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Journal of Ultrasound in Medicine :... Mar 2024To prospectively evaluate the prognosis of fetuses diagnosed with micrognathia using prenatal ultrasound screening.
OBJECTIVE
To prospectively evaluate the prognosis of fetuses diagnosed with micrognathia using prenatal ultrasound screening.
METHODS
Between January 2019 and December 2022, a normal range of IFA to evaluate the facial profile in fetuses with micrognathia in a Chinese population between 11 and 20 gestational weeks was established, and the pregnancy outcomes of fetal micrognathia were described. The medical records of these pregnancies were collected, including family history, maternal demographics, sonographic findings, genetic testing results, and pregnancy outcomes.
RESULTS
Ultrasound identified 25 patients with fetal micrognathia, with a mean IFA value of 43.6°. All cases of isolated fetal micrognathia in the initial scans were non-isolated in the following scans. A total of 78.9% (15/19) cases had a genetic cause confirmed, including 12 with chromosomal abnormalities and 3 with monogenic disorders. Monogenic disorders were all known causes of micrognathia, including two cases of campomelic dysplasia affected by SOX9 mutations and one case of mandibulofacial dysostosis with an EFTUD2 mutation. In the end, 19 cases were terminated, 1 live birth was diagnosed as Pierre Robin syndrome, and 5 cases were lost to follow-up.
CONCLUSION
IFA is a useful indicator and three-dimensional ultrasound is a significant support technique for fetal micrognathia prenatal diagnosis. Repeat ultrasound monitoring and genetic testing are crucial, with CMA recommended and Whole exome sequencing performed when normal arrays are reported. Isolated fetal micrognathia may be an early manifestation of monogenic disorders.
Topics: Pregnancy; Female; Humans; Micrognathism; Prospective Studies; Ultrasonography, Prenatal; Prenatal Diagnosis; Fetus; Peptide Elongation Factors; Ribonucleoprotein, U5 Small Nuclear
PubMed: 38164991
DOI: 10.1002/jum.16379 -
The Journal of Craniofacial Surgery Jun 2024The aim of this cross-sectional study was to evaluate, via cone-beam computed tomography, the long-term postoperative outcome in children treated with mandibular...
AIM
The aim of this cross-sectional study was to evaluate, via cone-beam computed tomography, the long-term postoperative outcome in children treated with mandibular distraction osteogenesis.
MATERIALS AND METHODS
All young patients treated with mandibular distraction osteogenesis (MDO), during a 16-year period, at the University Department of Oral and Maxillofacial Surgery of a Pediatric Hospital, were recalled, and various clinical and radiographic parameters were recorded.
RESULTS
Eleven patients were included: 5 with hemifacial microsomia (HFM) and 6 with mandibular micrognathia. In all cases, MDO had been successful in regular follow-up and decannulation, soon after MDO, was achieved in all tracheostomy cases. The long-term result in cases of HFM was found stable, functionally and esthetically accepted, although less satisfactory than in regular follow-up; in micrognathia patients, relapse of different degrees was registered in 4 of 6 cases, without any need for tracheostomy though. Detailed and accurate information was obtained by cone-beam computed tomography (CBCT). The shape of the regenerated bone was irregular in HFM cases and relatively normal in the micrognathia cases. Quality of the regenerated bone was normal in all patients. The irregular shape registered in HFM cases did not compromise a safe orthognathic operation.
CONCLUSIONS
Distraction osteogenesis remains an early treatment choice in cases of mandibular deformities. Long-term findings showed that there is a degree of relapse with growth, which was more obvious in mandibular micrognathia cases. Computed tomography contributes to detailed evaluation of changes at the distraction site.
Topics: Humans; Osteogenesis, Distraction; Cone-Beam Computed Tomography; Female; Child; Male; Adolescent; Cross-Sectional Studies; Mandible; Treatment Outcome; Micrognathism; Facial Asymmetry; Child, Preschool
PubMed: 38376164
DOI: 10.1097/SCS.0000000000010044 -
Molecular Genetics & Genomic Medicine Apr 2024Auriculocondylar syndrome (ARCND) is a rare congenital craniofacial developmental malformation syndrome of the first and second pharyngeal arches with external ear... (Review)
Review
BACKGROUND
Auriculocondylar syndrome (ARCND) is a rare congenital craniofacial developmental malformation syndrome of the first and second pharyngeal arches with external ear malformation at the junction between the lobe and helix, micromaxillary malformation, and mandibular condylar hypoplasia. Four subtypes of ARCND have been described so far, that is, ARCND1 (OMIM # 602483), ARCND2 (ARCND2A, OMIM # 614669; ARCND2B, OMIM # 620458), ARCND3 (OMIM # 615706), and ARCND4 (OMIM # 620457).
