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

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

OBJECTIVES: This study aims to explore the association between single nucleotide polymorphisms (SNPs) loci near the haplotype region hg19 chr9:100560865-100660865 of the forkhead box E1 (FOXE1) gene and the occurrence of non-syndromic cleft lip with or without cleft palate (NSCL/P) in western Han Chinese population. METHODS: In the first stage, our study recruited 159 NSCL/P patients and performed targeted region sequencing to screen SNPs loci near the haplotype region of the FOXE1 gene associated with NSCL/P. In the second stage, we selected 21 common SNPs and re-enrolled 1 000 non-syndromic cleft lip only (NSCLO) patients, 1 000 non-syndromic cleft palate only (NSCPO) patients, and 1 000 normal controls to verify the association. PLINK software was used to perform Hardy-Weinberg equilibrium (HWE) test. Association analysis for common variants, gene burden analysis for rare mutations, and function prediction of SNPs with non-synonymous mutations were performed using Mutation Taster and other software programs. RESULTS: In the first stage, 126 variants, including 76 single nucleotide variants and 50 insertion-deletions were identified. All the included SNPs confirmed to HWE, and the results of gene burden analysis and prediction of functional harmfulness for rare variants were not statistically significant. Association analysis showed that rs13292899 of the FOXE1 gene was significantly associated with NSCL/P (P=1.85E-27) and was also correlated with NSCLO (P=6.41E-23) and non-syndromic cleft lip with cleft palate (NSCLP) (P=2.36E-15) subtypes. In the validation phase, rs79268293 (P=0.013, P=0.022), rs10983951 (P=0.009 2, P=0.007 6), rs117227387 (P=0.009 2, P=0.007 6), rs3758250 (P=0.009 2, P=0.007 6), and rs116899397 (P=0.009 2, P=0.007 6) were significantly associated with NSCLO and NSCPO; rs13292899 (P=0.008 5), rs74606599 (P=0.008 3), rs143226042 (P=0.008 3), and rs117236550 (P=0.01) were associated with the occurrence of NSCLO; and rs12343182 (P=0.008 7), rs10119760 (P=0.012), rs10113907 (P=0.012), and rs13299924 (P=0.012) were associated with the occurrence of NSCPO. CONCLUSIONS This study found a new susceptible SNP rs13292899 of the FOXE1 gene that is closely associated with NSCL/P and NSCLO subtype and 13 other SNPs associated with NSCLO or NSCPO.
Female ; Humans ; Male ; China ; Cleft Lip/genetics* ; Cleft Palate/genetics* ; Forkhead Transcription Factors/genetics* ; Haplotypes ; Polymorphism, Single Nucleotide ; East Asian People/genetics*

OBJECTIVES: This study aims to investigate factors influencing dental arch development in patients aged 0-6 years with cleft palate after Sommerlad-Furlow (SF) palatoplasty. METHODS: A total of 183 patients who underwent primary SF repair for cleft lip and palate before 18 months of age were included. Follow-ups were conducted at different ages, and digital dental casts of the maxillary dental arch were obtained using 3-matic Research 12.0 software. The length and width of the dental arch and palate were measured to explore developmental changes in the maxillary dental arch of the patients after the procedure. The study also investigated the influence of gender, age, cleft palate type, and relaxation incision on maxillary dental arch development. RESULTS: After SF, maxillary dental arch measurements showed statistically significant differences between children aged 0-2 years and those aged 3-6 years (P<0.05). However, no statistically significant differences were observed among different age groups within the 3-6 years range. Statistically significant differences were detected between males and females, with males having greater width of the posterior dental arch and palate (P=0.001) and shorter length of the anterior dental arch and entire dental arch (P<0.05). The unilateral cleft lip and palate group had shorter dental arch length (P<0.01) and wider posterior palate (P<0.01) than the cleft palate only group. Maxillary dental arch measurements had no statistically significant differences between groups with or without a relaxing incision. CONCLUSIONS Gender and age influence the width of the maxillary dental arch in children aged 0-6 years after SF, while age and cleft palate type affect dental arch length.
Humans ; Child, Preschool ; Male ; Cleft Palate/surgery* ; Female ; Child ; Infant ; Dental Arch/growth & development* ; Maxilla/growth & development* ; Cleft Lip/surgery* ; Age Factors ; Sex Factors ; Palate/surgery* ; Infant, Newborn

Muenke syndrome is an autosomal dominant genetic disorder that is typically characterized by unilateral or bilateral coronal synostosis, macrocephaly, midface hypoplasia, and developmental delays. This article reports a case of Muenke syndrome with a soft cleft palate. A heterozygous missense mutation c.749C>G (p.P250A) was identified in the FGFR3 gene through genetic testing. The patient exhibited typical features including coronal synostosis, bilateral hearing loss, right accessory auricle, and developmental delays and underwent surgery to repair the soft cleft palate. Cases of Muenke syndrome with cleft palate in the literature are relatively rare, and common associated symptoms include coronal suture craniosynostosis and hearing impairment. This article reports a differential diagnosis with other craniosynostosis syndromes and provides a reference for clinical diagnosis and treatment.
Humans ; Cleft Palate/surgery* ; Craniosynostoses/diagnosis* ; Mutation, Missense ; Palate, Soft/abnormalities* ; Receptor, Fibroblast Growth Factor, Type 3/genetics*

OBJECTIVES: A stable, reliable, and easily implementable clinical diagnostic method for marginal velopharyngeal insufficiency (MVPI) was established on the basis of the subjective hearing judgement of hypernasality and objective examination of velopharyngeal closure to address the lack of unified diagnostic criteria for MVPI. METHODS: Nasopharyngeal fiberscopy and speech assessment results were collected from postoperative patients with cleft palate. These results were used to analyze the differences in the distribution of nasal resonance in patients with different velopharyngeal closure ratios and the correlation between velopharyngeal closure ratios and nasal resonance status. Mild-to-moderate hypernasality with its corresponding elopharyngeal closure ratio was employed to establish the diagnostic criteria of MVPI. The reproducibility of the criteria and whether the patients with MVPI diagnosed by using the criteria exhibited significantly different speech characteristics compared with other patients were verified. RESULTS: A strong correlation was found between velopharyngeal closure ratios and nasal resonance (P<0.001). Mild-to-moderate hypernasality mainly corresponded to velopharyngeal closure ratios ranging from 90% to 99%, and the combination of the two characteristics as the diagnostic criteria for MVPI demonstrated good consistency (Kappa value=0.789, P<0.001). Moreover, under the diagnostic criteria, significant differences in nasal resonance (P<0.001), nasal emission (P=0.007), and misarticulation (P<0.001) were found between patients with velopharyngeal insufficiency and those with MVPI. CONCLUSIONS Combining the subjective hearing judgement of mild-to-moderate hypernasality with velopharyngeal closure ratios over 90% under nasopharyngeal fiberscopy provides a reliable and effective clinical method for diagnosing MVPI.
Humans ; Velopharyngeal Insufficiency/physiopathology* ; Reproducibility of Results ; Cleft Palate/surgery* ; Male ; Female ; Child

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*