OBJECTIVE: To explore the clinical phenotypes and genetic diagnosis of 2 sporadic cases for cleidocranial dysplasia. METHODS: The clinical data of two cases of CCD admitted to the Third Affiliated Hospital of Zhengzhou University on December 16, 2021 and December 9, 2021 were analyzed retrospectively, and the whole exome sequencing (WES), chromosome microarray analysis and copy number variation sequencing were performed. RESULTS: The main ultrasonographic findings of the fetus had included poorly calcified skull bones, budging of parieto-occipital area, compression and deformation of skull, and loss of nasal bone. The infant's clinical phenotypes included delayed closure of anterior fontanelle, recurrent respiratory tract infection, growth retardation, and clavicular hypoplasia. By WES analysis, the fetus was found to harbor a heterozygous c.911_914delinsTTT variant of the RUNX2 gene, whilst the infant was found to harbor a heterozygous c.1008delT variant of the RUNX2 gene. Both variants were verified by Sanger sequencing to have occurred de novo. CONCLUSION For sporadic cases featuring cleidocranial dysplasia, prenatal ultrasonography is particularly important. Hypoplastic clavicle, skull calcification and nasal bone absence are the main features. Diagnosis should also be suspected for infants featuring growth retardation, recurrent respiratory tract infections and clavicular dysplasia. The identification of the c.911_914delinsTTT and c.1008delT variants of the RUNX2 gene has facilitated genetic counseling and prenatal diagnosis, and also expanded the mutational spectrum of the RUNX2 gene.
Female ; Humans ; Pregnancy ; Cleidocranial Dysplasia/genetics* ; Core Binding Factor Alpha 1 Subunit ; DNA Copy Number Variations ; Growth Disorders ; Retrospective Studies

OBJECTIVE: To detect the genetic variant of a child with cleidocranial dysplasia (CCD) and to find out the causation of the illness. METHODS: Gene variant was identified by the second generation targeted sequencing and Sanger sequencing. RESULTS: The gene sequencing revealed that the RUNX2 gene had c.196C>T(p.Glu66*) nonsense variant, which was predicted to be a pathogenic variant according to the ACMG guidelines(PVS1+PS2). CONCLUSION The variant of c.196C > T in the RUNX2 gene may be the cause of the child with CCD, and the novel variant enriches the RUNX2 gene variant spectrum.
Asians/genetics* ; Child ; China ; Cleidocranial Dysplasia/genetics* ; Core Binding Factor Alpha 1 Subunit/genetics* ; Humans ; Mutation

OBJECTIVE: To analyze the clinical features and pathogenic variant in a Chinese pedigree affected with cleidocranial dysplasia (CCD). METHODS: Clinical data of 8 patients from the pedigree was collected, including physical examination and X-ray images of head, face, spine, limbs, and mouth. Peripheral blood samples were collected from 6 affected members for the extraction of genomic DNA. The proband and other 3 patients were subjected to trio-whole exome sequencing. Candidate variant was verified by Sanger sequencing of the other 2 affected members from the pedigree. RESULTS: This pedigree has included 22 members (8 affected) from four generations. Genetic testing revealed that the proband has harbored a novel pathogenic variant of the RUNX2 gene [NM_001024630: c.1268_1277del (p.P425Afs*56)], which was inherited from her mother and carried by all affected members in the pedigree. The same variant was not detected among the unaffected members, suggesting co-segregation with the phenotype. CONCLUSION The c.1268_1277del (p.P425Afs*56) variant of the RUNX2 gene probably underlay the pathogenesis of CCD in this pedigree. Genetic testing has facilitated the definite diagnosis and enabled prenatal diagnosis.
Humans ; Pregnancy ; Female ; Cleidocranial Dysplasia/genetics* ; Pedigree ; Core Binding Factor Alpha 1 Subunit/genetics* ; Phenotype ; China ; Mutation

