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Stem Cell Reports Dec 2023Disruption of global ribosome biogenesis selectively affects craniofacial tissues with unclear mechanisms. Craniosynostosis is a congenital craniofacial disorder...
Disruption of global ribosome biogenesis selectively affects craniofacial tissues with unclear mechanisms. Craniosynostosis is a congenital craniofacial disorder characterized by premature fusion of cranial suture(s) with loss of suture mesenchymal stem cells (MSCs). Here we focused on ribosomopathy disease gene Snord118, which encodes a small nucleolar RNA (snoRNA), to genetically disturb ribosome biogenesis in suture MSCs using mouse and human induced pluripotent stem cell (iPSC) models. Snord118 depletion exhibited p53 activation, increased cell death, reduced proliferation, and premature osteogenic differentiation of MSCs, leading to suture growth and craniosynostosis defects. Mechanistically, Snord118 deficiency causes translational dysregulation of ribosomal proteins and downregulation of complement pathway genes. Further complement pathway disruption by knockout of complement C3a receptor 1 (C3ar1) exacerbated MSC and suture defects in mutant mice, whereas activating the complement pathway rescued MSC cell fate and suture growth defects. Thus, ribosome biogenesis controls MSC fate via the complement pathway to prevent craniosynostosis.
Topics: Humans; Mice; Animals; Cranial Sutures; Osteogenesis; Induced Pluripotent Stem Cells; Craniosynostoses; Cell Differentiation; Ribosomes
PubMed: 37977145
DOI: 10.1016/j.stemcr.2023.10.015 -
Joint multi-ancestry and admixed GWAS reveals the complex genetics behind human cranial vault shape.Nature Communications Nov 2023The cranial vault in humans is highly variable, clinically relevant, and heritable, yet its genetic architecture remains poorly understood. Here, we conduct a joint... (Review)
Review
The cranial vault in humans is highly variable, clinically relevant, and heritable, yet its genetic architecture remains poorly understood. Here, we conduct a joint multi-ancestry and admixed multivariate genome-wide association study on 3D cranial vault shape extracted from magnetic resonance images of 6772 children from the ABCD study cohort yielding 30 genome-wide significant loci. Follow-up analyses indicate that these loci overlap with genomic risk loci for sagittal craniosynostosis, show elevated activity cranial neural crest cells, are enriched for processes related to skeletal development, and are shared with the face and brain. We present supporting evidence of regional localization for several of the identified genes based on expression patterns in the cranial vault bones of E15.5 mice. Overall, our study provides a comprehensive overview of the genetics underlying normal-range cranial vault shape and its relevance for understanding modern human craniofacial diversity and the etiology of congenital malformations.
Topics: Child; Humans; Animals; Mice; Genome-Wide Association Study; Skull; Craniosynostoses; Facial Bones; Brain
PubMed: 37973980
DOI: 10.1038/s41467-023-43237-8 -
The Journal of Craniofacial SurgeryHydrocephalus is variously associated with syndromic craniosynostosis (CS), while it is randomly encountered in nonsyndromic CS. But actually, the ventriculomegaly in CS...
Hydrocephalus is variously associated with syndromic craniosynostosis (CS), while it is randomly encountered in nonsyndromic CS. But actually, the ventriculomegaly in CS is less described. In this study, the authors aim to establish whether ventriculomegaly is common in patients with CS, in both syndromic and nonsyndromic. Retrospective measurements of Evans index (EI) were taken from thin-section computed tomography scans of 169 preoperative CS patients to assess cerebral ventricular volume. EI >0.3 indicates ventricular enlargement. A total of 169 CS patients who underwent computed tomography scan from February 2018 to December 2021 were retrospectively evaluated, including 114 males and 55 females. The average age at diagnosis was 16 months (range: 1-103 mo). Among them, 37 with syndromic CS, including 17 ventricular megaly patients, had an EI >0.3 (46.0%), and 4 of them had intracranial hypertension and needed ventriculoperitoneal shunt treatment before cranial vault remolding. One hundred and thirty-two had nonsyndromic CS (100 single-suture CS, 32 multisuture CS), and 26 of them had an EI of 0.3 or greater (19.7%). Ventrocular megaly is common among patients with CS. Early craniotomy may stabilize ventricular dilation.
Topics: Male; Female; Humans; Infant; Child, Preschool; Child; Retrospective Studies; Incidence; Craniosynostoses; Skull; Hydrocephalus
PubMed: 37955451
DOI: 10.1097/SCS.0000000000009805 -
The Journal of Foot and Ankle Surgery :... 2024Little is known about functional outcomes in children with treated lower extremity polydactyly (LEP). No classification system has been shown to be prognostically useful...
