Objective: To analyze the clinical and genetic characteristics of pediatric patients with dual genetic diagnoses (DGD). Methods: Clinical and genetic data of pediatric patients with DGD from January 2021 to February 2022 in Peking University First Hospital were collected and analyzed retrospectively. Results: Among the 9 children, 6 were boys and 3 were girls. The age of last visit or follow-up was 5.0 (2.7,6.8) years. The main clinical manifestations included motor retardation, mental retardation, multiple malformations, and skeletal deformity. Cases 1-4 were all all boys, showed myopathic gait, poor running and jumping, and significantly increased level of serum creatine kinase. Disease-causing variations in Duchenne muscular dystrophy (DMD) gene were confirmed by genetic testing. The 4 children were diagnosed with DMD or Becker muscular dystrophy combined with a second genetic disease, including hypertrophic osteoarthropathy, spinal muscular atrophy, fragile X syndrome, and cerebral cavernous malformations type 3, respectively. Cases 5-9 were clinically and genetically diagnosed as COL9A1 gene-related multiple epiphyseal dysplasia type 6 combined with NF1 gene-related neurofibromatosis type 1, COL6A3 gene-related Bethlem myopathy with WNT1 gene-related osteogenesis imperfecta type XV, Turner syndrome (45, X0/46, XX chimera) with TH gene-related Segawa syndrome, Chromosome 22q11.2 microduplication syndrome with DYNC1H1 gene-related autosomal dominant lower extremity-predominant spinal muscular atrophy-1, and ANKRD11 gene-related KBG syndrome combined with IRF2BPL gene-related neurodevelopmental disorder with regression, abnormal movement, language loss and epilepsy. DMD was the most common, and there were 6 autosomal dominant diseases caused by de novo heterozygous pathogenic variations. Conclusions: Pediatric patients with coexistence of double genetic diagnoses show complex phenotypes. When the clinical manifestations and progression are not fully consistent with the diagnosed rare genetic disease, a second rare genetic disease should be considered, and autosomal dominant diseases caused by de novo heterozygous pathogenic variation should be paid attention to. Trio-based whole-exome sequencing combining a variety of molecular genetic tests would be helpful for precise diagnosis.
Humans ; Abnormalities, Multiple ; Retrospective Studies ; Intellectual Disability/genetics* ; Bone Diseases, Developmental/complications* ; Tooth Abnormalities/complications* ; Facies ; Muscular Dystrophy, Duchenne/complications* ; Muscular Atrophy, Spinal/complications* ; Carrier Proteins ; Nuclear Proteins

OBJECTIVE: To explore the clinical and genetic characteristics of three children with KBG syndrome. METHODS: Clinical data of the three children from two families who have presented at the First Affiliated Hospital of Zhengzhou University between October 2019 and September 2020 and their family members were collected. Trio-whole exome sequencing (trio-WES) and Sanger sequencing were carried out. RESULTS: All children had feeding difficulties, congenital heart defects and facial dysmorphism. The sib- pair from family 1 was found to harbor a novel de novo heterozygous c.6270delT (p.Q2091Rfs*84) variant of the ANKRD11 gene, whilst the child from family 2 was found to harbor a novel heterozygous c.6858delC (p.D2286Efs*51) variant of the ANKRD11 gene, which was inherited from his mother who had a mild clinical phenotype. CONCLUSION The heterozygous frameshift variants of the ANKRD11 gene probably underlay the disease in the three children. Above findings have enriched the spectrum of the ANKRD11 gene variants.
Female ; Child ; Humans ; Abnormalities, Multiple/genetics* ; Intellectual Disability/genetics* ; Bone Diseases, Developmental/genetics* ; Tooth Abnormalities/genetics* ; Facies ; Repressor Proteins/genetics* ; Mothers ; Mutation

