Patient 1, a 3-year-6-month-old male, presented with feeding difficulties and delayed motor development. He exhibited poor responsiveness at birth, weak crying, intellectual and motor delays, low immunity, recurrent respiratory infections, hypotonia of the limbs, and distinctive facial features (low-set ears, double chin, and high arched palate), as well as a single transverse palmar crease on the right hand. Genetic testing revealed a c.1096C>T heterozygous variant in the SMARCB1 gene. Patient 2, a 3-year-old male, presented with developmental delay and distinctive facial features. Genetic testing identified the same pathogenic mutation as in Patient 1. The two patients are unrelated, and clinical phenotyping and genetic testing confirmed both cases as Coffin-Siris syndrome type 3. Coffin-Siris syndrome is a rare genetic disorder, and early genetic testing can aid in diagnosis.
Child, Preschool ; Humans ; Male ; Abnormalities, Multiple/genetics* ; Chromosomal Proteins, Non-Histone/genetics* ; Ear/abnormalities* ; Face/abnormalities* ; Hand Deformities, Congenital/genetics* ; Intellectual Disability/genetics* ; Micrognathism/genetics* ; Mutation ; Neck/abnormalities*

Objective:This aims to investigate the diagnostic and evaluative value of MRI for lymphatic malformations in the head, neck, and facial regions of children. Methods:A retrospective analysis was conducted on the MRI imaging data of 31 cases of head, neck, and facial lymphatic malformations in children admitted to the Department of Otolaryngology, Head and Neck Surgery, Children's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, from January 2022 to January 2024. Results:The MRI images of this group of cases primarily displayed irregular morphology（80.6%, 25/31）, thin-walled cysts（80.6%, 25/31）, and compression of surrounding tissues. The boundaries were clear（100%, 31/31）, with characteristics of invasive and drill-like growth（93.5%）. The cyst walls or internal septa exhibited high signal intensity on T1WI, low signal intensity on T2WI, and mild to moderate enhancement（100%）. The contents of the cysts showed low signal intensity on T1WI, high signal intensity on T2WI, and no enhancement（35.5%, 11/31）. Mixed signals with varying degrees of enhancement were observed in 20 cases（64.5%）. There were 29 cases of multilocular cysts（93.5%, 29/31）, and 11 cases of fluid-fluid levels（35.5%）. The MRI diagnostic accuracy for this group of cases was 100%. Conclusion:Lymphatic Malformations of head, neck and facial region in children have very characteristic features on MRI, such as typical thin wall, clear boundaries, irregular shapes, invasive growth, no enhancement, multilocular cystic masses, fluid-fluid level, etc. Furthermore, it is more appropriate for children with lymphatic malformations owing to its non-radiation and non-invasive benefits. Diagnosing lymphatic malformations in the head, neck, and facial region in children should begin with this.
Humans ; Retrospective Studies ; Lymphatic Abnormalities/diagnostic imaging* ; Magnetic Resonance Imaging ; Neck/diagnostic imaging* ; Head/diagnostic imaging* ; Face/diagnostic imaging* ; Child ; Male ; Female ; Child, Preschool ; Adolescent ; Infant

OBJECTIVE: To explore the genetic basis for two Chinese pedigrees affected with Coffin-Siris syndrome (CSS). METHODS: Whole exome sequencing (WES) was carried out for the probands. Candidate variants were verified by Sanger sequencing of the probands and their family members. RESULTS: The two probands were respectively found to harbor a heterozygous c.5467delG (p.Gly1823fs) variant and a heterozygous c.5584delA (p.Lys1862fs) variant of the ARID1B gene, which were both of de novo in origin and unreported previously. Based on the guidelines of American College of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+PS2+PM2). CONCLUSION The c.5467delG (p.Gly1823fs) and c.5545delA (p.Lys1849fs) variants of the ARID1B genes probably underlay the CSS in the two probands. Above results have enabled genetic counselling and prenatal diagnosis for the pedigrees.
Abnormalities, Multiple ; China ; DNA-Binding Proteins/genetics* ; Face/abnormalities* ; Hand Deformities, Congenital ; Humans ; Intellectual Disability ; Micrognathism ; Neck/abnormalities* ; Pedigree ; Transcription Factors/genetics*

