Craniofacial Abnormalities ; genetics ; Humans ; Mutation ; Tooth Abnormalities ; genetics

The first three disorders discussed are abnormalities of bone: too little bone in cleidocranial dysplasia caused by mutations in RUNX2; too much bone in fibrodysplasia ossificans progressiva with overexpression of BMP4; and abnormal bone in McCune-Albright syndrome and fibrous dysplasia caused by mutations in GNAS1. Disorders of the sonic hedgehog signaling network are discussed next, including holoprosencephaly and the nevoid basal cell carcinoma syndrome, the former being caused by sonic hedgehog (SHH) mutations and the latter being caused by patched mutations (PTCH).
Basal Cell Nevus Syndrome ; genetics ; Craniofacial Abnormalities ; genetics ; Gene Expression Regulation, Developmental ; Holoprosencephaly ; genetics ; Humans ; Mutation

OBJECTIVETo explore the genetic basis for a patient with oculodentodigital dysplasia.

METHODSGenomic DNA was extracted from peripheral blood samples from the patient and his parents. Whole-exome sequencing was carried out for the trio family. Suspected mutation was verified by Sanger sequencing.

RESULTSA de novo c.412G>A mutation of the GJA1 gene was identified in the patient, which was validated by Sanger sequencing.

CONCLUSIONThe c.412G>A mutation of the GJA1 gene probably underlies the disease in the patient.

Adult ; Connexin 43 ; genetics ; Craniofacial Abnormalities ; genetics ; Exome ; Eye Abnormalities ; genetics ; Foot Deformities, Congenital ; genetics ; Humans ; Male ; Mutation ; Sequence Analysis, DNA ; Syndactyly ; genetics ; Tooth Abnormalities ; genetics

Objective: To discuss the clinical and genetic features of intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures (IDDBCS). Methods: The clinical and genetic records of a patient who was diagnosed with IDDBCS caused by PHF21A gene variation at Children's Hospital Capital Institute of Pediatrics in 2021 were collected retrospectively. Using " PHF21A gene" as the keyword, relevant articles were searched at CNKI, Wanfang Data and PubMed from establishment of databases to February 2023. Clinical and genetic features of IDDBCS were summarized in the combination of this case. Results: An 8 months of age boy showed overgrowth (height, weight and head circumference were all higher than the 97^th percentile of children of the same age and sex) and language and motor developmental delay after birth, and gradually showed autism-like symptoms like stereotyped behavior and poor eye contact. At 8 months of age, he began to show epileptic seizures, which were in the form of a series of spastic seizures with no reaction to adrenocorticotropic hormone but a good response to vigabatrin. Physical examination showed special craniofacial appearances including a prominent high forehead, sparse eyebrows, broad nasal bridge, and downturned mouth with a tent-shaped upper lip. The patient also manifested hypotonia. Whole exome sequencing showed a de novo heterogeneous variant, PHF21A (NM_001101802.1): c.54+1G>A, and IDDBCS was diagnosed. A total of 6 articles (all English articles) were collected, involving this case and other 14 patients of IDDBCS caused by PHF21A gene variation. Clinical manifestations were intellectual disability or developmental delay (15 patients), craniofacial anomalies (15 patients), behavioral abnormalities (12 patients), seizures (9 patients), and overgrowth (8 patients). The main pathogenic variations were frameshift variations (8 patients). Conclusions: IDDBCS should be considered when patients show nervous developmental abnormalities, craniofacial anomalies, seizures and overgrowth. PHF21A gene variation detection helps to make a definite diagnosis.
Male ; Humans ; Child ; Intellectual Disability/genetics* ; Developmental Disabilities/genetics* ; Retrospective Studies ; Seizures/genetics* ; Craniofacial Abnormalities/genetics* ; Histone Deacetylases/genetics*

BACKGROUND: Citation analysis is a recognized scientometric method of classifying cited articles according to the frequency of which they have been referenced. The total number of citations an article receives is considered to reflect it's significance among it's peers. METHODS: Until now, a bibliometric analysis has never been performed in the specialty of craniofacial anomalies and craniofacial surgery. This citation analysis generates an extensive list of the 50 most influential papers in this developing field. Journals specializing in craniofacial surgery, maxillofacial surgery, plastic surgery, neurosurgery, genetics and pediatrics were searched to demonstrate which articles have cultivated the specialty within the past 55 years. RESULTS: The results show an intriguing compilation of papers which outline the fundamental knowledge of craniofacial anomalies and the developments of surgical techniques to manage these patients. CONCLUSIONS: This citation analysis provides a summation of the current most popular trends in craniofacial literature. These esteemed papers aid to direct our decision making today within this specialty.
Bibliometrics ; Craniofacial Abnormalities ; Decision Making ; Genetics ; Humans ; Neurosurgery ; Pediatrics ; Surgery, Oral ; Surgery, Plastic

