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European Journal of Medical Genetics Jun 2021This article reviews the development of research in the field of craniosynostosis from a bibliometric standpoint. Craniosynostosis is a malformation occurring during the... (Review)
Review
This article reviews the development of research in the field of craniosynostosis from a bibliometric standpoint. Craniosynostosis is a malformation occurring during the early development of the skull, when one or more of the sutures close too early, causing problems with normal brain and skull growth. Research in this field has developed from early clinical case descriptions, to genetic discoveries responsible for the occurring malformations and onwards to developing sophisticated surgical treatment. In this article we describe these developments, zoom in on publication trends and characteristics and visualize developing networks and topic shifts in this research field.
Topics: Bibliometrics; Biomedical Research; Craniosynostoses; Genetics, Medical; Humans; Periodicals as Topic
PubMed: 33866005
DOI: 10.1016/j.ejmg.2021.104224 -
The International Journal of... 2020Clinical dysmorphology is a medical specialty which requires training to systematically observe aberrations in facial development and to understand patterns in the... (Review)
Review
Clinical dysmorphology is a medical specialty which requires training to systematically observe aberrations in facial development and to understand patterns in the recognition of underlying genetic syndromes. An understanding of normal facial embryology and structure, genetic mechanisms that contribute to facial development and the influence of age, sex, epigenetic, environmental and teratogen effects that contribute to facial dysmorphology are essential. The role of software programmes and databases in achieving diagnoses in subtler phenotypes is growing. A description of specific dysmorphisms of various parts of the human face and key genetic and mechanistic pathways are discussed in this review. Recognizing facial patterns and genetic syndromes efficiently aids in planning appropriate tests, securing an accurate diagnosis, counselling and predicting outcomes and offering interventions and therapies where available.
Topics: Congenital Abnormalities; Craniosynostoses; Embryonic Development; Face; Female; Gene Expression Regulation, Developmental; Humans; Male; Mesoderm; Neural Crest
PubMed: 32658997
DOI: 10.1387/ijdb.190312mb -
Child's Nervous System : ChNS :... Nov 2022The foramen magnum (FM) presents various alterations in craniosynostoses, such as brachycephaly or Crouzon syndrome. However, to date, no study has been devoted to its...
PURPOSE
The foramen magnum (FM) presents various alterations in craniosynostoses, such as brachycephaly or Crouzon syndrome. However, to date, no study has been devoted to its morphology and morphometry in scaphocephaly, which is the most common of cranial deformities resulting from premature fusion of cranial sutures.
METHODS
We assessed the morphology and morphometry of FM using preoperative thin-cut CT scans of 107 children with non-syndromic sagittal craniosynostosis aged 1-12 months (mean age 5.38 months). A series of sagittal and transverse dimensions were taken and the FM area was calculated in each case. Obtained data were compared to the age-matched control group of 101 normocephalic children.
RESULTS
Dolichotrematous type of FM was dominant in the scaphocephaly group and observed in 63/107 cases (58.9%). The mean FM area in the scaphocephaly group was 519.64 mm and was significantly smaller compared to the control group (p = 0.0011). The transverse diameter and anterior sagittal diameter were also significantly smaller (p = 0.0112 and p = 0.0003, respectively).
CONCLUSION
The area of FM in scaphocephaly is smaller compared to normal individuals. This is associated with a significant reduction of the width of FM in children with sagittal craniosynostosis. FM in scaphocephaly is larger than in other reported series of children with brachycephaly or Crouzon syndrome.
Topics: Child; Humans; Infant; Foramen Magnum; Craniosynostoses; Craniofacial Dysostosis; Cranial Sutures; Tomography, X-Ray Computed; Skull
PubMed: 35931858
DOI: 10.1007/s00381-022-05624-2 -
BMJ Case Reports Aug 2019
Topics: Adult; Copper; Cough; Craniosynostoses; Humans; Incidental Findings; Male; Radiography; Skull; Tomography Scanners, X-Ray Computed; Young Adult
PubMed: 31466955
DOI: 10.1136/bcr-2019-230916 -
Orthodontics & Craniofacial Research Jun 2017It is suggested that craniosynostosis is caused by a heterogeneous set of effects including gene mutations, teratogenic exposure during critical periods of development... (Review)
Review
It is suggested that craniosynostosis is caused by a heterogeneous set of effects including gene mutations, teratogenic exposure during critical periods of development and gene/environment interactions. Distinguishing between sufficient, additive and interactive effects is important to the study of gene/environment interactions and allows for segregation of environmental exposures effecting susceptible populations. Through the identification of sufficient and interactive effects, efforts in prevention of craniosynostosis may be successful. Here, we provide a brief review focusing on defining these categorized exposures and relevant literature that has interrogated gene/environment interactions for craniosynostosis.