Objective: To summarize the clinical characteristics of patients with cleidocranial dysplasia (CCD) and analyze their treatment methods. Methods: From January 2000 to December 2020, patients with CCD who completed comprehensive treatment in the Department of Orthodontics and the First Dental Clinic, School and Hospital of Stomatology, China Medical University were retrospectively analyzed. A total of 14 CCD patients [7 males and 7 females, aged (16.1±4.5) years] were collected. There were 153 impacted permanent teeth in this study. In addition to the teeth that needed to be extracted due to special conditions, 147 impacted teeth were pulled into the dentition using closed traction. Patients were divided into adolescent group (≥12 years and<18 years, 10 patients) and adult group (≥18 years, 4 patients). Failure rate of traction was compared between the two groups. Factors affecting the success rate of closed traction such as vertical position of teeth (high, middle and low) and horizontal position of the teeth (palatal, median and buccal) were analyzed. Results: The incidence of maxillary impacted teeth [69.3% (97/140)] was higher than that of mandibular impacted teeth [40% (56/140)]. The difference was statistically significant (χ²=24.22, P<0.001). The supernumerary teeth were mainly located in the premolar area 61.4% (21/44), and most of them were in the palatal region of the permanent teeth 95.5% (42/44). They were generally located at the same height or the occlusal side of the corresponding permanent teeth. The success rate of closed traction was 93.9% (138/147). The success rate in the adolescent group [98.2% (108/110)] was higher than that in the adult group [81.1% (30/37)], and the difference was significant (χ²=14.09, P<0.05). Failure after closed traction of 9 teeth was found totally, including 7 second premolars. The success rate of traction in impacted second premolars at different vertical (χ²=11.44, P<0.05) and horizontal (χ²=9.71, P<0.05) positions in alveolar bone was different significantlly. The success rates of the second premolars were high (15/16), middle (12/13), low (2/7), and lingual palatine (10/17), median (19/19), lip-buccal (0/0), respectively. Conclusions: The closed traction of impacted teeth in patients with CCD was effective, and the age was the main variable affecting the outcome. The success rate of traction in impacted second premolars located in low position vertically or in palatal position was low, which required close observation during treatment.
Adolescent ; Adult ; Bicuspid ; Child ; Cleidocranial Dysplasia/therapy* ; Female ; Humans ; Male ; Mandible ; Retrospective Studies ; Tooth, Supernumerary/surgery* ; Young Adult

OBJECTIVE: To explore the genetic basis for a Chinese patient featuring cleidocranial dysplasia(CCD). METHODS: Genomic DNA was extracted from peripheral blood samples of the patient and his parents. Whole exome sequencing (WES) was carried out for the patient, and suspected variant was verified by Sanger sequencing. RESULTS: WES has identified a missense c.460G>T (p.Val154Phe) (GRCh37/hg19) variant of the RUNX2 gene. The variant was located in the Runt domain, a highly conserved region (PM1); it was not present in either the Genome Aggregation Database or the 1000 Genomes Project (PM2), and was predicted to have a deleterious effect on the gene product by multiple in silico prediction tools (PP3); the clinical phenotype of the patient was highly consistent with that of cleidocranial dysplasia (PP4). Furthermore, the variant was unreported in medical literature and was absent in both parents (PS2). Based on the American College of Medical Genetics and Genomics guidelines, the c.460 G>T variant of RUNX2 gene was predicted to be pathogenic (PS2+PM1+PM2+PP3+PP4). CONCLUSION The c.460G>T (p.Val154Phe) variant of the RUNX2 gene probably underlay the clinical phenotype in the patient. Above finding has enabled accurate diagnosis and expanded the spectrum of RUNX2 variants.
China ; Cleidocranial Dysplasia/genetics* ; Core Binding Factor Alpha 1 Subunit/genetics* ; Humans ; Mutation ; Whole Exome Sequencing

Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal dysplasia whose most common features include late closure of fontanelles, absent or hypoplastic clavicles, and dental abnormalities. This disorder is primarily due to mutations in RUNX2 (CBFA1) gene. Here we present a Filipino child with clinical and radiologic features of CCD who was also diagnosed with B-cell acute lymphoblastic leukemia (ALL). On history, the patient’s father and paternal grandfather also presented with short stature and similar facial features. Association of leukemia and CCD has been noted in the literature. Hence, this report adds to the potential role of RUNX2 gene in leukemogenesis. With the potential predisposition to developing leukemia, this provides implications in genetic counselling and possible recommendations for surveillance later on.
Cleidocranial Dysplasia ; Leukemia

