OBJECTIVE: To investigate the genetic etiology of a fetus diagnosed with Mandibulofacial dysostosis with microcephaly (MFDM). METHODS: A fetus that underwent prenatal diagnosis at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, on May 19, 2025 was selected for analysis. Results of fetal ultrasound findings, chromosomal karyotyping, copy number variation sequencing (CNV-seq), and whole-exome sequencing (WES) were collected. Sanger sequencing was performed for familial validation of the pathogenic variant. The Human Protein Atlas (HPA), STRING, and Simple ClinVar databases were queried to characterize the biological features of the candidate gene. Three-dimensional structures of the wild-type and variant proteins were modeled and analyzed, and the evolutionary conservation of the affected amino acid was assessed using UGENE. Prenatal phenotypes associated with EFTUD2 variants were summarized through a review of the literature. This study was approved by the Ethics Committee of Beijing Obstetrics and Gynecology Hospital, Capital Medical University (Ethics No.: 2025-KY-029-01). RESULTS: At 23⁺² weeks of gestation, ultrasound examination revealed bilateral microtia with low-set ears, mild micrognathia with a reduced mandibular-facial angle, a single umbilical artery, a slightly narrow aortic diameter, and trivial mitral regurgitation. Amniotic fluid karyotyping and CNV-seq showed no abnormalities. WES identified a de novo, previously unreported EFTUD2 variant, c.698dupA (p.V235Gfs*27), in the fetus. This frameshift variant is predicted to alter the structural integrity of the EFTUD2 protein. Literature review indicated that micrognathia and microtia or low-set ears are the most common sonographic features in fetuses with EFTUD2 variants, while secondary findings may include abnormal stomach bubble, cleft palate, single umbilical artery, gastrointestinal atresia, polyhydramnios, and reduced aortic diameter. CONCLUSION The EFTUD2: c.698dupA (p.V235Gfs*27) variant is likely the genetic cause underlying MFDM in this fetus.
Humans ; Mandibulofacial Dysostosis/diagnostic imaging* ; Microcephaly/diagnostic imaging* ; Female ; Pregnancy ; Ribonucleoprotein, U5 Small Nuclear/chemistry* ; Peptide Elongation Factors/chemistry* ; Fetus ; DNA Copy Number Variations/genetics* ; Adult ; Ultrasonography, Prenatal

OBJECTIVE: To investigate the effectiveness of Salter osteotomy combined with subtrochanteric shortening and derotational osteotomy in treating Tönnis type Ⅲ and Ⅳ developmental dysplasia of the hip (DDH) in children and explore the urgical timing. METHODS: A retrospective collection was performed for 74 children with Tönnis type Ⅲ and Ⅳ DDH who were admitted between January 2018 and January 2020 and met the selection criteria, all of whom were treated with Salter osteotomy combined with subtrochanteric shortening and derotational osteotomy. Among them, there were 38 cases in the toddler group (age, 18-36 months) and 36 cases in the preschool group (age, 36-72 months). There was a significant difference in age between the two groups ( P<0.05), and there was no significant difference in gender, side, Tönnis typing, and preoperative acetabular index (AI) ( P>0.05). During follow-up, hip function was assessed according to the Mckay grade criteria; X-ray films were taken to observe the healing of osteotomy, measure the AI, evaluate the hip imaging morphology according to Severin classification, and assess the occurrence of osteonecrosis of the femoral head (ONFH) according to Kalamchi-MacEwen (K&M) classification criteria. RESULTS: All operations of both groups were successfully completed, and the incisions healed by first intention. All children were followed up 14-53 months, with an average of 27.9 months. There was no significant difference in the follow-up time between the two groups ( P>0.05). At last follow-up, the excellent and good rates according to the Mckay grading were 94.73% (36/38) in the toddler group and 83.33% (30/36) in the preschool group, and the difference between the two groups was significant ( P<0.05). The imaging reexamination showed that all osteotomies healed with no significant difference in the healing time between the two groups ( P>0.05). There was no significant difference in AI between the two groups at each time point after operation ( P>0.05), and the AI in the two groups showed a significant decreasing trend with time extension ( P<0.05). The result of Severin classification in the toddler group was better than that in the preschool group at last follow-up ( P<0.05). There was no significant difference in the incidence of ONFH between the two groups ( P>0.05). In the toddler group, 2 cases were K&M type Ⅰ; in the preschool group, 3 were type Ⅰ, and 1 type Ⅱ. There was no dislocation after operation. CONCLUSION Salter osteotomy combined with subtrochanteric shortening and derotational osteotomy is an effective way to treat Tönnis type Ⅲ and Ⅳ DDH in children, and surgical interventions for children aged 18-36 months can achieve better results.
Humans ; Osteotomy/methods* ; Developmental Dysplasia of the Hip/diagnostic imaging* ; Retrospective Studies ; Male ; Child, Preschool ; Female ; Infant ; Femur/surgery* ; Child ; Treatment Outcome ; Hip Dislocation, Congenital/surgery*