Little is known about functional outcomes in children with treated lower extremity polydactyly (LEP). No classification system has been shown to be prognostically useful for functional outcomes. This study investigates whether children with treated LEP learn to walk at an age comparable to the population and whether the SAM (severity of syndactyly, axis deviation and metatarsal involvement) classification system is prognostically useful. In a retrospective cohort of 18 patients, we tested for associations between patient characteristics and SAM scores, age at learning to walk, and ability to fit off-the-shelf shoes. The proportion of children with treated LEP able to walk at 18 months of age was compared with the general population. We found no association between the age at which the 17 participants learned to walk and the severity of syndactyly (p = .214), axis deviation (p = .723) and metatarsal involvement (p = .781), nor between the proportion of patients able to wear off-the-shelf shoes compared to those requiring extra wide off-the-shelf shoes and the severity of syndactyly (p = 1.000), axis deviation (p = 1.000) and metatarsal involvement (p = 1.000). We found a trend between older age at surgery and the need for extra wide off-the-shelf shoes (OR = 1.008, p = .080). We found no significant difference in the proportion of children able to walk at 18 months between our patients (proportion = 1.00) and the general population (proportion = 0.95) (p = 1.000). We found no significant association between different SAM scores and functional outcomes, and none in the proportion of children able to walk at 18 months between treated LEP patients and the general population.
Topics: Child; Humans; Toes; Retrospective Studies; Foot; Polydactyly; Syndactyly
PubMed: 37951458
DOI: 10.1053/j.jfas.2023.11.004 -
American Journal of Speech-language... Jan 2024Craniofacial microsomia (CFM) is a complex congenital condition primarily affecting the ear, mandible, facial nerve and muscles, and tongue. Individuals with CFM are at... (Review)
Review
INTRODUCTION
Craniofacial microsomia (CFM) is a complex congenital condition primarily affecting the ear, mandible, facial nerve and muscles, and tongue. Individuals with CFM are at increased risk of hearing loss, obstructive sleep apnea, and feeding/swallowing difficulties. The purpose of this scoping review was to summarize evidence pertaining to speech production in CFM.
METHOD
All articles reporting any characteristic of speech production in CFM were included and screened by two independent reviewers by title, abstract, and full text. Data charting captured details related to study population and design, CFM diagnostic criteria, speech outcome measurement, and key findings. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews checklist guided reporting of results. Our protocol was registered on the Open Science Framework (https://osf.io/npr94/) and published elsewhere.
RESULTS
Forty-five articles were included in the detailed review. Most articles originated from the United States, were published in the past decade, and utilized case report/series study design. A speech-language pathologist authored 29%. The prevalence of velopharyngeal insufficiency ranged from 19% to 55% among studies. Oral distortion of alveolar and palatal fricatives and affricates primarily characterized articulation errors. Studies identified increased disordered speech and lower intelligibility in adolescents with CFM compared to unaffected peers. Evidence pertaining to phonatory and respiratory speech findings is limited.
CONCLUSIONS
Evidence supports that individuals with CFM are at increased risk of both velopharyngeal and articulatory speech differences. Additional information is needed to develop speech screening guidelines for children with CFM. Heterogeneity in study design and outcome measurement precludes comparisons across studies.
SUPPLEMENTAL MATERIAL
https://doi.org/10.23641/asha.24424555.
Topics: Child; Adolescent; Humans; United States; Goldenhar Syndrome; Speech; Speech Disorders; Communication Disorders; Phenotype
PubMed: 37931079
DOI: 10.1044/2023_AJSLP-23-00152 -
The Journal of Clinical Investigation Nov 2023Skull development coincides with the onset of cerebrospinal fluid (CSF) circulation, brain-CSF perfusion, and meningeal lymphangiogenesis, processes essential for brain...
Skull development coincides with the onset of cerebrospinal fluid (CSF) circulation, brain-CSF perfusion, and meningeal lymphangiogenesis, processes essential for brain waste clearance. How these processes are affected by craniofacial disorders such as craniosynostosis are poorly understood. We report that raised intracranial pressure and diminished CSF flow in craniosynostosis mouse models associate with pathological changes to meningeal lymphatic vessels that affect their sprouting, expansion, and long-term maintenance. We also show that craniosynostosis affects CSF circulatory pathways and perfusion into the brain. Further, craniosynostosis exacerbates amyloid pathology and plaque buildup in Twist1+/-:5xFAD transgenic Alzheimer's disease models. Treating craniosynostosis mice with Yoda1, a small molecule agonist for Piezo1, reduces intracranial pressure and improves CSF flow, in addition to restoring meningeal lymphangiogenesis, drainage to the deep cervical lymph nodes, and brain-CSF perfusion. Leveraging these findings, we show that Yoda1 treatments in aged mice with reduced CSF flow and turnover improve lymphatic networks, drainage, and brain-CSF perfusion. Our results suggest that CSF provides mechanical force to facilitate meningeal lymphatic growth and maintenance. Additionally, applying Yoda1 agonist in conditions with raised intracranial pressure and/or diminished CSF flow, as seen in craniosynostosis or with ageing, is a possible therapeutic option to help restore meningeal lymphatic networks and brain-CSF perfusion.