OBJECTIVE: To explore the genetic basis for two unrelated patients with global developmental delay and coarse facial features. METHODS: Clinical data and family history of the two pedigrees were collected. Whole exome sequencing and Sanger sequencing were carried out to detect potential variants. RESULTS: The two patients have presented with global developmental delay, coarse facies, muscular hypotonia, congenital heart disease, and pectus excavatum, and were found to harbor two de novo loss-of-function variants of the ARID1B gene, namely c.3586delC (p.Gln1196Serfs*15) and c.4954_4957delACGT (p.Thr1652Glyfs*31). Both variants were unreported previously. CONCLUSION The nonsense variants of the ARID1B gene probably underlay the etiology in these patients. Above finding has enriched the genotypic and phenotypic spectrum of the disease and provided a basis for prenatal diagnosis.
Abnormalities, Multiple ; China ; DNA-Binding Proteins/genetics* ; Face/abnormalities* ; Facies ; Hand Deformities, Congenital/genetics* ; Humans ; Intellectual Disability/genetics* ; Micrognathism/genetics* ; Neck/abnormalities* ; Transcription Factors/genetics*

OBJECTIVE: To explore the genetic basis of a child with recurrent infection, multiple malformation and dysmorphism. METHODS: The child and his parents were subjected to trio whole exome sequencing. RESULTS: The child had a complaint of fever and cough, with long and thin eye fissures and long eyelashes. Genetic testing revealed that the child has carried a non-triplet deletion of the KDM6A gene, which was unreported previously. The variant resulted in frameshift and premature termination of the translation. His parents were both of the wild type for the locus. After antibiotic and immunoglobulin treatment, the severe secondary pneumonia caused by immunodeficiency has improved. CONCLUSION With combined laboratory test, imaging examination and genetic testing, the child was ultimately diagnosed with Kabuki syndrome type 2. The characteristics of immunodeficiency of Kabuki syndrome may render conventional antibiotic treatment ineffective, which deserves clinical attention.
Abnormalities, Multiple ; Child ; DNA-Binding Proteins/genetics* ; Face/abnormalities* ; Genetic Testing ; Hematologic Diseases ; Histone Demethylases/genetics* ; Humans ; Neoplasm Proteins/genetics* ; Nuclear Proteins/genetics* ; Phenotype ; Pneumonia ; Vestibular Diseases

OBJECTIVE: Clinical examination and molecular genetic analysis were carried out for one case with special facial features with developmental retardation, hearing impairment and cleft lip and palate. METHODS: The intelligence test, hearing test, and MRI test were performed. At the same time, the blood were collected to detect the copy number variation of the whole genome with the chromosomal karyotype analysis and the chromosomal microarray analysis (CMA). And the whole exome sequencing (WES) was used to analyze the pathogenic variant. RESULTS: The children had mild mental retardation and the IQ was 61. There was moderate hearing loss in both ears(left ear 60 dB, right ear 65 dB). And bilateral horizontal hypoplasia of semicircular canal was found by cranial MRI test. No copy number abnormality was found by chromosome karyotype analysis and chromosome microarray analysis in peripheral blood. And whole exome sequencing suggested that there was heterozygous pathogenic variants in KMT2D gene (p.Leu545Argfs*385). CONCLUSION The patient has a peculiar face and multiple system defects, and was diagnosed as Niikawa-Kuroki syndrome type I by KMT2D gene variant. The whole exome sequencing is helpful for the diagnosis of complex genetic diseases.
Abnormalities, Multiple ; Child ; Cleft Lip ; Cleft Palate ; DNA Copy Number Variations ; Face/abnormalities* ; Hematologic Diseases ; Humans ; Vestibular Diseases

OBJECTIVE: To detect pathogenic variant of the FGD1 gene in a boy with Aarskog-Scott syndrome. METHODS: Genetic variant was detected by high-throughput sequencing. Suspected variant was verified by Sanger sequencing. The nature and impact of the candidate variant were predicted by bioinformatic analysis. RESULTS: The child was found to harbor a novel c.1906C>T hemizygous variant of the FGD1 gene, which has led to conversion of Arginine to Tryptophane at codon 636(p.Arg636Trp). The same variant was found in his mother but not father. Based on the American College of Medical Genetics and Genomics guidelines, the c.1906C>T variant of FGD1 gene was predicted to be likely pathogenic(PM1+PM2+PM5+PP2+PP3+PP4). CONCLUSION The novel c.1906C>T variant of the FGD1 gene may underlay the Aarskog-Scott syndrome in this child. Above finding has enabled diagnosis for the boy.
Child ; Dwarfism ; Face/abnormalities* ; Genetic Diseases, X-Linked ; Genitalia, Male/abnormalities* ; Guanine Nucleotide Exchange Factors/genetics* ; Hand Deformities, Congenital/genetics* ; Heart Defects, Congenital ; Humans ; Male ; Mutation