OBJECTIVE: To evaluate the effectiveness of correcting post-traumatic equinovarus deformity using Ilizarov external fixation technique combined with limited osteotomy. METHODS: A retrospective analysis was conducted on clinical data from 29 patients with post-traumatic equinovarus deformity treated between July 2018 and March 2023. The cohort included 18 males and 11 females, with ages ranging from 15 to 57 years (mean, 24.3 years). All patients exhibited ankylosed ankle joints with equinovarus deformity. During surgery, external fixators were installed according to Ilizarov pinning principles, and minimally invasive osteotomy was performed at the ankle joint. Concurrently, soft tissue release was achieved via minimally invasive Achilles tendon lengthening. Postoperatively, multiplanar deformity correction was accomplished through gradual adjustment of the external fixator. The fixator was removed after bony union at the osteotomy site, followed by bracing. The surgical duration, intraoperative blood loss, fixator wear time, and complications were recorded. Postoperative outcomes included assessment of deformity correction and bony union at the osteotomy site. Functional improvement and pain relief were evaluated using pre- and post-operative scores from the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score and visual analogue scale (VAS) score. RESULTS: All 29 patients were followed up 12-24 months (mean, 18 months). The mean surgical duration was 85.6 minutes, with a mean intraoperative blood loss of 110 mL. Full deformity correction was achieved within 26-80 days (mean, 40.7 days) through progressive fixator adjustments. At correction completion, all ankles restored to a neutral or 5°-10° dorsiflexed position with plantigrade foot function. Superficial pin tract infections occurred in 3 patients (10.3%), resolved with local wound care, enhanced nursing, and oral antibiotics. No deep or systemic infections was observed. One patient sustained a calcaneal half-pin fracture due to a fall during fixator wear, but no bone fragment displacement occurred. No vascular or neurological complication was reported. Complete bony union was achieved at all osteotomy sites without nonunion. At last follow-up, the AOFAS ankle-hindfoot score improved from preoperative 42.7±8.7 to postoperative 65.7±9.3, and the VAS score decreased from preoperative 4.5±1.3 to postoperative 2.5±1.1, with significant differences ( P<0.05). Functional outcomes were rated as excellent in 14 cases, good in 13 cases, fair in 1 case, and poor in 1 case, with an excellent and good rate of 93.1%. CONCLUSION The progressive correction strategy combining Ilizarov external fixation technique with limited foot osteotomy effectively corrects post-traumatic equinovarus deformity while preserving soft tissue integrity. This method is associated with minimal, largely controllable complications and achieves alignment stability and fusion outcomes comparable to traditional open surgery, making it an effective treatment for complex foot and ankle deformities.
Humans ; Male ; Female ; Osteotomy/methods* ; Adult ; Retrospective Studies ; Ilizarov Technique ; Middle Aged ; Adolescent ; External Fixators ; Young Adult ; Treatment Outcome ; Ankle Joint/surgery* ; Clubfoot/etiology* ; Minimally Invasive Surgical Procedures/methods*

