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*

OBJECTIVE: To analyze the clinical and genetic characteristics of an infant with craniosynostosis. METHODS: An infant who was admitted to Wuhan Children's Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology in April 2021 due to widening of the lateral ventricles for over a month was selected as the study subject. Clinical data of the patient was collected. Peripheral blood samples were collected from the infant and her parents for chromosomal karyotyping and whole exome sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. Relevant literature was retrieved from the PubMed, Wanfang and CNKI databases (up to December 2021) by using key words including ERF gene, craniosynostosis, ERF mutation, craniosynostosis and ERF-related craniosynostosis. RESULTS: The infant, a 1-month-and-16-day-old female, was found to have sagittal synostosis by cranial X-ray radiography. Genetic testing revealed that she has harbored a heterozygous c.787C>T (p.Q263*) variant of the ERF gene, which was not found in either parent. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted as pathogenic (PVS1+PS2+PM2_Supporting). In total 63 relevant cases were retrieved from the database, and a total of 64 individuals were analyzed by genetic testing. Most of the cases were sporadic and males. Multiple cranial sutures (including at least two of the sagittal suture, coronal suture, lambdoid suture, and frontal suture) were involved in 45.45% of the cases, and those with sagittal suture closure only have accounted for 20.00%. The main clinical manifestations have included hypertelorism, exophthalmos, development delay, malar dysplasia, etc. Chiari type 1 malformation may present in some patients. Variants of the ERF gene have mainly included splicing and deletional variants, and there was a strong genetic heterogeneity among the infants and their pedigrees. CONCLUSION The c.787C>T (p.Q263*) variant of the ERF gene probably underlay the craniosynostosis of this infant. Above finding has enriched the phenotype ~ genotype spectrum of the ERF gene.
Female ; Humans ; Cranial Sutures/surgery* ; Craniosynostoses/genetics* ; Genetic Testing ; Mutation ; Repressor Proteins/genetics* ; Infant

OBJECTIVE: To explore the clinical and genetic characteristics of a Chinese pedigree affected with Multiple synostoses syndrome type 1 (SYNS1). METHODS: Clinical data of the proband and her family members were collected. Genomic DNA was extracted from peripheral blood samples. Whole-exome sequencing (WES) and whole-genome sequencing (WGS) were carried out for the proband and her parents. RESULTS: The pedigree has comprised of 14 members from three generations, of whom six had manifested hearing loss, with other symptoms including proximal symphalangism, hemicylindrical nose, amblyopia, strabismus, brachydactyly, incomplete syndactyly, which fulfilled the diagnostic criteria for SYNS1. WES had detected no pathogenic single nucleotide variants and insertion-deletion (InDel) in the coding region of the NOG gene, whilst copy number variation (CNV) analysis indicated that there was a heterozygous deletion involving the NOG gene. WGS revealed a heterozygous deletion (54171786_55143998) in 17q22 of the proband. The CNV was classified as pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). CONCLUSION The heterozygous deletion in 17p22 involving the NOG gene probably underlay the pathogenesis of SYNS1 in this pedigree. Above finding has enriched the mutational spectrum of NOG. CNV should be considered when conventional sequencing has failed to detect any pathogenic variants in such patients.
Female ; Humans ; DNA Copy Number Variations ; East Asian People ; Pedigree ; Synostosis ; Phenotype

OBJECTIVE: To summarize the application and recent development of orthognathic surgery in treating syndromic craniosynostosis. METHODS: The related literature at home and abroad in recent years was extensively reviewed, and the indications, routine procedures, and protocols of orthognathic surgery in the treatment of syndromic craniosynostosis were summarized and analyzed. RESULTS: Craniosynostosis is a common congenital craniofacial malformation. Syndromic craniosynostosis usually involves premature fusion of multiple cranial sutures and is associated with other deformities. Orthognathic surgery is the necessary and effective means to improve the midfacial hypoplasia and malocclusion. Le Fort I osteotomy combined with sagittal split ramus osteotomy are the common surgical options. Orthognathic surgery should combine with craniofacial surgery and neurosurgery, and a comprehensive long-term evaluation should be conducted to determine the best treatment plan. CONCLUSION Orthognathic surgery plays an important role in the comprehensive diagnosis and treatment of syndromic craniosynostosis. The development of digital technology will further promote the application and development of orthognathic surgery in the treatment of syndromic craniosynostosis.
Humans ; Orthognathic Surgery ; Craniosynostoses/surgery* ; Osteotomy ; Osteotomy, Sagittal Split Ramus