Topics: Mice; Animals; Glymphatic System; Brain; Lymphatic Vessels; Perfusion; Craniosynostoses; Drainage; Ion Channels
PubMed: 37917195
DOI: 10.1172/JCI171468 -
Child's Nervous System : ChNS :... Mar 2024To evaluate the long-term anthropometric measurements, cosmetic satisfaction, and other patient-reported outcome measures (PROMs) of patients who underwent surgical...
PURPOSE
To evaluate the long-term anthropometric measurements, cosmetic satisfaction, and other patient-reported outcome measures (PROMs) of patients who underwent surgical treatment or observation only of sagittal or metopic single-suture craniosynostosis (SSC).
METHODS
A prospective study was designed for all patients diagnosed with non-syndromic sagittal and metopic craniosynostosis at the British Columbia Children's Hospital, Vancouver, Canada, in the period July 1986 to July 2006. After a minimum of 15 years post-diagnosis, all eligible patients were invited to fill out the Craniofacial Surgery Outcomes Questionnaire (CSO-Q) and to attend a scheduled follow-up appointment for the collection of anthropometric measurements. A descriptive analysis of the cosmetic results was performed. Statistical analyses compared the differences in anthropometric measurements between treated and non-treated patients.
RESULTS
Of the 253 eligible patients, 52 participants were willing to share patient data for use in the study. Of those 52 former patients, 36 (69.2%) filled out and returned the CSO-Q and 23 (44.2%) attended the follow-up appointment. The mean follow-up period between surgical treatment and the CSO-Q was 20.2 ± 2.5 years and between surgical treatment and the follow-up appointment was 20.9 ± 2.7 years. In patients with sagittal SSC, the mean cephalic index (CI) was significantly larger in treated than in non-treated patients (74.6 versus 69.1, p = 0.04), while the mean pupillary distance and forehead to back index were significantly smaller (pupillary distance 6.0 cm versus 6.7 cm [p = 0.04] and forehead to back index 19.6 cm versus 21.1 cm [p = 0.03]). Focusing more on the patient reported outcome measures, overall cosmetic satisfaction was found to be high (80.6%) and no differences were found between sagittal and metopic synostosis patients, nor between treated or non-treated craniosynostosis patients. Overall outcomes regarding self-esteem (RSES) and fear of negative evaluation (FNE) were comparable with population based outcomes.
CONCLUSION
This is the first prospective study of sagittal and metopic craniosynostosis patients regarding long-term anthropometric outcome and patient reported outcome measures, including patients who were treated surgically and those who received observation only. Although study participation two decades after initial diagnosis was difficult to obtain, our data provide a platform from which one can develop an inclusive and uniform approach to assess patients' subjective cosmetic satisfaction using the CSO-Questionnaire and might be useful in preoperative counseling and psychosocial care for patients and their families.
Topics: Child; Humans; Infant; Prospective Studies; Craniosynostoses; British Columbia; Treatment Outcome; Retrospective Studies
PubMed: 37914832
DOI: 10.1007/s00381-023-06202-w -
Andes Pediatrica : Revista Chilena de... Jan 2023To describe the presence of obstructive sleep apnea syndrome (OSAS) in children with craniofacial anomalies (CFA), associate biodemographic characteristics and polygraph...
OBJECTIVE
To describe the presence of obstructive sleep apnea syndrome (OSAS) in children with craniofacial anomalies (CFA), associate biodemographic characteristics and polygraph variables, and analyze the therapeutic management decided after the sleep study and the evaluation by a multidisciplinary team.
PATIENTS AND METHOD
Retrospective study. Polygraphs were performed on patients aged between 1 month and 19 years with CFA. An initial and projected management was established categorized into ventilatory support, tracheostomy, surgery, dental, and medical treatment. Descrip tive and inferential statistics were performed, evaluating the association between demographic and polygraph variables and therapeutic management.
