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Journal of Human Genetics Sep 2019Micrognathia is a common craniofacial deformity which represents hypoplastic development of the mandible, accompanied by retrognathia and consequent airway problems....
Micrognathia is a common craniofacial deformity which represents hypoplastic development of the mandible, accompanied by retrognathia and consequent airway problems. Usually, micrognathia is accompanied by multiple systematic defects, known as syndromic micrognathia, and is in close association with genetic factors. Now, large quantities of pathogenic genes of syndromic micrognathia have been revealed. However, how these different pathogenic genes could lead to similar phenotypes, and whether there are some common characteristics among these pathogenic genes are still unknown. In this study, we proposed a genetic-phenotypic classification of syndromic micrognathia based on pathogenic genes information obtained from Phenolyzer, DAVID, OMIM, and PubMed database. Pathogenic genes of syndromic micrognathia could be divided into four groups based on gene function, including cellular processes and structures, cell metabolism, cartilage and bone development, and neuromuscular function. In addition, these four groups exhibited various clinical characteristics, and the affected systems, such as central nervous system, skeletal system, cardiovascular system, oral and dental system, respiratory system and muscle, were different in these four groups. This classification could provide meaningful insights into the pathogenesis of syndromic micrognathia, and offer some clues for understanding the molecular mechanism, as well as guiding precise clinical diagnosis and treatment for syndromic micrognathia.
Topics: Humans; Mandible; Micrognathism; Phenotype; Syndrome
PubMed: 31273320
DOI: 10.1038/s10038-019-0630-4 -
American Journal of Medical Genetics.... Sep 2014Recently, de novo aberrations in PHF6 were identified in females with intellectual disability and with a distinct phenotype including a characteristic facial gestalt... (Review)
Review
Recently, de novo aberrations in PHF6 were identified in females with intellectual disability and with a distinct phenotype including a characteristic facial gestalt with bitemporal narrowing, prominent supraorbital ridges, synophrys, a short nose and dental anomalies, tapering fingers with brachytelephalangy, clinodactyly and hypoplastic nails, short toes with hypoplastic nails, and linear skin hyperpigmentation. In adolescent or older patients, this phenotype overlaps but is not identical with Borjeson-Forssman-Lehmann syndrome in males, caused by X-linked recessive mutations in PHF6. In younger girls there seems to be a striking phenotypic overlap with Coffin-Siris syndrome, which is characterized by intellectual disability, sparse hair and hypoplastic nails. This review will summarize and characterize the female phenotype caused by de novo aberrations in PHF6 and will discuss the overlapping and distinguishing features with Coffin-Siris syndrome.
Topics: Abnormalities, Multiple; Carrier Proteins; Child; Epilepsy; Face; Female; Fingers; Genetic Association Studies; Growth Disorders; Hand Deformities, Congenital; Humans; Hypogonadism; Intellectual Disability; Mental Retardation, X-Linked; Micrognathism; Nails, Malformed; Neck; Obesity; Pedigree; Repressor Proteins; Young Adult
PubMed: 25099957
DOI: 10.1002/ajmg.c.31408 -
Bone Feb 2024Arthrogryposis multiplex congenita (AMC) is a heterogeneous group of disorders associated with decreased fetal movement, with a prevalence between 1/3000 and 1/5200 live... (Review)
Review
INTRODUCTION
Arthrogryposis multiplex congenita (AMC) is a heterogeneous group of disorders associated with decreased fetal movement, with a prevalence between 1/3000 and 1/5200 live births. Typical features of AMC include multiple joint contractures present at birth, and can affect all joints of the body, from the jaw, and involving the upper limbs, lower limbs and spine. The jaws may be affected in 25 % of individuals with AMC, with limited jaw movement and mouth opening. Other oral and maxillofacial deformities may be present in AMC, including cleft palate, micrognathia, periodontitis and delayed teething. To our knowledge, oral and maxillofacial abnormalities have not been systematically assessed in individuals with AMC. Therefore, this scoping review was conducted to identify, collect, and describe a comprehensive map of the existing knowledge on dental and maxillofacial involvement in individuals with AMC.
METHODOLOGY
A scoping review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines. The PRISMA guidelines for scoping reviews were followed and databases were searched for empirical articles in English and French published until October 2022. We searched MEDLINE, Embase, Web of Science and ERIC databases. Two authors independently reviewed the articles and extracted the data.
