Clinical Study On Surgical Reconstruction And Identification Of The Pathogenic Genes Of Congenital Syndactyly

Part Ⅰ:Dorsal cross-shaped advancement flap for the treatment of congenital syndactylySection 1-The design of the cross-shaped advancement flapPurpose:We conducted this study to measure the relative anatomic data of the webspace of the hand,and designed a cross-shaped advancement flap for webspace reconstruction in treatment of congenital syndactyly.Methods:The diameter of the index,ring and little fingers at the level of distal point of web(L1),the distance between the midpoints of the adjacent MCP joint(L2),and the distance from the distal point of the web to the level of the MCP joint(L3)were measured.The data were analyzed by SPSS 19.0 software,and the correlation and regression analysis were conducted to abtain the relation of these results.We regarded the webspace and basal lateral walls of the adjacent fingers as a "V" composing of three equal squares.In these squares,side length is equal to the diameter of the smaller adjacent finger.Based on these considerations,we devised a "cross-shaped" advancement flap on the dorsal side of the metacarpophalangeal(MCP)joint to reconstruct the commissure and flexion crease in syndactyly.The flap was composed of five squares,of which the diagonal length served as the distance between the midpoints of the adjacent MCP joints.Results:The measurement was performed and the data were achieved in 43 children,including 25 males and 18 females.The children aged from 1 year 8 months to 14 years,with an average of 9.2 years.After regression analysis,distance between the midpoints of the adjacent MCP joints(L2)was approximately equal to 1.414 times of the diameter of the finger body(L1),while the L3 was about 1.5 times of L2.Side length of the squares of the cross-shaped flap were approximately equal to the diameter of the finger when the distance between midpoints of the adjacent MCP joints served as the diagonal length.Conclusions:We considered webspace and basal lateral walls of the adjacent fingers as a "V" composing of three equal squares.Base on this consideration,the cross-shaped flap composed of five squares,of which the distance between midpoints of the adjacent MCP joints served as the diagonal length is available to reconstruct the webspace.Section 2-Dorsal cross-shaped advancement flap for the Reconstruction of webspace in congenital syndactylyPurpose:The use of sizable dorsal flaps for webspace reconstruction without skin grafting can minimize the complications in syndactyly correction.We described the technique details and reported the results of a cross-shaped advancement flap for reconstruction of the webspace and coverage of the lateral sides of the bases of the separated fingers in congenital syndactyly.Methods:From June 2018 to July 2020,15 patients with simple or complex syndactyly for webspace reconstruction with a dorsal cross-shaped advancement flap were retrospectively studied.The patients aged from 5 to 144 months,with an average age of24.2 months.Out of these 15 patients,bilateral sides were involved in 6 patients.Withey grading for web-creep evaluation was conducted for postoperative evaluation.Vancouver Scar Scale(VSS)was used to assess scar hyperlasia,and Visual Analogue Scale(VAS)was applied to evaluate the subjective satisfaction of the children’s families with the reconstructed finger appearance,pain and function.Results:There was no perioperative complication in this group.During an 8 to 17 months follow-up period,all the reconstructed webspaces provided satisfactory appearance,and there was no obvious web creep.The scars on the dorsum of the patients’ hand were acceptable.No secondary correction was needed in this group.The average score of Withey scale was 0.1,and VSS was 1.5.The VAS score of appearance,VAS score of pain and VAS score of function were 1.8,0.2 and 1.1,respectively.Conclusions:This technique can reconstruct the webspace and cover the lateral wall of the fingers for syndactyly correction.Section 3-Contiguous cross-shaped advancement flap for the Reconstruction of webspace in brachysyndactyly(Poland Syndrome)in A single stagePurpose:To report the technique and results of vascular grafting,the contiguous crossshaped advancement flap for reconstruction of the webspace in syndactyly release for the patients with brachysyndactyly(Poland syndrome).Also,we reported the the anatomy of the palmar digital arteries in the patients with Poland syndrome,and Color doppler was used to evaluate the patients.Methods:From January 2013 to June 2018,sixty patients with Poland syndrome were included in this retrospective study.The level of the common arterial bifurcation of the conjoint fingers was identified by using Color Doppler.Digital artery anatomy was divided into different types with thproximal 1/3 of the proximal phalanx as the reference point,The distances between the bifurcation points and the reference points were measured and recorded.Normal type(≤0 mm),slightly elevation type(0～5 mm);Moderate elevation type(5-10 mm),severe elevation type(>10 mm),absent type(with only one artery between the adjancent fingers).Based on the vascular anatomy types,the different surgical plans were designed.The contiguous cross-shaped advancement flaps were used to reconstruct the webspace in syndactyly release of Poland syndrome.Postoperative follow-up was conducted to assess the accuracy of localization of digital vascular crisis,and morphology of the webspace was accessed by modified Withey score and Swanson hand function score.Results:The coincidence rate of preoperative color doppler vascular localization in 62 patients with 186 pairs of syndactylosis was 98%,and the normal type was 61.8%(115/186).Slight elevation type accounted for 24.2%(45/186),moderate elevation type accounted for 8.1%(15/186),severe elevation type accounted for 4.8%(9/186),absent type accounted for 1.1%(2/186).Multiple syndactyly releases and web reconstruction in one stage were performed in seventeen cases.Of them vascular grafting was used in 5 cases.The operations were successfully completed,all the flap and skin grafting were completely alive,and there were no early complications such as infection and skin necrosis.All the patients were followed for 8-35 months postoperatively,with an average of 18.7 months.All patients had a reconstruction depth of digital webbed at nearly 1/3 of the proximal phalanx.Both the appearance and function were satisfactory.The depth,width and slope of the new webs were normal without conspicuous scar.Withey score was 0～1,with an average score of 0.19.Conclusion:The contiguous cross-shaped advancement flap for reconstruction of the multiple webspaces in syndactyly release of Poland syndrome can obtain favorable results.In addition,preoperative vascular assessment is essential to sydactyly correction for Poland syndrome.Blood vessel classification based on color doppler benefits to guide the surgical plan.Part Ⅱ:Genetic research on two families with syndactylyPurpose:Syndactyly are commonly seen in the congenital limb deformities,and most of them are in an autosomal dominant fashion.The variants in GLI3 gene are closely related to the congenital limb malformations.However,the causes underlying syndactyly are not well understood.Methods:we conducted a whole-exome sequencing and linkage analysis on two fourgeneration Chinese families with polydactyly and syndactyly.Then c.2374C>T and c.1728C>A mutant plasmids were transfected to HEK293T cells and mice limb bud cells to explore the functional consequences of these variants.Western blot and real-time quantitative PCR were applied to studied the expression of GLI3 and SHH in the functional study of the pathogenic genes.Results:In these two families,the known GLI3 variant(c.2374C>T)and the novel GLI3 variant(c.1728C>A)contributed to polydactyly and syndactyly.Additionally,the GLI3 c.2374C>T mutant plasmid led to truncated GLI3 protein and the GLI3 c.1728C>A mutant plasmid led to degraded GLI3 protein.Simultaneously,we demonstrated that the GLI3 mutant plasmids led to decreased Shh expression in mice limb bud cells.Conclusion:We demonstrated that the novel GLI3 variant(c.1728C>A)and known GLI3 variant(c.2374C>T)contributed to the malformations in two four-generation pedigrees with polydactyly and syndactyly by affecting SHH signaling.