Topics: Craniosynostoses; Gene-Environment Interaction; Humans; Mutation; Phenotype
PubMed: 28643932
DOI: 10.1111/ocr.12153 -
Brain Structure & Function Dec 2023The shape of the cranium is one of the most notable physical changes induced in domestic dogs through selective breeding and is measured using the cephalic index (CI)....
The shape of the cranium is one of the most notable physical changes induced in domestic dogs through selective breeding and is measured using the cephalic index (CI). High CI (a ratio of skull width to skull length > 60) is characterized by a short muzzle and flat face and is referred to as brachycephaly. Brachycephalic dogs display some potentially harmful changes in neuroanatomy, and there are implications for differences in behavior, as well. The path from anatomy to cognition, however, has not been charted in its entirety. Here, we report that sleep-physiological markers of white-matter loss (high delta power, low frontal spindle frequency, i.e., spindle waves/s), along with a spectral profile for REM (low beta, high delta) associated with low intelligence in humans, are each linked to higher CI values in the dog. Additionally, brachycephalic subjects spent more time sleeping, suggesting that the sleep apnea these breeds usually suffer from increases daytime sleepiness. Within sleep, more time was spent in the REM sleep stage than in non-REM, while REM duration was correlated positively with the number of REM episodes across dogs. It is currently not clear if the patterns of sleep and sleep-stage duration are mainly caused by sleep-impairing troubles in breathing and thermoregulation, present a juvenile-like sleeping profile, or are caused by neuro-psychological conditions secondary to the effects of brachycephaly, e.g., frequent REM episodes are known to appear in human patients with depression. While future studies should more directly address the interplay of anatomy, physiology, and behavior within a single experiment, this represents the first description of how the dynamics of the canine brain covary with CI, as measured in resting companion dogs using a non-invasive sleep EEG methodology. The observations suggest that the neuroanatomical changes accompanying brachycephaly alter neural systems in a way that can be captured in the sleep EEG, thus supporting the utility of the latter in the study of canine brain health and function.
Topics: Dogs; Humans; Animals; Sleep; Sleep, REM; Electroencephalography; Brain; Craniosynostoses
PubMed: 37742302
DOI: 10.1007/s00429-023-02706-y -
Ultrasound in Obstetrics & Gynecology :... Feb 1997
Topics: Congenital Abnormalities; Craniosynostoses; Humans; Ultrasonography
PubMed: 9132258
DOI: 10.1046/j.1469-0705.1997.09020073.x -
PloS One 2021For many years, there has been a trend to breed cats with an increasing degree of brachycephalic head features, which are known to have a severe impact on the animals'...
For many years, there has been a trend to breed cats with an increasing degree of brachycephalic head features, which are known to have a severe impact on the animals' health and welfare. The direct relation between different grades of brachycephaly and their negative implications have not been researched in this species. The aim of this study was therefore to establish correlations between the different grades of brachycephaly and reduced upper respiratory airways, exophthalmos of the eye globes and malalignment of the teeth in Persian cats. Sixty-nine Persian cats of various skull dimensions and ten Domestic shorthair cats were recruited for the study. The cats' skulls were examined using three-dimensional reconstructions created from Computed Tomography datasets. Brachycephaly was graded using established craniometric measurements (facial index, cranial index, skull index, craniofacial angle). The flow area of the nasal passageways at different locations, the amount of the eye globe not supported by the bony orbit and the axial deviation of the teeth were quantified and evaluated for a correlation with the grade of brachycephaly. The results of this study clearly show that increased grades of brachycephaly in Persian cats resulted in larger extra-orbital parts of the ocular bulbs. The brachycephalic skull dimension also resulted in a lower height of the naso-osseal aperture, while other areas of the nasal airways were not correlated with the severity of brachycephaly. Persian cats showed a significantly increased occurrence of premolar tooth displacement in the upper jaw with increasing brachycephaly grades. It was interesting to note that the measured values had a broad range and values of some individual Persian cats showed an overlap with those of Domestic shorthair cats.
