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 explore the genotype-phenotype relationship in a child with Opitz G/BBB syndrome (OS) with mild clinical phenotype. METHODS: A child with motor developmental delay as the initial symptom admitted to Xi'an Children's Hospital on June 10, 2021 was selected for this study. Clinical data were collected, and peripheral blood samples were obtained from the child and his mother. Whole exome sequencing (WES) was performed to identify genetic variant in the child. Candidate variant were verified by Sanger sequencing to assess inheritance patterns and pathogenicity. Real-time fluorescence quantitative PCR (RT-qPCR) and Western blot (WB) analyses were conducted to evaluate the effects of the variant on mRNA and protein expression, respectively, using recombinant expression plasmids generated in vitro. This study was approved by the Medical Ethics Committee of Xi'an Children's Hospital (Ethics No. 20240045). RESULTS: The child, a 9-month-and-7-day-old boy, presented with a low nasal bridge, hypertelorism, and difficulty sitting independently. Echocardiography revealed an atrial septal defect. WES identified a homozygous variant in the MIDI gene, c.1483C>T (p.R495X), which was confirmed by Sanger sequencing and found to be inherited from the mother.Recombinant expression plasmids were successfully constructed. RT-qPCR analysis showed that the variant significantly reduced MIDI gene mRNA expression, while WB results indicated that the variant led to the production of a truncated protein. CONCLUSION The mild clinical phenotype of OS in this child may be attributed to the mRNA degradation escape mechanism induced by the nonsense variant c.1483C>T (p.R495X) in the MIDI gene. These findings provide valuable diagnostic insights for this pedigree and contribute to the understanding of the genotype-phenotype correlation in OS.
Humans ; Male ; Infant ; Transcription Factors/metabolism* ; Microtubule Proteins/genetics* ; Craniosynostoses/genetics* ; Hypospadias/genetics* ; Codon, Nonsense/genetics* ; RNA, Messenger/metabolism* ; Female ; RNA Stability/genetics* ; Phenotype ; Nuclear Proteins/genetics* ; Ubiquitin-Protein Ligases ; Esophagus/abnormalities* ; Hypertelorism

OBJECTIVE: To preliminarily verify the effectiveness of self-designed artificial condyle-mandibular distraction (AC-MD) complex in the treatment of Pruzansky type ⅡB and Ⅲ hemifacial microsomia (HFM) through model test. METHODS: Five children with Pruzansky type ⅡB and Ⅲ HFM who were treated with mandibular distraction osteogenesis (MDO) between December 2016 and December 2021 were selected as the subjects. There were 3 boys and 2 girls wih an average age of 8.4 years (range, 6-10 years). Virtual surgery and model test of AC-MD complex were performed according to preoperative skull CT of children. The model was obtained by three-dimensional (3D) printing according to the children's CT data at a ratio of 1∶1. The occlusal guide plate was designed and 3D printed according to the children's toothpaste model. The results of the model test and the virtual surgery were matched in three dimensions to calculate the error of the residual condyle on the affected side, and the model test was matched with the actual skull CT after MDO to measure and compare the inclination rotation of the mandible, the distance between the condylar of the healthy side and the residual condyle of the affected side, and the lengthening length of the mandible. RESULTS: The error of residual condyle was (1.07±0.78) mm. The inclination rotation of the mandible, the distance between the condylar of the healthy side and the residual condyle of the affected side, and the lengthening length of the mandible after 3D printing model test were significantly larger than those after MDO ( P<0.05). CONCLUSION In the model test, the implantation of AC-MD complex can immediately rotate the mandible to the horizontal position and improve facial symmetry, and the residual condyle segment can be guided close to the articular fossa or the preset pseudoarticular position of the skull base after operation.
Male ; Child ; Female ; Humans ; Goldenhar Syndrome/surgery* ; Mandible/surgery* ; Osteogenesis, Distraction/methods* ; Printing, Three-Dimensional ; Facial Asymmetry/surgery*

Humans ; Goldenhar Syndrome ; Phenotype ; Mutation ; DNA-Binding Proteins/genetics* ; Protein Tyrosine Phosphatases/genetics* ; Peptide Elongation Factors/genetics* ; Ribonucleoprotein, U5 Small Nuclear/genetics*

Objective:By analyzing the clinical phenotypic characteristics and gene sequences of two patients with Treacher Collins syndrome（TCS）, the biological causes of the disease were determined. Then discuss the therapeutic effect of hearing intervention after bone bridge implantation. Methods:All clinical data of the two family members were collected, and the patients signed the informed consent. The peripheral blood of the proband and family members was extracted, DNA was extracted for whole exome sequencing, and Sanger sequencing was performed on the family members for the mutation site.TCOF1genetic mutations analysis was performed on the paitents. Then, the hearing threshold and speech recognition rate of family 2 proband were evaluated and compared under the sound field between bare ear and wearing bone bridge. Results:In the two pedigrees, the probands of both families presented with auricle deformity, zygomatic and mandibular hypoplasia, micrognathia, hypotropia of the eye fissure, and hypoplasia of the medial eyelashes. The proband of Family 1 also presents with specific features including right-sided narrow anterior nasal aperture and dental hypoplasia, which were consistent with the clinical diagnosis of Treacher Collins syndrome. Genetic testing was conducted on both families, and two heterozygous mutations were identified in the TCOF1 gene: c. 1350_1351dupGG（p. A451Gfs*43） and c. 4362_4366del（p. K1457Efs*12）, resulting in frameshift mutations in the amino acid sequence. Sanger sequencing validation of the TCOF1 gene in the parents of the proband in Family 1 did not detect any mutations. Proband 1 TCOF1 c. 1350_1351dupGG heterozygous variants have not been reported previously. The postoperative monosyllabic speech recognition rate of family 2 proband was 76%, the Categories of Auditory Performance（CAP） score was 6, and the Speech Intelligibility Rating（SIR） score was 4. Assessment using the Meaningful Auditory Integration Scale（MAIS） showed notable improvement in the patient's auditory perception, comprehension, and usage of hearing aids. Evaluation using the Glasgow Children's Benefit Inventory and quality of life assessment revealed significant improvements in the child's self care abilities, daily living and learning, social interactions, and psychological well being, as perceived by the parents. Conclusion:This study has elucidated the biological cause of Treacher Collins syndrome, enriched the spectrum of TCOF1 gene mutations in the Chinese population, and demonstrated that bone bridge implantation can improve the auditory and speech recognition rates in TCS patients.
Child ; Humans ; Mandibulofacial Dysostosis/genetics* ; Quality of Life ; Speech ; Parents ; Mutation ; Nuclear Proteins/genetics* ; Phosphoproteins/genetics*

