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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 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 -
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 -
American Journal of Medical Genetics.... Aug 2022The phenotypic spectrum of SOX11-related Coffin-Siris syndrome (CSS) is expanding with reports of new associations. SOX11 is implicated in neurogenesis and inner ear...
The phenotypic spectrum of SOX11-related Coffin-Siris syndrome (CSS) is expanding with reports of new associations. SOX11 is implicated in neurogenesis and inner ear development. Cochlear nerve deficiency, absence or hypoplasia, is commonly associated with cochlear canal stenosis or with CHARGE syndrome, a monogenic condition that affects inner ear development. SOX11 is a transcription factor essential for neuronal identity, highly correlated with the expression of CHD7, which regulates SOX11. We present two unrelated probands, each with novel de novo SOX11 likely pathogenic variants and phenotypic manifestations of CSS including global developmental delay, growth deficiency, and hypoplastic nails. They have unilateral sensorineural hearing loss due to cochlear nerve deficiency confirmed on MRI. SOX11 is implicated in sensory neuron survival and maturation. It is highly expressed in the developing inner ear. Homozygous ablation of SOX11 in a mouse model resulted in a reduction in sensory neuron survival and decreased axonal growth. A heterozygous knockout mice model had hearing impairment with grossly normal inner ear structures like the two probands reported. We propose cochlear nerve deficiency as a new phenotypic feature of SOX11-related CSS. Magnetic resonance imaging is useful in delineating the cochlear nerve deficiency and other CSS-related brain malformations.
Topics: Abnormalities, Multiple; Animals; CHARGE Syndrome; Cochlear Nerve; Face; Hand Deformities, Congenital; Hearing Loss, Sensorineural; Intellectual Disability; Mice; Micrognathism; Neck; SOXC Transcription Factors
PubMed: 35642566
DOI: 10.1002/ajmg.a.62851 -
JCI Insight May 2022The eukaryotic CDC45/MCM2-7/GINS (CMG) helicase unwinds the DNA double helix during DNA replication. The GINS subcomplex is required for helicase activity and is,...
The eukaryotic CDC45/MCM2-7/GINS (CMG) helicase unwinds the DNA double helix during DNA replication. The GINS subcomplex is required for helicase activity and is, therefore, essential for DNA replication and cell viability. Here, we report the identification of 7 individuals from 5 unrelated families presenting with a Meier-Gorlin syndrome-like (MGS-like) phenotype associated with hypomorphic variants of GINS3, a gene not previously associated with this syndrome. We found that MGS-associated GINS3 variants affecting aspartic acid 24 (D24) compromised cell proliferation and caused accumulation of cells in S phase. These variants shortened the protein half-life, altered key protein interactions at the replisome, and negatively influenced DNA replication fork progression. Yeast expressing MGS-associated variants of PSF3 (the yeast GINS3 ortholog) also displayed impaired growth, S phase progression defects, and decreased Psf3 protein stability. We further showed that mouse embryos homozygous for a D24 variant presented intrauterine growth retardation and did not survive to birth, and that fibroblasts derived from these embryos displayed accelerated cellular senescence. Taken together, our findings implicate GINS3 in the pathogenesis of MGS and support the notion that hypomorphic variants identified in this gene impaired cell and organismal growth by compromising DNA replication.
Topics: Animals; Chromosomal Proteins, Non-Histone; Congenital Microtia; DNA Replication; Growth Disorders; Humans; Mice; Micrognathism; Minichromosome Maintenance Proteins; Patella; Saccharomyces cerevisiae
PubMed: 35603789
DOI: 10.1172/jci.insight.155648 -
International Journal of Oral Science Oct 2022Micrognathia is a severe craniofacial deformity affecting appearance and survival. Previous studies revealed that multiple factors involved in the osteogenesis of...
Micrognathia is a severe craniofacial deformity affecting appearance and survival. Previous studies revealed that multiple factors involved in the osteogenesis of mandibular bone have contributed to micrognathia, but concerned little on factors other than osteogenesis. In the current study, we found that ectopic activation of Fgf8 by Osr2-cre in the presumptive mesenchyme for masseter tendon in mice led to micrognathia, masseter regression, and the disrupted patterning and differentiation of masseter tendon. Since Myf5-cre;Rosa26R-Fgf8 mice exhibited the normal masseter and mandibular bone, the possibility that the micrognathia and masseter regression resulted directly from the over-expressed Fgf8 was excluded. Further investigation disclosed that a series of chondrogenic markers were ectopically activated in the developing Osr2-cre;Rosa26R-Fgf8 masseter tendon, while the mechanical sensing in the masseter and mandibular bone was obviously reduced. Thus, it suggested that the micrognathia in Osr2-cre;Rosa26R-Fgf8 mice resulted secondarily from the reduced mechanical force transmitted to mandibular bone. Consistently, when tenogenic or myogenic components were deleted from the developing mandibles, both the micrognathia and masseter degeneration took place with the decreased mechanical sensing in mandibular bone, which verified that the loss of mechanical force transmitted by masseter tendon could result in micrognathia. Furthermore, it appeared that the micrognathia resulting from the disrupted tenogenesis was attributed to the impaired osteogenic specification, instead of the differentiation in the periosteal progenitors. Our findings disclose a novel mechanism for mandibular morphogenesis, and shed light on the prevention and treatment for micrognathia.