RESULTS
Of a total of 997 studies that were identified, 96 met the inclusion criteria and were subsequently included in this scoping review. These 96 studies collectively provided insights into 167 patients who exhibited some form of oral and/or maxillofacial involvement. Notably, 25 % of these patients were within the age range of 0-6 months. It is worth highlighting that only 22 out of the 96 studies (22.9 %), had the primary objective of evaluating dental and/or maxillofacial deformities. Among the patients studied, a prevalent pattern emerged, revealing that severe anomalies such as micrognathia (56 %), high-arched palate (29 %), cleft palate (40 %), limited mouth opening (31 %), and dental anomalies (28 %) were frequently observed. Importantly, many of these patients were found to have more than one of these anomalies. Even though these maxillofacial impairments are known to be associated with dental problems (e.g., cleft palate is associated with oligodontia, hypodontia, and malocclusion), their secondary effects on the dental phenotype were not reported in the studies.
CONCLUSION
Our findings have uncovered a notable deficiency in existing literature concerning dental and maxillofacial manifestations in AMC. This underscores the need for interdisciplinary collaboration and the undertaking of extensive prospective cohort studies focused on AMC. These studies should assess the oral and maxillofacial abnormalities that can impact daily functioning and overall quality of life.
Topics: Infant, Newborn; Humans; Infant; Arthrogryposis; Cleft Palate; Micrognathism; Prospective Studies; Quality of Life
PubMed: 37951521
DOI: 10.1016/j.bone.2023.116955 -
BMJ Case Reports Jan 2021We report a child, diagnosed with Coffin-Siris syndrome (CSS), with chronic right otorrhoea. CT and DR-MRI were performed to further investigate, diagnose and determine...
We report a child, diagnosed with Coffin-Siris syndrome (CSS), with chronic right otorrhoea. CT and DR-MRI were performed to further investigate, diagnose and determine relevant surgical anatomy. CT temporal bones assessment was performed, and the measurements compared with previously published data for normal temporal bone anatomy. These comparisons highlighted various differences which were not initially expected; it showed that there were multiple inner ear abnormalities in addition to middle ear disease. This case highlights the importance of considering temporal bone abnormalities in all children with CSS or any dysmorphia, when they may require mastoid procedures. Reviewing the management of this case provides relevant learning opportunities for both primary, secondary and tertiary care institutions.
Topics: Abnormalities, Multiple; Bone Diseases, Developmental; Child; Face; Hand Deformities, Congenital; Humans; Intellectual Disability; Magnetic Resonance Imaging; Male; Micrognathism; Neck; Temporal Bone; Tomography, X-Ray Computed
PubMed: 33461995
DOI: 10.1136/bcr-2020-236139 -
Clinical Genetics Nov 2015The spliceosome is a large ribonucleoprotein complex that removes introns from pre-mRNA transcripts. Mutations in EFTUD2, encoding a component of the major spliceosome,... (Review)
Review
The spliceosome is a large ribonucleoprotein complex that removes introns from pre-mRNA transcripts. Mutations in EFTUD2, encoding a component of the major spliceosome, have recently been identified as the cause of mandibulofacial dysostosis, Guion-Almeida type (MFDGA), characterized by mandibulofacial dysostosis, microcephaly, external ear malformations and intellectual disability. Mutations in several other genes involved in spliceosomal function or linked aspects of mRNA processing have also recently been identified in human disorders with specific craniofacial malformations: SF3B4 in Nager syndrome, an acrofacial dysostosis (AFD); SNRPB in cerebrocostomandibular syndrome, characterized by Robin sequence and rib defects; EIF4A3 in the AFD Richieri-Costa-Pereira syndrome, characterized by Robin sequence, median mandibular cleft and limb defects; and TXNL4A in Burn-McKeown syndrome, involving specific craniofacial dysmorphisms. Here, we review phenotypic and molecular aspects of these syndromes. Given the apparent sensitivity of craniofacial development to defects in mRNA processing, it is possible that mutations in other proteins involved in spliceosomal function will emerge in the future as causative for related human disorders.
Topics: Choanal Atresia; Clubfoot; DEAD-box RNA Helicases; Deafness; Eukaryotic Initiation Factor-4A; Facies; Female; Hand Deformities, Congenital; Heart Defects, Congenital; Humans; Intellectual Disability; Male; Mandibulofacial Dysostosis; Micrognathism; Mutation; Peptide Elongation Factors; Pierre Robin Syndrome; RNA Splicing Factors; RNA-Binding Proteins; Ribonucleoprotein, U5 Small Nuclear; Ribs; Spliceosomes
PubMed: 25865758
DOI: 10.1111/cge.12596 -
Clinical Oral Investigations Dec 2023The purpose of this study was to evaluate the 3D anatomical features of unilateral (UCLP) and bilateral (BCLP) complete cleft lip and palate with those of skeletal Class...
OBJECTIVE
The purpose of this study was to evaluate the 3D anatomical features of unilateral (UCLP) and bilateral (BCLP) complete cleft lip and palate with those of skeletal Class III dentofacial deformities.