The human homologue of mouse progressive ankylosis protein(ANKH)is an inorganic pyrophosphate transport regulator,which regulates tissue mineralization by controlling the level of inorganic pyrophosphate.It plays an important role in the pathogenesis and development of bone and joint diseases,such as ankylosing spondylitis,craniometaphyseal dysplasia,and articular cartilage calcification.This review summarizes the progress of research on ANKH and the above-mentioned diseases.
Ankylosis ; Humans ; Hyperostosis ; Hypertelorism ; Joint Diseases ; Mice ; Mutation

OBJECTIVE: To delineate the clinical and genetic features of a fetus with micrognathia, low-set ears, microtia, polyhydramnios and anechoic stomach by ultrasonography. METHODS: Whole exome sequencing (WES) was carried out to detect genetic variant in the fetus, for which routine chromosomal karyotyping and chromosomal microarray analysis (CMA) yielded no positive finding. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. RESULTS: WES revealed that the fetus has carried a de novo nonsense c.2302C>T (p.Q768X) variant in exon 23 of the EFTUD2 gene, which was detected in neither parent. The variant was unreported previously and may lead to premature termination of the translation of EFTUD2 protein at the 768th amino acid. Bioinformatic analysis predicted the amino acid to be highly conserved and may alter the structure and function of the EFTUD2 protein. CONCLUSION The c.2302C>T variant of the EFTUD2 gene probably underlay the mandibulofacial dysostosis Guion-Almeida type in the fetus. Discovery of the novel variant has enriched variant spectrum of the EFTUD2 gene and provided a basis for genetic counseling and prenatal diagnosis for the family.
Female ; Fetus ; Humans ; Mandibulofacial Dysostosis/genetics* ; Mutation ; Peptide Elongation Factors/genetics* ; Phenotype ; Pregnancy ; Ribonucleoprotein, U5 Small Nuclear/genetics*

Tetrasomy 9p syndrome is a rare chromosomal abnormality syndrome whose most common features include hypertelorism, malformed ears, bulbous nose and microretrognathia. These features present as a result of an additional two copies of the short arm of chromosome 9. Here we present a neonate with characteristic facial features of hypertelorism, downslanted palpebral fissure, bulbous nose, small cupped ears, cleft lip and palate, and downturned corners of the mouth. Clinical features were consistent with the cytogenetic analysis of tetrasomy 9p. In general, clinicians are not as familiar with the features of tetrasomy 9p syndrome as that of more common chromosomal abnormalities like trisomies 13, 18, and 21. Hence, this case re-emphasizes the importance of doing the standard karyotyping for patients presenting with multiple congenital anomalies. Also, this is the first reported case of Tetrasomy 9p syndrome in Filipinos.
Isochromosomes ; Hypertelorism

Treacher Collins syndrome is a congenital craniofacial malformation with autosomal dominant inheritance as the main genetic pattern. In this condition, the biosynthesis of ribosomes in neural crest cells and neuroepithelial cells is blocked and the number of neural crest cells that migrate to the craniofacial region decreases, causing first and second branchial arch dysplasia. Definite causative genes include treacle ribosome biogenesis factor 1 (tcof1), RNA polymerase Ⅰ and Ⅲ subunit C (polr1c), and RNA polymerase Ⅰ and Ⅲ subunit D (polr1d). This paper provides a review of research of three major patho-genic genes, pathogenesis, phenotypic research, prevention, and treatment of the syndrome.
DNA-Directed RNA Polymerases ; genetics ; Humans ; Mandibulofacial Dysostosis ; genetics ; Neural Crest ; Nuclear Proteins ; Phosphoproteins

Frontonasal dysplasia is an uncommon congenital anomaly with diverse clinical phenotypes and highly variable clinical characteristics, including hypertelorism, a broad nasal root, median facial cleft, a missing or underdeveloped nasal tip, and a widow's peak hairline. Frontonasal dysplasia is mostly inherited and caused by the ALX genes (ALX1, ALX3, and ALX4). We report a rare case of a frontonasal dysplasia patient with mild hypertelorism, a broad nasal root, an underdeveloped nasal tip, an accessory nasal tag, and a widow's peak. We used soft tissue re-draping to achieve aesthetic improvements.
Humans ; Hypertelorism ; Phenotype