Topics: Animals; Cats; Craniosynostoses; Exophthalmos; Nasal Cavity; Skull; Tomography, X-Ray Computed; Tooth Abnormalities
PubMed: 34288937
DOI: 10.1371/journal.pone.0254420 -
International Journal of Molecular... Apr 2023ETS2 repressor factor () insufficiency causes craniosynostosis (CRS4) in humans and mice. ERF is an ETS domain transcriptional repressor regulated by Erk1/2...
ETS2 repressor factor () insufficiency causes craniosynostosis (CRS4) in humans and mice. ERF is an ETS domain transcriptional repressor regulated by Erk1/2 phosphorylation via nucleo-cytoplasmic shuttling. Here, we analyze the onset and development of the craniosynostosis phenotype in an Erf-insufficient mouse model and evaluate the potential of the residual Erf activity augmented by pharmacological compounds to ameliorate the disease. Erf insufficiency appears to cause an initially compromised frontal bone formation and subsequent multisuture synostosis, reflecting distinct roles of Erf on the cells that give rise to skull and facial bones. We treated animals with Mek1/2 and nuclear export inhibitors, U0126 and KPT-330, respectively, to increase Erf activity by two independent pathways. We implemented both a low dosage locally over the calvaria and a systemic drug administration scheme to evaluate the possible indirect effects from other systems and minimize toxicity. The treatment of mice with either the inhibitors or the administration scheme alleviated the synostosis phenotype with minimal adverse effects. Our data suggest that the ERF level is an important regulator of cranial bone development and that pharmacological modulation of its activity may represent a valid intervention approach both in CRS4 and in other syndromic forms of craniosynostosis mediated by the FGFR-RAS-ERK-ERF pathway.
Topics: Animals; Mice; Craniosynostoses; MAP Kinase Signaling System; Phosphorylation; Repressor Proteins; Skull; Transcription Factors
PubMed: 37175668
DOI: 10.3390/ijms24097961 -
Journal of Integrative Neuroscience Jun 2022Craniosynostosis is a rare congenital disease of the skull. They arise when one or more cranial sutures ossify prematurely. This causes an obstruction to normal brain...
BACKGROUND
Craniosynostosis is a rare congenital disease of the skull. They arise when one or more cranial sutures ossify prematurely. This causes an obstruction to normal brain growth and leads to specific deformations of the skull, which may result in intracranial hypertension and cognitive delay.
MATERIALS AND METHODS
We have retrospectively analysed all children treated at the Unit of paediatric neurosurgery of the University Medical Centre Ljubljana between June 2015 and September 2020. The following items have been recorded: affected suture, underlying syndromic condition, hydrocephalus, Chiari malformation, raised intracranial pressure, age at surgery, surgical technique, need for multiple operations and surgical complications.
RESULTS
During the study period, 71 children have been treated for craniosynostosis. The median postoperative follow-up was 31 months. There were: 54.9% sagittal, 25.3% metopic, 14.0% unicoronal, 1.4% bicoronal and 1.4% unilateral lambdoid craniosynostosis. Multiple sutures were affected in 2.8% cases. 7.0% of the cases were syndromic. Overall, 74 surgical procedures have been performed: frontoorbital advancement represented 40.5% of them; biparietal remodelling 32.4%: total cranial vault remodelling 22.9%; posterior distraction 2.7%; posterior expansion 1.3%. Median age at surgery was 12.8 months.
CONCLUSIONS
The treatment of craniosynostosis is surgical and requires a multidisciplinary approach, with expertise in plastic and reconstructive surgery, maxillofacial surgery and neurosurgery. The aim of surgical treatment is to release the constrictive and deformative effect that the synostosis has on skull growth. This requires a remodelling of the neurocranium and, if necessary, of the viscerocranium. Beyond aesthetic purposes, the primary aim of surgical treatment is to permit a normal development of the brain.
Topics: Child; Cranial Sutures; Craniosynostoses; Humans; Plastic Surgery Procedures; Retrospective Studies; Skull
PubMed: 35864758
DOI: 10.31083/j.jin2104106