The maxillofacial skeleton is the basis of the contour of the face. Orthognathic surgery and facial contouring surgery change jaw tissue and affect facial appearance in different manners. Orthognathic surgery is the main method to correct dental and maxillofacial deformities. It changes the shape of the jaw and improves the occlusal relationship by changing the three-dimensional position of the jaw. Facial contouring surgery mainly adopts the method of "bone reduction", which changes the "amount"of the jawbone by cutting a part of the bone tissue to improve the facial appearance, generally without changing oral function. The combined use of orthognathic surgery and facial contouring surgery is becoming increasingly common in clinical practice. This also requires oral and maxillofacial surgeons to have a holistic consideration of the comprehensive correction of maxillofacial bone deformity, and to perform comprehensive analysis of jaw deformities and jaw plastic surgery to achieve the most ideal results. The author's team has been engaged in the clinical work of orthognathic surgery and facial contouring surgery and accumulated rich clinical experience in the comprehensive correction of maxillofacial bone deformity. In this article, the indications, treatment goals, treatment modes, treatment methods, and key points in the surgical operations of comprehensive maxillofacial bone surgery were summarized.
Face/surgery* ; Facial Bones ; Humans ; Maxillofacial Abnormalities ; Orthognathic Surgery ; Orthognathic Surgical Procedures

OBJECTIVE: To explore the genotype-phenotype correlation in a child with Kabuki syndrome type 1 (KS1) caused by a mosaic frameshift variant of KMT2D gene. METHODS: Trio-based whole exome sequencing (WES) was carried for the patient and her parents. Candidate variant was verified by Sanger sequencing. RESULTS: The proband, a 3-year-and-2-month-old Chinese girl, presented with distinctive facial features, cognitive impairment, mild developmental delay, dermatoglyphic abnormalities, minor skeletal anomalies, ventricular septal defect, and autistic behavior. Trio-based WES revealed that the proband has carried a de novo mosaic frameshit variant of the KMT2D gene, namely NM_003482.3:c.13058delG (p.Pro4353Argfs*31) (GRCh37/hg19), for which the mosaicism rate was close to 21%. The variant was unreported previously and was confirmed by Sanger sequencing. Chromosomal microarray analysis (CMA) has revealed no pathogenic or likely pathogenic copy number variations. Compared with previously reported cases, our patient has presented obvious behavior anomalies including autism, anxiety and sleep problems, which were rarely reported. CONCLUSION This study has expanded the spectrum of KMT2D gene variants, enriched the clinical phenotypes of KS1, and facilitated genetic counseling for the family.
Abnormalities, Multiple ; China ; DNA Copy Number Variations ; DNA-Binding Proteins/genetics* ; Face/abnormalities* ; Female ; Hematologic Diseases ; Humans ; Infant ; Neoplasm Proteins/genetics* ; Phenotype ; Vestibular Diseases

Schinzel-Giedion syndrome is a rare autosomal dominant genetic disease and has the clinical features of severe delayed development, unusual facies, and multiple congenital malformations. In this case report, a 14-month-old boy had the clinical manifestations of delayed development, unusual facies (prominent forehead, midface retraction, hypertelorism, low-set ears, upturned nose, and micrognathia), and multiple congenital malformations (including cerebral dysplasia, dislocation of the hip joint, and cryptorchidism). The karyotype analysis and copy number variations showed no abnormalities, and whole exon sequencing showed a de novo heterozygous missense mutation, c.2602G > A (p. D868N), in SETBP1 gene. Therefore, the boy was diagnosed with Schinzel-Giedion syndrome. Myoclonic seizures in this boy were well controlled by sodium valproate treatment, and his language development was also improved after rehabilitation treatment. Clinical physicians should improve their ability to recognize such rare diseases, and Schinzel-Giedion syndrome should be considered for children with unusual facies, delayed development, and multiple malformations. Gene detection may help with the diagnosis of this disease.
Abnormalities, Multiple ; diagnosis ; genetics ; Craniofacial Abnormalities ; diagnosis ; genetics ; Developmental Disabilities ; diagnosis ; Face ; abnormalities ; Hand Deformities, Congenital ; diagnosis ; genetics ; Humans ; Infant ; Intellectual Disability ; diagnosis ; genetics ; Male ; Nails, Malformed ; diagnosis ; genetics