OBJECTIVE: To evaluate the characteristics of severe periodontitis with various number of tooth loss during 4-year natural progression, and to analyze the factors related to higher rate of tooth loss. METHODS: A total of 217 patients aged 15 to 44 years with severe periodontitis were included, who participated in a 4-year natural progression research. Data obtained from questionnaire survey, clinical examination and radiographic measurement. Tooth loss during 4-year natural progression was evaluated. The baseline periodontal disease related and caries related factors were calculated, including number of teeth with bone loss > 50%, number of missing molars, number of teeth with widened periodontal ligament space (WPDL), number of teeth with periapical lesions and etc. Characteristics of populations with various number of tooth loss and the related factors that affected higher rate of tooth loss were analyzed. RESULTS: In 4 years of natural progression, 103 teeth were lost, and annual tooth loss per person was 0.12±0.38. Nine patients lost 3 or more teeth. Thirty-four patients lost 1 or 2 teeth, and 174 patients were absent of tooth loss. Molars were mostly frequent to lose, and canines presented a minimum loss. The number of teeth with WPDL, with periapical lesions, with intrabony defects, with probing depth (PD)≥7 mm, with PD≥5 mm, with clinical attachment loss≥5 mm, with bone loss > 50% and with bone loss > 65% were positively correlated to number of tooth loss. Results from orderly multivariate Logistic regression showd that the number of teeth with bone loss > 50% OR=1.550), baseline number of molars lost (OR=1.774), number of teeth with WPDL (1 to 2: OR=1.415; ≥3: OR=13.105), number of teeth with periapical lesions (1 to 2: OR=4.393; ≥3: OR=9.526) and number of teeth with caries/residual roots (OR=3.028) were significant risk factors related to higher likelihood of tooth loss and multiple tooth loss. CONCLUSION In 4 years of natural progression, the number of teeth with bone loss > 50%, baseline number of missing molars, number of teeth with WPDL, baseline number of teeth with periapical lesions and number of teeth with caries/residual roots were significantly related to higher risk of tooth loss and multiple tooth loss among Chinese young and middle-aged patients with severe periodontitis in rural areas.
Humans ; Tooth Loss/etiology* ; Periodontitis/complications* ; Tooth ; Periodontal Diseases ; Molar

2018 international classification of periodontal and implant diseases relates the classifications with the approaches of prevention and treatment based on the stages and grades of disease. European Federation of Periodontology (EFP) evaluated the available evidences following the methodological guidance of the Association of Scientific Medical Societies in Germany and the Grading of Recommendations Assessment, Development and Evaluation (GRADE), and published the EFP S3 level clinical practice guideline for the treatment of stage Ⅰ-Ⅲ and Ⅳ periodontitis in 2020 and 2022, respectively. The present manuscript gives introduction and interpretation based on the EFP S3 level clinical practice guideline and Chinese national conditions. On the base of the diagnostic key points of staging and grading, it introduces in detail the step treatment procedures of stageⅠ-Ⅲ periodontitis as well as the multi-disciplinary treatment procedures of stage Ⅳ periodontitis, compares the similarities and differences between the step and phase procedures, and then proposes a strategy for determining the recall interval more suitable for Chinese clinicians. The present manuscript aims to help dentists to learn and grasp the key points more quickly and accurately on the clinical application of the guideline and to assist them in making the optimal treatment plans after judging and evaluating the specific clinical circumstances, so as to maximize the chances of favorable outcome.
Humans ; Periodontal Diseases/therapy* ; Periodontics ; Periodontitis/therapy* ; Tooth