Objective: To summarize the preliminary efficacy, perioperative management and complications of Le Fort Ⅲ osteotomy and midface distraction in patients with syndromic craniosynostosis by retrospective analysis, and to provide clinical experience for reference. Methods: From October 2017 to January 2020, 20 patients with syndromic craniosynostosis underwent Le Fort Ⅲ osteotomy and distraction in The Department of Oral and Maxillofacial Surgery of Peking University International Hospital, including 11 males and 9 females, were involved. The median age was 7 years (1.5 to 15 years). Preoperative risk prevention plan was put forward by multidisciplinary evaluation, and preoperative intervention was carried out. The diagnostic data of SNA, airway volume, polysomnography (PSG), ophthalmology and occlusal relationship were obtained through specialized examination, and osteotomy and distraction surgical plan was formulated through virtual surgical planning. CT was taken 1 week and 3, 6, 12 months after operation, PSG and eye protrudence examination were conducted to evaluate the therapeutic effect, syndrome type, multiple disciplinary treatment (MDT) intervention, occurrence and outcome of complications were summarized. Results: There were 15 cases of Crouzon syndrome and 5 cases of Pfeiffer syndrome. Sleep apnea was the first complaint in 18 cases and exophthalmia in 2 cases. Preoperative interventional therapy included 4 cases of adenoid surgery, 2 cases of continuous positive airway pressure and 2 cases of maxillary expansion. The most common surgical complications were accidental fracture (14/20 cases, 70%), cerebrospinal fluid fistula (2 cases), internal carotid cavernous sinus fistula (1 case), postoperative hyponatraemia (5 cases), crying syndrome (2 cases), wound infection (2 cases), trichiasis of lower eyelid (4 cases), and nasal malformation (1 case). Three cases underwent unplanned secondary surgery. SNA, airway volume and mean percutaneous arterial oxygen saturation (SpO₂) six months after operation were significantly higher than those before operation (F=10.09, P=0.001; F=5.13, P<0.001; F=10.78, P=0.001), and the protrusion and apnea hypopnea index were significantly lower than those before surgery (F=6.73, P=0.010; F=18.47, P<0.001). There were no significant differences in SNA, airway volume, mean SpO₂, ophthalmology between 6 months after surgery and 1 year after surgery (P>0.05). Conclusions: Perioperative safety assessment and early intervention of MDT is an effective diagnosis and treatment model of Le Fort Ⅲ osteotomy and distraction for syndromic craniosynosis. The operative complications are mainly local, and systemic complications are controllable.
Cephalometry ; Child ; Craniosynostoses/surgery* ; Female ; Humans ; Male ; Osteogenesis, Distraction ; Osteotomy, Le Fort ; Retrospective Studies ; Syndrome

OBJECTIVE: To conduct clinical and genetic analysis of two male patients with atypical Rett syndrome. METHODS: Collection of clinical data in the two patients and these parents; whole exome sequencing (WES) was used to detect the potential variants, which were verified by Sanger sequencing. X chromosome inactivation (XCI) detection is performed in the Patient 1's mother to detect the allelic expression difference of the MECP2 gene. RESULTS: Patient 1, a 5-year and 10-month-old boy, had mental disorders and mild intellectual disability (ID) (IQ: 54), whose mother had ID. Patient 2 was a 9-month and 18-day-old male presented with recurrent infections, respiratory insufficiency, hypotonia and global developmental delay. WES indentified a hemizygous mutation, c.499C>T (p.R167W), in the MECP2 gene in patient 1, which was inherited from his mother. The inactivation of X chromosome is skewed, and the expression ratio of wild-type and mutant MECP2 is 100%:0. Patient 2 was found a de novo splicing mutation, c.62+2_62+3del in the MECP2 gene. They were both reported pathogenic variant related to Rett syndrome. c.499C>T (p.R167W) was defined as likely pathogenic (PS1+PM2+PP3) and c.62+2_62+3del was pathogenic (PVS1+PM2+PM6) based on American College of Medical Genetics and Genomics standards and guidelines. CONCLUSION Both the two patients were diagnosed with rare male Rett syndrome, which had atypical clinical manifestations and large difference. Above foundings have revealed novel phenotypes in Chinese male patients with Rett syndrome.
Craniosynostoses ; Female ; Genetic Testing ; Humans ; Intellectual Disability/genetics* ; Male ; Methyl-CpG-Binding Protein 2/genetics* ; Mutation ; Phenotype ; Rett Syndrome/genetics*