Topics: Mice; Animals; Micrognathism; Masseter Muscle; Mandible; Osteogenesis
PubMed: 36257937
DOI: 10.1038/s41368-022-00196-y -
American Journal of Medical Genetics.... Sep 2023Heterozygous ARID1B variants result in Coffin-Siris syndrome. Features may include hypoplastic nails, slow growth, characteristic facial features, hypotonia,...
Heterozygous ARID1B variants result in Coffin-Siris syndrome. Features may include hypoplastic nails, slow growth, characteristic facial features, hypotonia, hypertrichosis, and sparse scalp hair. Most reported cases are due to ARID1B loss of function variants. We report a boy with developmental delay, feeding difficulties, aspiration, recurrent respiratory infections, slow growth, and hypotonia without a clinical diagnosis, where a previously unreported ARID1B missense variant was classified as a variant of uncertain significance. The pathogenicity of this variant was refined through combined methodologies including genome-wide methylation signature analysis (EpiSign), Machine Learning (ML) facial phenotyping, and LIRICAL. Trio exome sequencing and EpiSign were performed. ML facial phenotyping compared facial images using FaceMatch and GestaltMatcher to syndrome-specific libraries to prioritize the trio exome bioinformatic pipeline gene list output. Phenotype-driven variant prioritization was performed with LIRICAL. A de novo heterozygous missense variant, ARID1B p.(Tyr1268His), was reported as a variant of uncertain significance. The ACMG classification was refined to likely pathogenic by a supportive methylation signature, ML facial phenotyping, and prioritization through LIRICAL. The ARID1B genotype-phenotype has been expanded through an extended analysis of missense variation through genome-wide methylation signatures, ML facial phenotyping, and likelihood-ratio gene prioritization.
Topics: Male; Humans; DNA-Binding Proteins; Muscle Hypotonia; Transcription Factors; Face; Abnormalities, Multiple; Micrognathism; Intellectual Disability; Hand Deformities, Congenital; Neck
PubMed: 37654076
DOI: 10.1002/ajmg.c.32056 -
Journal of Medical Genetics Nov 2022A neurodevelopmental syndrome was recently reported in four patients with heterozygous missense variants in the high-mobility-group (HMG) DNA-binding domain. The...
BACKGROUND
A neurodevelopmental syndrome was recently reported in four patients with heterozygous missense variants in the high-mobility-group (HMG) DNA-binding domain. The present study aimed to consolidate clinical and genetic knowledge of this syndrome.
METHODS
We newly identified 17 patients with variants, predicted variant pathogenicity using in silico tests and in vitro functional assays and analysed the patients' phenotypes.
RESULTS
All variants were novel, distinct and heterozygous. Seven HMG-domain missense and five stop-gain variants were classified as pathogenic or likely pathogenic variant (L/PV) as they precluded SOX4 transcriptional activity in vitro. Five HMG-domain and non-HMG-domain missense variants were classified as of uncertain significance (VUS) due to negative results from functional tests. When known, inheritance was de novo or from a mosaic unaffected or non-mosaic affected parent for patients with L/PV, and from a non-mosaic asymptomatic or affected parent for patients with VUS. All patients had neurodevelopmental, neurological and dysmorphic features, and at least one cardiovascular, ophthalmological, musculoskeletal or other somatic anomaly. Patients with L/PV were overall more affected than patients with VUS. They resembled patients with other neurodevelopmental diseases, including the related and Coffin-Siris (CSS) syndromes, but lacked the most specific features of CSS.
CONCLUSION
These findings consolidate evidence of a fairly non-specific neurodevelopmental syndrome due to haploinsufficiency in neurogenesis and multiple other developmental processes.
Topics: Humans; Micrognathism; Hand Deformities, Congenital; Intellectual Disability; Neurodevelopmental Disorders; Syndrome; Phenotype; DNA; SOXC Transcription Factors
PubMed: 35232796
DOI: 10.1136/jmedgenet-2021-108375