MATERIALS AND METHODS
In total, 92 patients were divided into cleft and noncleft groups. The cleft group comprised 29 patients with UCLP and 17 patients with BCLP. The noncleft group comprised 46 patients with Class III dentofacial deformities. 3D anatomical landmarks were identified and the corresponding measurements were made on the cone-beam computed tomography (CBCT).
RESULTS
The differences between the affected and unaffected sides of the patients with UCLP were nonsignificant. The differences between the patients with UCLP and BCLP were nonsignificant except for the SNA angle. Significant differences between the patients with clefts and Class III malocclusion were identified for the SNA, A-N perpendicular, and A-N Pog line, indicating that the maxillae of the patients in the cleft group were more retrognathic and micrognathic. Relative to the noncleft group patients, the cleft group patients had a significantly smaller ramus height.
CONCLUSION
The affected and unaffected sides of the patients with UCLP did not exhibit significant differences. The maxillae of the patients with UCLP were significantly more retrognathic than those of the patients with BCLP. The maxillae and mandibles of the patients in the cleft group were more micrognathic and retropositioned relative to those of the noncleft Class III patients.
CLINICAL RELEVANCE
The maxillary and mandibular findings indicated greater deficiencies in the patients with UCLP or BCLP than in those with skeletal Class III malocclusion. Appropriate surgical design should be administered.
Topics: Humans; Cleft Lip; Cleft Palate; Dentofacial Deformities; Malocclusion, Angle Class III
PubMed: 37910241
DOI: 10.1007/s00784-023-05345-z -
Clinical Anatomy (New York, N.Y.) Apr 2024Cerebro-costo-mandibular syndrome (CCMS) is a congenital condition with skeletal and orofacial abnormalities that often results in respiratory distress in neonates. The... (Review)
Review
Cerebro-costo-mandibular syndrome (CCMS) is a congenital condition with skeletal and orofacial abnormalities that often results in respiratory distress in neonates. The three main phenotypes in the thorax are posterior rib gaps, abnormal costovertebral articulation and absent ribs. Although the condition can be lethal, accurate diagnosis, and subsequent management help improve the survival rate. Mutations in the causative gene SNRPB have been identified, however, the mechanism whereby the skeletal phenotypes affect respiratory function is not well-studied due to the multiple skeletal phenotypes, lack of anatomy-based studies into the condition and rarity of CCMS cases. This review aims to clarify the extent to which the three main skeletal phenotypes in the thorax contribute to respiratory distress in neonates with CCMS. Despite the posterior rib gaps being unique to this condition and visually striking on radiographic images, anatomical consideration, and meta-analyses suggested that they might not be the significant factor in causing respiratory distress in neonates. Rather, the increase in chest wall compliance due to the rib gaps and the decrease in compliance at the costovertebral complex was considered to result in an equilibrium, minimizing the impact of these abnormalities. The absence of floating ribs is likely insignificant as seen in the general population; however, a further absence of ribs or vestigial rib formation is associated with respiratory distress and increased lethality. Based on these, we propose to evaluate the number of absent or vestigial ribs as a priority indicator to develop a personalized treatment plan based on the phenotypes exhibited.
Topics: Infant, Newborn; Humans; Intellectual Disability; Ribs; Micrognathism; Respiratory Distress Syndrome
PubMed: 37265362
DOI: 10.1002/ca.24054 -
Journal of Oral and Maxillofacial... Jul 2016A variety of surgical protocols are available in the literature for performing mandibular distraction. This study aims to determine the ideal rate of distraction and... (Review)
Review
PURPOSE
A variety of surgical protocols are available in the literature for performing mandibular distraction. This study aims to determine the ideal rate of distraction and compare outcomes between internal and external distractors in children and infants with upper airway obstruction due to micrognathia.
PATIENTS AND METHODS
A systematic review was performed. The databases searched included PubMed, Embase, Scopus, Web of Knowledge, and gray-literature sources. The intervention was bilateral mandibular distraction for upper airway obstruction in children with clinical evidence of micrognathia or Pierre Robin sequence. The variables for comparison included distraction rates of 1 mm/d and 2 mm/d and external versus internal distractors. The outcome was successful completion of distraction. Complications also were recorded and compared. The data were analyzed by cross tabulation to calculate odds ratios.
RESULTS
Overall, 43 studies were included in the surgical outcomes analysis. The overall success rate of distraction was 95.4%. There was no statistically significant difference in success rate with distraction at 1 mm/d or 2 mm/d (P = .18). Distraction at 1 mm/d was associated with a higher rate of technical failures. External distractors had a higher failure rate than internal distractors (P = .012). Internal distractors had a lower rate of significant scarring (P = .006) and had a lower incidence of technical failures (P = .039).
CONCLUSIONS
In children younger than 12 months, distraction at a rate of 2 mm/d is safe and appears to have a similar success rate to distraction at 1 mm/d. Internal distractors have a higher success rate than external distractors and should be used when possible.