METHODS
This study reports a case of ARCND2 resulting from a novel pathogenic variant in the PLCB4 gene, and summarizes PLCB4 gene mutation sites and phenotypes of ARCND2.
RESULTS
The proband, a 5-day-old male neonate, was referred to our hospital for respiratory distress. Micrognathia, microstomia, distinctive question mark ears, as well as mandibular condyle hypoplasia were identified. Trio-based whole-exome sequencing identified a novel missense variant of NM_001377142.1:c.1928C>T (NP_001364071.1:p.Ser643Phe) in the PLCB4 gene, which was predicted to impair the local structural stability with a result that the protein function might be affected. From a review of the literature, only 36 patients with PLCB4 gene mutations were retrieved.
CONCLUSION
As with other studies examining familial cases of ARCND2, incomplete penetrance and variable expressivity were observed within different families' heterozygous mutations in PLCB4 gene. Although, motor and intellectual development are in the normal range in the vast majority of patients with ARCND2, long-term follow-up and assessment are still required.
Topics: Humans; Infant, Newborn; Male; China; Ear; Ear Diseases; Micrognathism; Phospholipase C beta; East Asian People
PubMed: 38618928
DOI: 10.1002/mgg3.2441 -
International Journal of Oral and... Jan 2024Helical mandibular distraction is theoretically better than linear or circular distraction. However, it is not known whether this more complex treatment will result in...
Helical mandibular distraction is theoretically better than linear or circular distraction. However, it is not known whether this more complex treatment will result in unquestionably better outcomes. Therefore, the best attainable outcomes of mandibular distraction osteogenesis were evaluated in silico, given the constraints of linear, circular, and helical motion. This cross-sectional kinematic study included 30 patients with mandibular hypoplasia who had been treated with distraction, or to whom this treatment had been recommended. Demographic information and the computed tomography (CT) scans showing the baseline deformity were collected. The CT scans of each patient were segmented and three-dimensional models of the face created. Then, the ideal distraction outcomes were simulated. Next, the most favorable helical, circular, and linear distraction movements were calculated. Finally, errors were measured: misalignment of key mandibular landmarks, misalignment of the occlusion, and changes in intercondylar distance. Helical distraction produced trivial errors. In contrast, circular and linear distractions resulted in errors that were statistically and clinically significant. Helical distraction also preserved the planned intercondylar distance, while circular and linear distractions led to unwanted changes in the intercondylar distance. It is now evident that helical distraction offers a new strategy to improve the outcomes of mandibular distraction osteogenesis.
Topics: Humans; Osteogenesis, Distraction; Cross-Sectional Studies; Facial Asymmetry; Mandible; Micrognathism
PubMed: 37277242
DOI: 10.1016/j.ijom.2023.04.006 -
Journal of Clinical Sleep Medicine :... Jan 2024In growing children, temporomandibular joint (TMJ) ankylosis and septic arthritis are uncommon. Retrognathia and micrognathia affect airway patency and can cause...
UNLABELLED
In growing children, temporomandibular joint (TMJ) ankylosis and septic arthritis are uncommon. Retrognathia and micrognathia affect airway patency and can cause obstructive sleep apnea (OSA). No unified diagnostic criteria have been established for the management of this pathology. We describe the first case of treatment for pediatric TMJ ankylosis and severe OSA due to neonatal group B streptococcal septic TMJ arthritis. Untreated pathological changes in the TMJ will eventually lead to ankylosis. Among children, this will include facial growth disturbances leading to mandibular retrognathia, reduction in the oropharyngeal spaces, and OSA. Our patient had severe OSA with an apnea-hypopnea index of 24.9 events/h and oxygen saturation nadir of 73% as measured by polysomnography. She was treated successfully according to Andrade protocol. This is the first report of pediatric OSA due to TMJ ankylosis following neonatal group B streptococcal septic arthritis.
CITATION
Pesis M, Goldbart A, Givol N. Surgical correction of neonatal obstructive sleep apnea due to a temporomandibular joint ankylosis. . 2024;20(1):173-179.