OBJECTIVE: To summarize the methods of ankle hinge position design in the correction of clubfoot deformity by Ilizarov method, and to explore its application value in the prevention of ankle dislocation. METHODS: A retrospective study was conducted including 28 patients with rigid clubfoot deformity (34 feet) who met the selection criteria and admitted between September 2021 and December 2024. There were 19 males and 9 females with an average age of 31.8 years (range, 19-47 years). According to Dimeglio classification, there were 21 feet of degree Ⅲ and 13 feet of degree Ⅳ. The causes were traumatic sequelae in 9 cases, congenital foot deformity in 15 cases, spina bifida sequelae in 1 case, peripheral neuropathy in 1 case, and cerebral palsy sequelae in 2 cases. The malformation lasted from 6 to 46 years, with an average of 29.3 years. All patients were treated with Ilizarov circular external fixator, and the hinge position of ankle joint was planned according to the standard lateral X-ray film of foot and ankle and the principle of Ilizarov limb deformity correction center of rotation angulation (CORA) before operation. The 2008 International Clubfoot Study Group (ICFSG) scoring system was used to evaluate the efficacy. RESULTS: The deformity of rigid clubfoot was completely corrected in all patients, and the patients could walk with plantar weight-bearing, and the ankle weight-bearing walking significantly improved when compared with that before operation. There was no complication such as ankle dislocation, talus impact or extrusion, local skin necrosis, needle tract infection, or numbness of extremities during the correction process. All patients were followed up 5-39 months, with an average of 18.1 months. At last follow-up, according to the ICFSG scoring system, 23 feet were excellent, 10 feet were good, and 1 foot was fair, and the excellent and good rate was 97%. CONCLUSION Designing the position of the ankle hinge according to the principle of CORA can effectively avoid ankle dislocation, talus impingement, tibiotalar joint extrusion, and other ankle adverse events in the process of correcting clubfoot deformity, which has good application value in clinical practice.
Humans ; Male ; Female ; Clubfoot/diagnostic imaging* ; Ilizarov Technique/instrumentation* ; Adult ; Retrospective Studies ; External Fixators ; Ankle Joint/diagnostic imaging* ; Middle Aged ; Joint Dislocations/prevention & control* ; Treatment Outcome ; Young Adult

OBJECTIVE: To explore the biomechanical characteristics and clinical application effects of three-dimensional (3D) printed osteotomy guide plate combined with Ilizarov technique in the treatment of rigid clubfoot. METHODS: A retrospective analysis was performed on the clinical data of 11 patients with rigid clubfoot who met the inclusion criteria and were admitted between January 2019 and December 2024. There were 6 males and 5 females, aged 21-60 years with an average of 43.2 years. Among them, 5 cases were untreated congenital rigid clubfoot, 4 cases were recurrent rigid clubfoot after previous treatment, and 2 cases were rigid clubfoot due to disease sequelae. All 11 patients first received slow distraction using Ilizarov technique combined with circular external fixator until the force lines of the foot and ankle joint were basically normal. Then, 1 male patient aged 24 years was selected, and CT scanning was used to obtain imaging data of the ankle joint and foot. A 3D finite element model was established and validated using the plantar stress distribution nephogram of the patient. After validation, the biomechanical changes of the tibiotalar joint under the same load were simulated after triple arthrodesis and fixation. The optimal correction angle of the hindfoot was determined to fabricate 3D-printed osteotomy guide plates, and all 11 patients underwent triple arthrodesis using these guide plates. The functional recovery was evaluated by comparing the American Orthopaedic Foot and Ankle Society (AOFAS) score, International Clubfoot Study Group (ICFSG) score, and 36-Item Short Form Survey (SF-36) score before and after operation. RESULTS: Finite element analysis showed that the maximum peak von Mises stress of the tibiotalar joint was at hindfoot varus 3° and the minimum at valgus 6°; the maximum peak von Mises stress of the 3 naviculocuneiform joints under various conditions appeared at lateral naviculocuneiform joint before operation, and the minimum appeared at lateral naviculocuneiform joint at neutral position 0°; the maximum peak von Mises stress of the 5 tarsometatarsal joints under various conditions appeared at the 2nd tarsometatarsal joint at hindfoot neutral position 0°, and the minimum appeared at the 1st tarsometatarsal joint at valgus 6°. Clinical application results showed that the characteristics of clubfoot deformity observed during operation were consistent with the preoperative 3D reconstruction model. All 11 patients were followed up 8-24 months with an average of 13.1 months. One patient had postoperative incision exudation, which healed after dressing change; the remaining patients had good incision healing. All patients achieved good healing of the osteotomy segments, with a healing time of 3-6 months and an average of 4.1 months. At last follow-up, the AOFAS score, SF-36 score, and ICFSG score significantly improved when compared with those before operation ( P<0.05). CONCLUSION The 3D-printed osteotomy guide plate combined with Ilizarov technique has favorable biomechanical advantages in the treatment of rigid clubfoot, with significant clinical application effects. It can effectively improve the foot function of patients and achieve precise and personalized treatment.
Humans ; Clubfoot/diagnostic imaging* ; Printing, Three-Dimensional ; Male ; Osteotomy/instrumentation* ; Female ; Ilizarov Technique/instrumentation* ; Adult ; Retrospective Studies ; Biomechanical Phenomena ; Middle Aged ; Bone Plates ; Young Adult ; Finite Element Analysis ; Treatment Outcome ; Ankle Joint/physiopathology* ; Tomography, X-Ray Computed ; External Fixators