Topics: Child; Child, Preschool; Craniofacial Abnormalities; Humans; Infant; Infant, Newborn; Micrognathism; Osteogenesis, Distraction
PubMed: 26920642
DOI: 10.1016/j.joms.2016.01.049 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Aug 2023To explore the perioperative airway management and treatment of newborns with micrognathia and laryngomalacia. From January to December 2022, a total of 6 newborns with...
To explore the perioperative airway management and treatment of newborns with micrognathia and laryngomalacia. From January to December 2022, a total of 6 newborns with micrognathia and laryngomalacia were included. Preoperative laryngoscopy revealed concomitant laryngomalacia. These micrognathia were diagnosed as Pierre Robin sequences. All patients had grade Ⅱ or higher symptoms of laryngeal obstruction and required oxygen therapy or non-invasive ventilatory support. All patients underwent simultaneous laryngomalacia surgery and mandibular distraction osteogenesis. The shortened aryepiglottic folds were ablated using a low-temperature plasma radiofrequency during the operation. Tracheal intubation was maintained for 3-5 days postoperatively. Polysomnography(PSG) and airway CT examination were performed before and 3 months after the surgery. Among the 6 patients, 4 required oxygen therapy preoperatively and 2 required non-invasiveventilatory support. The mean age of patients was 40 days at surgery. The inferior alveolar nerve bundle was not damaged during the operation, and there were no signs of mandibular branch injury such as facial asymmetry after the surgery. Laryngomalacia presented as mixed type: type Ⅱ+ type Ⅲ. The maximum mandibular distraction distance was 20 mm, the minimum was 12 mm, and the mean was 16 mm. The posterior airway space increased from a preoperative average of 3.5 mm to a postoperative average of 9.5 mm. The AHI decreased from a mean of 5.65 to 0.85, and the lowest oxygen saturation increased from a mean of 78% to 95%. All patients were successfully extubated after the surgery, and symptoms of laryngeal obstruction such as hypoxia and feeding difficulties disappeared. Newborns with micrognathia and laryngomalacia have multi-planar airway obstruction. Simultaneous laryngomalacia surgery and mandibular distraction osteogenesis are safe and feasible, and can effectively alleviate symptoms of laryngeal obstruction such as hypoxia and feeding difficulties, while significantly improving the appearance of micrognathia.
Topics: Humans; Infant, Newborn; Infant; Micrognathism; Laryngomalacia; Treatment Outcome; Mandible; Airway Obstruction; Intubation, Intratracheal; Laryngeal Diseases; Osteogenesis, Distraction; Oxygen; Retrospective Studies
PubMed: 37551568
DOI: 10.13201/j.issn.2096-7993.2023.08.004 -
The Journal of Craniofacial Surgery Nov 2018Micrognathia occurs isolated and as part of entities like Robin sequence (RS). An objective measurement of mandible size and growth is needed to determine the degree of...
BACKGROUND
Micrognathia occurs isolated and as part of entities like Robin sequence (RS). An objective measurement of mandible size and growth is needed to determine the degree of micrognathia and enable a comparison of treatment outcomes. A pilot study was conducted to investigate the usability of 3-dimensional (3D) facial photogrammetry, a fast, noninvasive method, to estimate mandible size and growth in a small cohort of newborns and infants.
METHODS
Exterior mandibular volume was estimated using a tetrahedron defined by 4 facial landmarks. Twelve patients with RS with different etiologies were selected and photogrammetric images were obtained prospectively in 3 patients with RS in whom mandibular growth in the first year of life was determined. We used 3 tetrahedra defined by 6 landmarks on mandibular computed tomography (CT) scans to estimate an interior mandibular volume, which we compared to the exterior mandibular volume in 10 patients.
RESULTS
The exterior mandibular volume using 3D photography could be determined in all patients. Signature heat maps allowed visualization of facial dysmorphism in 3D; signature graphs demonstrated similarities of facial dysmorphism in patients with the same etiology and differences from those with other diagnoses and from controls. The correlation between interior (3D photogrammetry) and exterior mandibular volumes (CT imaging) was 0.8789.
CONCLUSION
The 3D facial photogrammetry delineates the general facial characteristics in patients with different syndromes involving micrognathia, and can objectively estimate mandibular volume and growth, with excellent correlation with bony measurement. It has been concluded that 3D facial photogrammetry could be a clinically effective instrument for delineating and quantifying micrognathia.
Topics: Cohort Studies; Female; Humans; Imaging, Three-Dimensional; Infant; Infant, Newborn; Male; Mandible; Micrognathism; Photogrammetry; Pierre Robin Syndrome; Pilot Projects; Tomography, X-Ray Computed
PubMed: 30320700
DOI: 10.1097/SCS.0000000000005056