2.5) mm before surgery to (2.3±3.0) m( P=0.004) immediately after surgery and (2.7±2.9) mm( P=0.006) at 6 months after surgery. The average uncorrected visual acuity of the affected side before operation was 4.5, and it was 4.6 6 months after operation, with no statistical difference( P>0.05). Conclusions:Using 3D simulation to design the scope of resection and computer assisted navigation to decompress the optic canal in patients with stable fronto-orbital fibrous dysplasia, which can safely and effectively protect the optic nerve and accurately improve the frontal-orbital shape.

Objective:To explore the feasibility and safety of the prophylactic optic canal decompression in frontol-orbital fibrous dysplasia surgery by three-dimensional simulation design and computer assisted navigation.Methods:A retrospected study was conducted in Huashan Hospital affiliated to Fudan University.Patients with stable fronto-orbital fibrous dysplasia were recruited from January 2016 to June 2020. Preoperatively, three-dimensional simulation design was used to design the scope of resection. Then a subtotal resection of fibrous dysplasia lesion was performed by computer assisted navigation and reshaping of the orbit rim was achieved by preserving the fronto-orbital bandeau. Meanwhile, the intracanal and intraorbital parts of optic nerve canal decompression was performed. Follow-up of the pre-op and post-op difference of the frontal bulge point, the lateral forehead point and orbitofrontal point of the affected side, the degree of proptosis, visual acuity and fundus were analyzed by paired t test. Results:A total of 7 patients were recruited, including 2 males and 5 females, with an average age of 22.5 years. The average follow-up time was 11.4 months, and the difference in exophthalmos between the two sides improved from an average of (6.7±1.6) mm before operation to an average of(2.9±1.1) mm at 6 months after operation, which was statistically significant ( P<0.001). The difference between the pre-op and post-op of the frontal bulge point on the affected side also improved from (18.1±3.4) mm before surgery to (3.1±3.5)mm( P=0.001) immediately after surgery and (4.0±3.6) mm( P=0.001)at 6 months after surgery. The difference of lateral forehead point improved from(21.4±4.1) mm before surgery to (1.8±1.9) mm( P<0.001) immediately after surgery and (2.5±2.1) mm( P<0.001) at 6 months after surgery, and the difference of orbitofrontal point improved from(12.2±2.5) mm before surgery to (2.3±3.0) m( P=0.004) immediately after surgery and (2.7±2.9) mm( P=0.006) at 6 months after surgery. The average uncorrected visual acuity of the affected side before operation was 4.5, and it was 4.6 6 months after operation, with no statistical difference( P>0.05). Conclusions:Using 3D simulation to design the scope of resection and computer assisted navigation to decompress the optic canal in patients with stable fronto-orbital fibrous dysplasia, which can safely and effectively protect the optic nerve and accurately improve the frontal-orbital shape.

Objective:To explore the common pathogenic gene mutation in non-syndromic craniosynostosis in Chinese population.Methods:Patients with non-syndromic craniosynostosis were recruited in Huashan Hospital Affiliated to Fudan University from March 2018 to December 2020. A clinical questionnaire was designed to collect the general information of the patients. The gene panel was designed by entering the keywords craniosynostosis and gene panel in PubMed, extracting all relevant literature from January 1995 to May 2017. The gene library was sequenced on the Illumina HiSeq X platform, and bioinformatic analysis and pathogenic analysis were performed.Results:A total of 237 literatures were reviewed in the PubMed and Ovid databases, and the total sample was 3 375 patients, of which 1 822 cases (54%) were detected with corresponding mutations, involving 21 pathogenic genes. Based on the mutation detection rate of not less than 0.4%, 12 genes were selected in the gene panel: FGFR2, TWIST1, FGFR3, EFNB1, FGFR1, SKI, POR, RAB23, TCF12, MSX2, SMAD3 and ERF. A total of 109 patients with non-syndromic craniosynostosis were recruited in this study, including 62 males and 47 females; the average age was 2.1 years old. All participants denied family history. The average age at childbearing of father was 28.3 years old and of mother was 26.7 years old. Fourteen different pathogenic/probable pathogenic mutation loci were found in the gene sequences of 19 patients. The mutation rate was 17.4%(19/109). The 14 mutation varients were distributed in 5 genes (FGFR2, TWIST1, TCF12, EFNB1, and FGFR3). The 14 mutations can be classified into 5 missense mutations, 3 nonsense mutations, 1 splice mutation, 1 frameshift mutation and 4 in-frame deletion mutations, 11 of which have not been reported. These 11 novel mutations were mainly concentrated in two genes, TWIST1 and TCF12. The mutation types included: 3 loss-of-function, 4 frameshift deletions, 3 missense mutations, and 1 frameshift insertion, of which 7 were de novo mutation.Conclusions:TWIST1 and TCF12 are common pathogenic genes in Chinese patients with non-syndromic craniosynostosis.