OBJECTIVE: To investigate the effectiveness of applying a standardized rehabilitation process in correction of adult clubfoot with the Ilizarov technique. METHODS: Thirty-eight adult patients who underwent orthopedic treatment with Ilizarov technique for clubfoot between August 2022 and December 2024 were retrospectively analyzed. The patients were divided into a study group and a control group with 19 cases in each group according to the different rehabilitation management processes and methods. The differences in baseline data such as gender, age, side, and preoperative Holden walking function grading between the two groups were not significant ( P>0.05). In both groups, most of the clubfoot deformities were surgically corrected first, and the residual deformities were corrected by dynamic slow retraction with Ilizarov ring-type external fixation frame. The study group adopted standardized rehabilitation process management mode, including preoperative lower limb muscle strength training, postoperative pain and swelling management, weight-bearing management, gait and lower limb stability training. The control group adopted the conventional postoperative rehabilitation management mode. The occurrence of complications was recorded, including pin tract infection, ankle stiffness and pain, and deformity recurrence. Holden walking function grading was used to evaluate the walking ability of the patients. Clinical efficacy was evaluated by the QIN Sihe Deformity Correction Disability Repair and Functional Reconstruction Postoperative Efficacy Evaluation Scale. Patient satisfaction was evaluated by Likert score. RESULTS: Patients in both groups successfully completed surgery and rehabilitation and were followed up. The follow-up time ranged from 8 to 29 months, with a mean of 18.5 months. Among them, the follow-up time was (18.8±5.5) months in the study group and (18.2±5.7) months in the control group, and the difference between groups was not significant ( t=0.316, P=0.754). The postoperative incidences of pin tract infection, ankle stiffness and pain, and deformity recurrence in the study group were 10.53%, 5.26%, and 5.26%, respectively, and in the control group were 21.05%, 36.84%, and 15.79%, respectively. And the difference between groups in the incidence of ankle stiffness and pain was significant ( P=0.042). At last follow-up, both groups showed an improvement in Holden walking function grading compared to preoperative levels ( P<0.05), and the grading of the study group was significantly higher than that of the control group ( P=0.006). According to the QIN Sihe Deformity Correction Disability Repair and Functional Reconstruction Postoperative Efficacy Evaluation Scale, the grade difference between groups was not significant ( P=0.089), and the excellent and good rates of clinical efficacy in study group and control group were 89.47% (17/19) and 73.68% (14/19), respectively. Patient satisfaction in study group was significantly better than that in control group ( P=0.036). CONCLUSION Standardized rehabilitation process can effectively promote the postoperative functional recovery of adult clubfoot treated with Ilizarov technique, reduce the risk of complications and improve effectiveness.
Humans ; Ilizarov Technique/rehabilitation* ; Clubfoot/rehabilitation* ; Male ; Female ; Retrospective Studies ; Adult ; Treatment Outcome ; Young Adult ; Weight-Bearing ; Adolescent

BACKGROUND: An increased prevalence of cleft lip and/or palate (CL/P), a major congenital anomaly, has been observed in the offspring of women with elevated body mass index (BMI) before pregnancy. Likewise, gestational comorbidities, such as hypertension and diabetes mellitus, also increase the risk of CL/P; however, the risk linked to the coexistence of these conditions in women with higher BMI on birth prevalence of CL/P remains unclear. This study focused on the combined effects of a high BMI before pregnancy and gestational comorbidities on the birth prevalence of CL/P. METHODS: Among 98,373 live births from the Japan Environment and Children's Study (JECS), a nationwide birth cohort, 255 mothers of infants with CL/P (74, 112, and 69 infants born with cleft lip, cleft lip and palate, and isolated cleft palate, respectively) were included in the analyses. The association of CL/P birth prevalence with pre-pregnancy BMI and gestational comorbidities (hypertension and diabetes) was examined using multivariate logistic regression analyses after multiple imputations, with adjustments for several maternal (age at delivery, smoking habits, and alcohol intake) and child-related (sex and prevalence of other congenital diseases) variables, obtained through medical record transcriptions and self-reports on JECS transcription forms. RESULTS: Higher prevalence rates of overweight, gestational hypertension, and gestational diabetes mellitus were found in mothers of infants with CL/P (16.1%, 6.3%, and 4.7%, respectively) than in the control group (10.4%, 3.1%, and 3.1%, respectively). The odds ratio [95% confidence interval] for childbirth with CL/P was increased in mothers with high BMI before pregnancy (1.58 [1.11-2.24]). Furthermore, gestational hypertension and diabetes coexisting with high BMI additionally increased the odds ratios for childbirth with CL/P (2.91 [1.28-6.61] and 2.12 [0.87-5.19], respectively). CONCLUSION High maternal BMI, particularly when accompanied by gestational hypertension, was significantly associated with an increased prevalence of childbirth with CL/P.
Humans ; Female ; Cleft Lip/etiology* ; Cleft Palate/etiology* ; Pregnancy ; Japan/epidemiology* ; Prevalence ; Body Mass Index ; Adult ; Male ; Infant, Newborn ; Comorbidity ; Diabetes, Gestational/epidemiology* ; Risk Factors ; Young Adult ; Birth Cohort