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a child with Intellectual developmental disorder with behavioral abnormalities and craniofacial malformations without epilepsy (IDDBCS). METHODS: A child who had visited the Lianyungang Maternal and Child Health Care Hospital in April 2021 was selected as the study subject. Clinical data of the child were collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents and subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing of his family members. RESULTS: The child, a 3-year-and-4-month-old male, had presented with global developmental delay and cranial malformation. Genetic testing revealed that he has harbored a heterozygous c.1703delA (p.K568Sfs9) variant of the PHF21A gene, for which both of his parents were of the wild type. This low-frequency variant may alter the structure and function of the protein product. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was classified as a pathogenic variant (PVS1+PS2+PM2_Supporting). CONCLUSION The heterozygous c.1703delA (p.K568Sfs9) variant of the PHF21A gene probably underlay the IDDBCS in this patient.
Child ; Male ; Humans ; Infant ; Developmental Disabilities/genetics* ; Craniofacial Abnormalities/genetics* ; Seizures/genetics* ; Intellectual Disability/genetics* ; Problem Behavior ; Mutation

OBJECTIVETo identify pathogenic mutation in a pedigree affected with craniofacial and skeletal abnormalities featuring an autosomal dominant inheritance.

METHODSClinical data and peripheral venous blood samples of the pedigree were collected. A total of 326 exons of skeletal disease-related genes were screened using Roche NimbleGen probes, and the results were confirmed by Sanger sequencing. Suspected variants were analyzed by bioinformatic software.

RESULTSA novel heterozygous mutation c.480C>A (p.160K>N) of HDAC4, the pathogenic gene for brachydactyly mental retardation syndrome, was found in the affected proband, his father and uncle. The proband and his father also carried a novel heterozygous c.880-882delAAG (p.294delK) mutation of TRPS1, the pathogenic gene for tricho-rhino-phalangeal syndrome. Bioinformatic analysis suggested that both mutations are pathogenic. In addition, three novel genetic variants, namely c.4817G>A (p.1606S>L) of MLL2, c.83A>G (p.28H>R) of TP63, and c.1712G>C (p.571T>S) of ERCC2, were also identified in this family.

CONCLUSIONThe HDAC4 c.480C>A (p.160K>N) mutation probably underlies the disease in this pedigree, while the TRPS1 c.880-882delAAG (p.294delK) mutation may be related with certain features of the affected family members. Genetic analysis has facilitated the diagnosis of this complex disease.

Asian Continental Ancestry Group ; genetics ; Craniofacial Abnormalities ; genetics ; Female ; Genetic Testing ; methods ; Heterozygote ; Humans ; Infant ; Male ; Mutation ; genetics ; Pedigree

BACKGROUNDSotos syndrome is an overgrowth syndrome with characteristic facial gestalt and mental retardation of variable severity. Haploinsufficiency of the NSD1 gene has been implicated as the major cause of Sotos syndrome, with a predominance of microdeletions reported in Japanese patients. This study was conducted to investigate into the spectrum of NSD1 gene mutations in southern Chinese patients with Sotos syndrome.

METHODSThirty-six Chinese patients with Sotos syndrome and two patients with Weaver syndrome were subject to molecular testing.

RESULTSNSD1 gene mutations were detected in 26 (72%) Sotos patients. Microdeletion was found in only 3 patients, while the other 23 had point mutations (6 frameshift, 8 nonsense, 2 spice site, and 7 missense). Of these, 19 mutations were never reported. NSD1 gene mutations were not found in the two patients with Weaver syndrome.

CONCLUSIONSMost cases of Sotos syndrome are caused by NSD1 gene defects, but the spectrum of mutations is different from that of Japanese patients. Genotype-phenotype correlation showed that patients with microdeletions might be more prone to congenital heart disease but less likely to have somatic overgrowth. The two patients with Weaver syndrome were not found to have NSD1 gene mutations, but the number was too small for any conclusion to be drawn.

Abnormalities, Multiple ; genetics ; Brain ; abnormalities ; Child, Preschool ; Craniofacial Abnormalities ; genetics ; Developmental Disabilities ; genetics ; Gene Deletion ; Growth Disorders ; genetics ; Humans ; Infant ; Intracellular Signaling Peptides and Proteins ; genetics ; Mutation ; Nuclear Proteins ; genetics ; Syndrome

OBJECTIVE: To analyze the clinical and molecular genetic characteristics of patient with Kleefstra syndrome 1. METHODS: Clinical data, chromosomal karyotype and whole genome copy number variations (CNVs) of the patient were analyzed. RESULTS: The patient was found to have a karyotype of 45,XX,-9[4]/46,XX,r(9)(p24q34)[56]. Whole-genome CNVs detection revealed that she has carried a heterozygous deletion of approximately 670 kb at 9q34.3, which encompassed the entire EHMT1 gene. The region is strongly associated with Kleefstra syndrome (1/9q telomere deletion). In addition, the patient also had heterozygous deletion of 9pter, which may predispose to formation of ring chromosome 9. CONCLUSION The child was diagnosed with Kleefstra syndrome type 1 in conjunct with ring chromosome 9.
Child ; Chromosome Deletion ; Chromosomes, Human, Pair 9 ; genetics ; Craniofacial Abnormalities ; genetics ; DNA Copy Number Variations ; Female ; Heart Defects, Congenital ; genetics ; Humans ; Intellectual Disability ; genetics ; Ring Chromosomes

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