Topics: Female; Infant, Newborn; Humans; Child; Mandible; Retrognathia; Osteogenesis, Distraction; Sleep Apnea, Obstructive; Micrognathism; Ankylosis; Temporomandibular Joint; Arthritis, Infectious
PubMed: 37811905
DOI: 10.5664/jcsm.10856 -
Zhonghua Yi Xue Yi Chuan Xue Za Zhi =... Jan 2024To explore the genetic basis of two children with unexplained psychomotor developmental delay and facial dysmorphisms suggestive of Coffin-Siris syndrome (CSS).
OBJECTIVE
To explore the genetic basis of two children with unexplained psychomotor developmental delay and facial dysmorphisms suggestive of Coffin-Siris syndrome (CSS).
METHODS
A boy and a girl suspected for CSS at the 980th Hospital of the People's Liberation Army Joint Service Support Force respectively in July 2019 and January 2021, and seven members from their families, were selected as the study subjects. Clinical data and family history of the children were collected, and detailed physical examination was carried out, in addition with laboratory and related auxiliary examinations. Potential variants and copy number variations (CNVs) were detected by whole exome sequencing (WES) and copy number variation sequencing (CNV-seq).
RESULTS
Child 1, an 8-month-old female, had featured microcephaly, atrial septal defect, curving of fifth finger/toe, and low limb muscle tone. Child 2 was a 2.5-year-old male with language delay, social impairment, dense hair but no curving of the fifth fingers. Genetic testing revealed that child 1 had loss of heterozygosity for exons 8 to 21 of the ARID1B gene, which was unreported previously. Family verification showed that both of her parents were of the wild type. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and American Society of Molecular Pathology (AMP), the variant was rated as pathogenic (PVS1+PS2+PM2-supporting). Child 2 was found to harbor a heterozygous c.4263-6 (IVS17) T>G variant of the ARID1B gene. Transcriptome sequencing confirmed that the variant can affect the normal splicing, resulting in retention of a 5 bp sequence in intron 17. Family verification showed that both of his parents were of the wild type. Based on the guidelines from the ACMG, the variant was rated as pathogenic (PS2+PM2-supporting+PP3+PS3).
CONCLUSION
WES and RNA-seq have confirmed the diagnosis of CSS in both children. Discovery of the novel variants has expanded the spectrum of pathogenic mutations underlying CSS, and provided a basis for the genetic counseling.
Topics: Child, Preschool; Female; Humans; Infant; Male; Abnormalities, Multiple; DNA Copy Number Variations; DNA-Binding Proteins; Intellectual Disability; Micrognathism; Mutation; Transcription Factors
PubMed: 38171562
DOI: 10.3760/cma.j.cn511374-20221026-00721 -
Clinical Oral Investigations Apr 2024Coffin-Siris Syndrome (CSS) is a congenital disorder characterized by delayed growth, dysmorphic facial features, hypoplastic nails and phalanges of the fifth digit, and...
OBJECTIVES
Coffin-Siris Syndrome (CSS) is a congenital disorder characterized by delayed growth, dysmorphic facial features, hypoplastic nails and phalanges of the fifth digit, and dental abnormalities. Tooth agenesis has been reported in CSS patients, but the mechanisms regulating this syndromic tooth agenesis remain largely unknown. This study aims to identify the pathogenic mutation of CSS presenting tooth genesis and explore potential regulatory mechanisms.
MATERIALS AND METHODS
We utilized whole-exome sequencing to identify variants in a CSS patient, followed by Sanger validation. In silico analysis including conservation analysis, pathogenicity predictions, and 3D structural assessments were carried out. Additionally, single-cell RNA sequencing and fluorescence in situ hybridization (FISH) were applied to explore the spatio-temporal expression of Sox4 expression during murine tooth development. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to examine the functional role of SOX4.
RESULTS
A novel de novo SOX4 missense mutation (c.1255C > G, p.Leu419Val) was identified in a Chinese CSS patient exhibiting tooth agenesis. Single-cell RNA sequencing and FISH further verified high expression of Sox4 during murine tooth development, and WGCNA confirmed its central role in tooth development pathways. Enriched functions included cell-substrate junctions, focal adhesion, and RNA splicing.
CONCLUSIONS
Our findings link a novel SOX4 mutation to syndromic tooth agenesis in CSS. This is the first report of SOX4 missense mutation causing syndromic tooth agenesis.