Craniofacial malformation caused by premature fusion of cranial suture of infants has a serious impact on their growth. The purpose of skull remodeling surgery for infants with craniosynostosis is to expand the skull and allow the brain to grow properly. There are no standardized treatments for skull remodeling surgery at the present, and the postoperative effect can be hardly assessed reasonably. Children with sagittal craniosynostosis were selected as the research objects. By analyzing the morphological characteristics of the patients, the point cloud registration of the skull distortion region with the ideal skull model was performed, and a plan of skull cutting and remodeling surgery was generated. A finite element model of the infant skull was used to predict the growth trend after remodeling surgery. Finally, an experimental study of surgery simulation was carried out with a child with a typical sagittal craniosynostosis. The evaluation results showed that the repositioning and stitching of bone plates effectively improved the morphology of the abnormal parts of the skull and had a normal growth trend. The child's preoperative cephalic index was 65.31%, and became 71.50% after 9 months' growth simulation. The simulation of the skull remodeling provides a reference for surgical plan design. The skull remodeling approach significantly improves postoperative effect, and it could be extended to the generation of cutting and remodeling plans and postoperative evaluations for treatment on other types of craniosynostosis.
Child ; Computer Simulation ; Cranial Sutures/surgery* ; Craniosynostoses/surgery* ; Humans ; Infant ; Skull/surgery*

No abstract available.
Craniosynostoses ; Muscles

Intermetatarsal coalition (IC) is very rare; although few cases have been reported in foreign orthopedic journals, these have not originated in our country. We report the case of a 20-year-old man who complained of pain in the left forefoot only during long distance running (3 km). On examination, his foot shape, skin appearance, and gait were normal, with no plantar keratosis; however, the radiograph revealed coalition between the fourth and fifth metatarsals. Surgical excision was performed. In the histopathologic study, fibrous coalition was confirmed. This paper reports an uncommon case involving surgical excision of IC in the military service, involving active sport activity.
Foot ; Gait ; Humans ; Keratosis ; Metatarsal Bones ; Military Personnel ; Orthopedics ; Running ; Skin ; Sports ; Synostosis ; Young Adult

Craniofacial abnormalities are common. It is important to examine the fetal face and skull Epub ahead of print during prenatal ultrasound examinations because abnormalities of these structures may indicate the presence of other, more subtle anomalies, syndromes, chromosomal abnormalities, or even rarer conditions, such as infections or metabolic disorders. The prenatal diagnosis of craniofacial abnormalities remains difficult, especially in the first trimester. A systematic approach to the fetal skull and face can increase the detection rate. When an abnormality is found, it is important to perform a detailed scan to determine its severity and search for additional abnormalities. The use of 3-/4-dimensional ultrasound may be useful in the assessment of cleft palate and craniosynostosis. Fetal magnetic resonance imaging can facilitate the evaluation of the palate, micrognathia, cranial sutures, brain, and other fetal structures. Invasive prenatal diagnostic techniques are indicated to exclude chromosomal abnormalities. Molecular analysis for some syndromes is feasible if the family history is suggestive.
Brain ; Chromosome Aberrations ; Cleft Palate ; Cranial Sutures ; Craniofacial Abnormalities* ; Craniosynostoses ; Female ; Fetus ; Humans ; Magnetic Resonance Imaging ; Micrognathism ; Palate ; Pregnancy ; Pregnancy Trimester, First ; Prenatal Diagnosis ; Skull ; Ultrasonography ; Ultrasonography, Prenatal*