OBJECTIVE: To summarize the clinical phenotype and genotypic characteristics of 3 patients with KBG syndrome and epileptic seizure. METHODS: Clinical data of the patients were collected. Family-trio whole exon sequencing (WES) was carried out. Candidate variants were verified by Sanger sequencing. RESULTS: Patients 1 and 2 were boys, and patient 3 was an adult woman. All patients had epileptic seizures and mental deficiency. Their facial features included triangular face, low hair line, hypertelorism, large forward leaning auricles, broad nasal bridge, upturned nostrils, long philtrum, arched upper lip, and macrodontia. The two boys also had bilateral Simian creases. WES revealed that the three patients all harbored heterozygous de novo frameshift variants in exon 9 of the ANKRD11 gene including c.2948delG (p.Ser983Metfs*335), c.5397_c.5398insC (p.Glu1800Argfs*150) and c.1180_c.1184delAATAA (p.Asn394Hisfs*42). So far 291 patients with ANKRD11 gene variants or 16q24.3 microdeletions were reported, with over 75% being de novo mutations. CONCLUSION Above findings have enriched the spectrum of ANKRD11 gene mutations underlying KBG syndrome. WES is helpful for the early diagnosis of KBG, and provided reference for genetic counseling of this disease.
Abnormalities, Multiple/genetics* ; Bone Diseases, Developmental/genetics* ; Epilepsy/genetics* ; Facies ; Humans ; Intellectual Disability/genetics* ; Phenotype ; Repressor Proteins/genetics* ; Seizures/genetics* ; Tooth Abnormalities/genetics*

ABSTRACT Orofacial odontogenic infection, although arises from dental origin, can extend into the facial spaces and lead to debilitating complications. This study analysed the clinical pattern and management of orofacial odontogenic infection in a tertiary hospital namely Hospital Raja Permaisuri Bainun in Perak, Malaysia. We investigated any associations between socio-demographic factors, diabetic, comorbidities, smoking, pregnancy, antibiotic resistance, number and type of space infected towards prolonged hospital stay. All adult patients with orofacial odontogenic infections treated by Department of Oral and Maxillofacial Surgery from 2014 to 2018 were included. Clinical patterns were evaluated. Statistical analysis was performed to measure various variables towards prolonged hospital stay. A total of 154 patients (78 male, 76 female) were included in this study with mean age of 37.95 ± 14.9 years. Key factors of orofacial odontogenic infection requiring admissions were swelling, pain, trismus, odynophagia, reduced oral intake, raised floor of mouth and dyspnea. Among inpatients, three factors were significantly associated with prolonged hospital stay, namely antibiotic resistance, multiple space and secondary space infection. Local prevalence data was reported. Pus culture and sensitivity tests were recommended for all inpatients with multiple space and secondary space involvement, in order to rule out antibiotic resistance and to improve recovery rate.
Tooth Diseases

OBJECTIVE: To explore gender difference in the clinical manifestations of two children with Keishi-Bukuryo-Gan syndrome (KBGS). METHODS: Clinical manifestations of the two children were reviewed. Genetic testing was carried out through next generation sequencing (NGS). Treatment was summarized, and the prognosis was followed up. RESULTS: Both children showed particular appearance including megatooth, abnormal hair distribution, hands' abnormality and language development delay. NGS revealed that both children have carried pathogenic variants of the ANKRD11 gene (c.1903_1907del and c.4911delT), which resulted in shifting of amino acid sequences starting from the Lysine and Proline at positions 635 and 1638, respectively. The female patient exhibited central precocious puberty. Her height has increased by 13 cm, and sex characteristics has retracted after treatment with leuprorelin for 23 months and recombinant human growth hormone for 1 month. CONCLUSION Comparison of the two cases with different genders and summary of previously reported cases found that male KBGS patients have more obvious dysmorphisms such as triangular face, synophrys, ocular hypertelorism and vertebral body abnormality, with higher morbidity of epilepsy, mental retardation, autism, congenital heart disease, immune thrombocytopenia and other complications. KBGS is an autosomal dominant disease featuring more evident peculiar appearance and global development delay. Male patients often have multi-system involvement, and multidisciplinary cooperation is required for early recognition of particular features in order to improve the prognosis.
Abnormalities, Multiple ; Bone Diseases, Developmental ; Child ; Facies ; Female ; Humans ; Intellectual Disability ; Male ; Phenotype ; Repressor Proteins/genetics* ; Sex Characteristics ; Tooth Abnormalities