RESULTS
34 patients were included with a median age of 4.0 years (IQR 0.9 - 6.5). Diagnosis was 41.2% cleft lip and palate, 35.3% craniosynostosis, and 23.5% micrognathia. Polygraphs were altered in 70.6% of the cases; of these, 26.5% were diagnosed as mild, 5.9% moderate, and 38.2% severe OSAS. There was an association between minimum satu ration and diagnosis of OSAS (p = 0.0036), and in the presence of OSAS with the initial management applied (p=0.0013). There was no significant relationship between the different types of CFA with the initial therapeutic management (p = 0.6565). Initial and projected managements, respectively: Venti latory support (11.8% and 2.9%), tracheostomy (11.8% and 0%), surgery (35.2% and 26.5%), dental (20.6% and 53%), and medical treatment (20.6% and 17.6 %).
CONCLUSIONS
70% of the patients with CFA presented OSAS. The greatest severity was found in Cleft Lip and Palatine and Craniosynostosis. Therapeutic management was mainly oriented towards initial surgical and planned dental treatments based on the diagnosis of OSAS and not on the type of CFA.
Topics: Humans; Child; Adolescent; Infant; Child, Preschool; Cleft Lip; Retrospective Studies; Cleft Palate; Sleep Apnea, Obstructive; Craniosynostoses; Sleep
PubMed: 37906869
DOI: 10.32641/andespediatr.v94i1.4179 -
Journal of Feline Medicine and Surgery Oct 2023The aim of this study was to determine whether an association existed between cephalometric measurements, maxillomandibular dental arch distances and the occurrence of...
OBJECTIVES
The aim of this study was to determine whether an association existed between cephalometric measurements, maxillomandibular dental arch distances and the occurrence of traumatic malocclusions in the mandibular soft tissues of cats.
METHODS
Cats that had presented for dental consultations and that underwent cone-beam CT during diagnostic assessment were included in the study and categorised as cases and controls in a 1:2 ratio. Cases were designated as cats with a clinical diagnosis of malocclusion causing trauma to the buccal mandibular soft tissues or pyogenic granuloma secondary to the trauma, and controls were designated as cats with the absence of such diagnoses and without a history of other musculoskeletal anomalies in the head. Cephalometric measurements, including skull and facial indexes, as well as distances and angulations between dental crowns and crown tips, were calculated and analysed statistically.
RESULTS
In total, 72 cats (24 cases and 48 controls) were included in the study. Cephalometric measurements revealed a significant association between the skull and facial indexes and the occurrence of traumatic malocclusions in the caudal teeth. Brachycephaly was a strong predictor of the occurrence of traumatic malocclusions. In addition, the space between crown tips and teeth angulations was a contributing factor to the trauma.
CONCLUSIONS AND RELEVANCE
Cats with traumatic malocclusions in the cheek teeth tend to present a narrower interdental space between the maxillary and mandibular carnassial teeth, mostly attributed to skeletal and dental malocclusion. These findings can be used to help raise awareness about this disease in cats and its association with brachycephaly. Cut-off values have been proposed and could be used in the selection of cats by breeders to reduce the occurrence of this disease.
Topics: Cats; Animals; Retrospective Studies; Case-Control Studies; Mandible; Malocclusion; Craniosynostoses; Cat Diseases
PubMed: 37906203
DOI: 10.1177/1098612X231202322 -
Veterinary Medicine and Science Nov 2023Brachycephalic obstructive airway syndrome (BOAS) comprises a group of anatomical upper respiratory tract abnormalities that collectively result in various degrees of...
Brachycephalic obstructive airway syndrome (BOAS) comprises a group of anatomical upper respiratory tract abnormalities that collectively result in various degrees of upper respiratory tract obstruction. Stenotic nares is a common feature of BOAS, and in dogs, the main cause is axial deviation of the alar cartilage. In contrast, narrowing of the nares in cats is predominantly the result of a redundant skin fold at the junction of the ventral floor of the nostrils and the haired skin of the lip. Three brachycephalic cats with inspiratory obstruction were referred to the surgery department of the Veterinary Teaching Hospital of Ferdowsi University of Mashhad, Iran. The predominant cause of obstruction was nostril stenosis due to the presence of redundant skin on the ventral floor of the nares. All three cats underwent surgical correction using a single pedicle advancement flap technique, which was first described by Berns et al. (2020). All three cats had positive outcomes, with no surgical complications and no episodes of respiratory distress reported within a 9-month follow-up. Appropriate surgical treatment of feline patients with stenotic nares can result in good long-term outcomes.
Topics: Humans; Cats; Animals; Dogs; Constriction, Pathologic; Hospitals, Animal; Dog Diseases; Hospitals, Teaching; Nasal Cavity; Airway Obstruction; Craniosynostoses; Cat Diseases
PubMed: 37897212
DOI: 10.1002/vms3.1309