CLINICAL RELEVANCE
This study not only enhances our understanding of the pathogenic mutation for syndromic tooth agenesis but also provides genetic diagnosis and potential therapeutic insights for syndromic tooth agenesis.
Topics: Animals; Female; Humans; Male; Mice; Abnormalities, Multiple; Anodontia; Exome Sequencing; Face; Hand Deformities, Congenital; In Situ Hybridization, Fluorescence; Intellectual Disability; Micrognathism; Mutation, Missense; Neck; SOXC Transcription Factors
PubMed: 38684576
DOI: 10.1007/s00784-024-05659-6 -
Journal of Cranio-maxillo-facial... Jan 2024The study aimed to evaluate the mid-term effect of MDO in children with Robin sequence (RS). In this case series, 13 patients with RS who underwent MDO were followed up...
The study aimed to evaluate the mid-term effect of MDO in children with Robin sequence (RS). In this case series, 13 patients with RS who underwent MDO were followed up for more than 5 years. Data were collected using clinical history and physical examination. Polysomnography was performed and endoscopic evaluations of the airway was performed if patients still presented obstructive signs of upper airways and/or dysphagia. The patients' clinical signs improved in the mid-term after versus before MDO (inspiratory noise, 92,3% vs 30,8%; apnea, 84,6% vs 7,7%; cyanosis, 76,9% vs 0%; desaturations, 69,2% vs 0%; and suprasternal/intercostal retractions, 61,5% vs 0%; p < 0.05). Statistically significant improvement was noted in the following polysomnographic parameters evaluated in the pre and postoperative mid-term: apnea-hypopnea index, total sleep time and desaturation index (p < 0.05). Within the limitations of the study it seems that MDO is an effective surgical option for children with RS, not only in the short term as previously demonstrated, but also in the mid-term.
Topics: Child; Humans; Infant; Polysomnography; Retrospective Studies; Pierre Robin Syndrome; Osteogenesis, Distraction; Apnea; Treatment Outcome; Mandible; Airway Obstruction
PubMed: 37884434
DOI: 10.1016/j.jcms.2023.08.004 -
Congenital Anomalies Nov 2023
Topics: Pregnancy; Female; Humans; Hernias, Diaphragmatic, Congenital; Pregnancy Trimester, First; Exome Sequencing; Intellectual Disability; Micrognathism; Hand Deformities, Congenital; Neck; Prenatal Diagnosis; Abnormalities, Multiple; Face
PubMed: 37538046
DOI: 10.1111/cga.12535 -
The Journal of Pediatrics Feb 2024To describe the spectrum of disease and burden of care in infants with congenital micrognathia from a multicenter cohort hospitalized at tertiary care centers.
OBJECTIVE
To describe the spectrum of disease and burden of care in infants with congenital micrognathia from a multicenter cohort hospitalized at tertiary care centers.
STUDY DESIGN
The Children's Hospitals Neonatal Database was queried from 2010 through 2020 for infants diagnosed with micrognathia. Demographics, presence of genetic syndromes, and cleft status were summarized. Outcomes included death, length of hospitalization, neonatal surgery, and feeding and respiratory support at discharge.
RESULTS
Analysis included 3,236 infants with congenital micrognathia. Cleft palate was identified in 1266 (39.1%). A genetic syndrome associated with micrognathia was diagnosed during the neonatal hospitalization in 256 (7.9%). Median (IQR) length of hospitalization was 35 (16, 63) days. Death during the hospitalization (n = 228, 6.8%) was associated with absence of cleft palate (4.4%, P < .001) and maternal Black race (11.6%, P < .001). During the neonatal hospitalization, 1289 (39.7%) underwent surgery to correct airway obstruction and 1059 (32.7%) underwent gastrostomy tube placement. At the time of discharge, 1035 (40.3%) were exclusively feeding orally. There was significant variability between centers related to length of stay and presence of a feeding tube at discharge (P < .001 for both).
CONCLUSIONS
Infants hospitalized with congenital micrognathia have a significant burden of disease, commonly receive surgical intervention, and most often require tube feedings at hospital discharge. We identified disparities based on race and among centers. Development of evidence-based guidelines could improve neonatal care.
Topics: Infant; Child; Humans; Infant, Newborn; Micrognathism; Cleft Palate; Airway Obstruction; Intensive Care Units; North America; Retrospective Studies
PubMed: 37879601
DOI: 10.1016/j.jpeds.2023.113799