Considering the adverse effects of nonimpacted third molars (N-M3s) on the periodontal health of adjacent second molars (M2s), the removal of N-M3s may be beneficial to the periodontal health of their neighbors. This study aimed to investigate the clinical, immunological, and microbiological changes of the periodontal condition around M2s following removal of neighboring N-M3s across a 6-month period. Subjects with at least one quadrant containing an intact first molar (M1), M2, and N-M3 were screened and those who met the inclusion criteria and decided to receive N-M3 extraction were recruited in the following investigation. M2 periodontal condition was interrogated before M3 extraction (baseline) and at 3 and 6 months postoperatively. Improvements in clinical periodontal indexes of M2s in response to their adjacent N-M3 removal, along with changes in inflammatory biomarkers among gingival crevicular fluid (GCF) and the composition of subgingival plaque collected from the distal sites of the M2s of the targeted quadrant were parallelly analyzed. Complete data of 26 tooth extraction patients across the follow-up period were successfully obtained and subsequently applied for statistical analysis. Compared to the baseline, the periodontal condition of M2s was significantly changed 6 months after N-M3 removal; specifically, the probing depth of M2s significantly reduced (P < 0.001), the matrix metalloproteinase (MMP)-8 concentration involved in GCF significantly decreased (P = 0.025), and the abundance of the pathogenic genera unidentified Prevotellaceae and Streptococcus significantly decreased (P < 0.001 and P = 0.009, respectively). We concluded that N-M3 removal was associated with superior clinical indexes, decreased GCF inflammatory biomarkers, and reduced pathogenic microbiome distribution within the subgingival plaque. Although the retention or removal of N-M3s continues to be controversial, our findings provide additional evidence that medical decisions should be made as early as possible or at least before the neighboring teeth are irretrievably damaged.
Humans ; Molar/surgery* ; Molar, Third/surgery* ; Periodontal Diseases ; Periodontal Index ; Tooth Extraction

Pulpal and periapical diseases are the most prevalent dental conditions damaging the oral health of children in China. In view of China's national condition, the level of diagnosis and treatment for pulpal and periapical diseases of deciduous teeth is uneven and clinically there are inconsistent standards on the selection of operation methods for the endodontic treatment in deciduous teeth. Targeting these problems, the Society of Pediatric Dentistry, Chinese Stomatological Association organized experts from several famous universities and hospitals in China to carry out a panel discussion. The results of domestic and overseas researches and diagnosis and treatment experiences on dental pulp disease and periapical disease of deciduous teeth were also referred to. The present guideline was finally developed for the reference of dental clinicians.
Child ; Dental Care ; Dental Pulp ; Dental Pulp Necrosis ; Humans ; Periapical Diseases ; Tooth, Deciduous

OBJECTIVE: To explore the genetic basis for a pedigree affected with Nance-Horan syndrome. METHODS: Clinical manifestation of the patients was analyzed. Genomic DNA was extracted from peripheral blood samples of the pedigree members and 100 unrelated healthy controls. A panel of genes for congenital cataract was subjected to next-generation sequencing (NGS), and candidate variant was verified by Sanger sequencing and bioinformatic analysis based on guidelines of American College of Medical Genetics and Genomics (ACMG). mRNA expression was determined by reverse transcriptase-PCR (RT-PCR). Linkage analysis based on short tandem repeats was carried out to confirm the consanguinity. RESULTS: A small insertional variant c.766dupC (p.Leu256Profs*21) of the NHS gene was identified in the proband and his affected mother, but not among unaffected members and the 100 healthy controls. The variant was unreported in Human Gene Mutation Database (HGMD) and other databases. Based on the ACMG guideline, the variant is predicted to be pathogenic (PVS1+PM2+PM6+PP4). CONCLUSION The novel variant c.766dupC of the NHS gene probably underlay the X-linked dominant Nance-Horan syndrome in this pedigree.
Cataract/genetics* ; Genetic Diseases, X-Linked ; Humans ; Mutation ; Pedigree ; State Medicine ; Tooth Abnormalities