Periodontal disease is a risk factor for many systemic diseases such as Alzheimer's disease and adverse pregnancy outcomes. Cleft palate (CP), the most common congenital craniofacial defect, has a multifaceted etiology influenced by complex genetic and environmental risk factors such as maternal bacterial or virus infection. A prior case-control study revealed a surprisingly strong association between maternal periodontal disease and CP in offspring. However, the precise relationship remains unclear. In this study, the relationship between maternal oral pathogen and CP in offspring was studied by sonicated P. gingivalis injected intravenously and orally into pregnant mice. We investigated an obvious increasing CP (12.5%) in sonicated P. gingivalis group which had inhibited osteogenesis in mesenchyme and blocked efferocytosis in epithelium. Then glycolysis and H4K12 lactylation (H4K12la) were detected to elevate in both mouse embryonic palatal mesenchyme (MEPM) cells and macrophages under P. gingivalis exposure which further promoted the transcription of metallopeptidase domain17 (ADAM17), subsequently mediated the shedding of transforming growth factor-beta receptor 1 (TGFBR1) in MEPM cells and mer tyrosine kinase (MerTK) in macrophages and resulted in the suppression of efferocytosis and osteogenesis in palate, eventually caused abnormalities in palate fusion and ossification. The abnormal efferocytosis also led to a predominance of M1 macrophages, which indirectly inhibited palatal osteogenesis via extracellular vesicles. Furthermore, pharmacological ADAM17 inhibition could ameliorate the abnormality of P. gingivalis-induced abnormal palate development. Therefore, our study extends the knowledge of how maternal oral pathogen affects fetal palate development and provides a novel perspective to understand the pathogenesis of CP.
Animals ; Female ; Porphyromonas gingivalis ; Pregnancy ; Mice ; Cleft Palate/etiology* ; Glycolysis

Congenital musculoskeletal and limb deformities (CMLD) seriously affect the physical and mental health of patients, and pose great challenges to healthcare systems worldwide. We explored the specific situation and changes of incidence, prevalence, disability-adjusted life years rates, and mortality of CMLD in under-5 children from 1990 to 2021 in different groups, including different regions, periods, genders and socio-demographic indices (SDI), through corresponding analytical models. Overall, the global disease burden of CMLD in under-5 children has decreased from 1990 to 2021. The disease burden of CMLD in under-5 children varied significantly among different regions and countries, and there was a strong correlation between the corresponding burden of disease and the level of SDI. In addition, cross-country inequality analysis showed that while absolute inequalities in the disease burden of CMLD in under-5 children have improved, relative inequalities have worsened. It is essential to reduce the global health impact of CMLD by implementing targeted interventions to improve health care in underdeveloped areas.
Humans ; Global Burden of Disease/trends* ; Child, Preschool ; Global Health/statistics & numerical data* ; Infant ; Male ; Prevalence ; Limb Deformities, Congenital/mortality* ; Musculoskeletal Abnormalities/mortality* ; Female ; Disability-Adjusted Life Years ; Incidence ; Infant, Newborn ; Cost of Illness ; Socioeconomic Factors

Congenital orofacial cleft, the most common birth defect in the maxillofacial region, exhibits a wide range of prognosis depending on the severity of deformity and underlying etiology. Non-syndromic congenital orofacial clefts typically present with milder deformities and more favorable treatment outcomes, whereas syndromic congenital orofacial clefts often manifest with concomitant organ abnormalities, which pose greater challenges for treatment and result in poorer prognosis. This consensus provides an elaborate classification system for varying degrees of orofacial clefts along with corresponding diagnostic and therapeutic guidelines. Results serve as a crucial resource for families to navigate prenatal screening results or make informed decisions regarding treatment options while also contributing significantly to preventing serious birth defects within the development of population.
Humans ; Cleft Lip/diagnosis* ; Cleft Palate/diagnosis* ; Consensus ; Prenatal Diagnosis ; Female