Cleidocranial dysplasia is a rare autosomal dominant hereditary disease characterized by abnormal skeletal and dental development. In this work, a case of cleidocranial dysplasia is reported, and a new frameshift mutation is confirmed by gene detection.
Cleidocranial Dysplasia ; Core Binding Factor Alpha 1 Subunit ; Diagnostic Tests, Routine ; Humans ; Mutation

Identification of certain abnormalities of the chest wall can be extremely helpful in correctly diagnosing a number of syndromic conditions and systemic diseases. Additionally, chest wall abnormalities may sometimes constitute diagnoses by themselves. In the present pictorial essay, we review a number of such conditions and provide illustrative cases that were retrospectively identified from our clinical imaging database. These include pentalogy of Cantrell, Klippel-Feil syndrome, cleidocranial dysplasia, Poland syndrome, osteopetrosis, neurofibromatosis type 1, Marfan syndrome, Gardner syndrome, systemic sclerosis, relapsing polychondritis, polymyositis/dermatomyositis, ankylosing spondylitis, hyperparathyroidism, rickets, sickle cell anemia, thalassemia, tuberculosis, septic arthritis of the sternoclavicular joint, elastofibroma dorsi, and sternal dehiscence.
Anemia, Sickle Cell ; Arthritis, Infectious ; Cleidocranial Dysplasia ; Diagnosis ; Gardner Syndrome ; Hyperparathyroidism ; Klippel-Feil Syndrome ; Marfan Syndrome ; Neurofibromatosis 1 ; Osteopetrosis ; Pentalogy of Cantrell ; Poland Syndrome ; Polychondritis, Relapsing ; Retrospective Studies ; Rickets ; Scleroderma, Systemic ; Spondylitis, Ankylosing ; Sternoclavicular Joint ; Thalassemia ; Thoracic Wall ; Tuberculosis

This report describes 3 cases of cleidocranial dysplasia (CCD) and presents relevant findings on long-term follow-up radiographic images of impacted permanent teeth with delayed eruption. Radiographic images of 3 CCD patients were reviewed retrospectively. These images were mainly composed of panoramic and skull radiographs, and the follow-up periods were 3, 13, and 13 years, respectively. The distinct features revealed by the images were described, and the eruption state of impacted permanent teeth was evaluated. The features common to the 3 cases were multiple supernumerary teeth, the presence of Wormian bone, underdevelopment of the maxilla and the maxillary sinus, and clavicular hypoplasia. The eruption of impacted permanent teeth was not observed without proper dental treatment in adult CCD cases, even after long time periods had elapsed. When proper orthodontic force was applied, tooth movement was observed in a manner not significantly different from the general population.
Adult ; Cleidocranial Dysplasia ; Follow-Up Studies ; Humans ; Jaw ; Maxilla ; Maxillary Sinus ; Radiography ; Retrospective Studies ; Skull ; Tooth Movement ; Tooth ; Tooth, Supernumerary

Cleidocranial dysplasia (CCD) is an autosomal-dominant disease characterized by the delayed closure of cranial sutures, defects in clavicle formation, supernumerary teeth, and delayed tooth eruption. Defects in the Runt-related transcription factor 2 (RUNX2), a master regulator of bone formation, have been identified in CCD patients. The aim of this study was to identify the molecular genetic causes in a CCD family with delayed tooth eruption.The 23-year-old female proband and her mother underwent clinical and radiographic examinations, and all coding exons of the RUNX2 were sequenced. Mutational analysis revealed a single nucleotide deletion mutation (NM_001024630.4 : c.357delC) in exon 3 in the proband and her mother. The single C deletion would result in a frameshift in translation and introduce a premature stop codon [p.(Asn120Thrfs*24)]. This would result in the impaired function of RUNX2 protein, which may be the cause of delayed eruption of permanent teeth in the family.
Clavicle ; Cleidocranial Dysplasia ; Clinical Coding ; Codon, Nonsense ; Core Binding Factor Alpha 1 Subunit ; Cranial Sutures ; Exons ; Female ; Humans ; Molecular Biology ; Mothers ; Osteogenesis ; Sequence Deletion ; Tooth ; Tooth Eruption ; Tooth, Supernumerary ; Transcription Factors ; Young Adult