-
Clinical Oral Investigations Mar 2022To determine whether the midface of patients with Muenke syndrome, Saethre-Chotzen syndrome, or TCF12-related craniosynostosis is hypoplastic compared to skeletal facial...
OBJECTIVES
To determine whether the midface of patients with Muenke syndrome, Saethre-Chotzen syndrome, or TCF12-related craniosynostosis is hypoplastic compared to skeletal facial proportions of a Dutch control group.
MATERIAL AND METHODS
We included seventy-four patients (43 patients with Muenke syndrome, 22 patients with Saethre-Chotzen syndrome, and 9 patients with TCF12-related craniosynostosis) who were referred between 1990 and 2020 (age range 4.84 to 16.83 years) and were treated at the Department of Oral Maxillofacial Surgery, Special Dental Care and Orthodontics, Children's Hospital Erasmus University Medical Center, Sophia, Rotterdam, the Netherlands. The control group consisted of 208 healthy children.
RESULTS
Cephalometric values comprising the midface were decreased in Muenke syndrome (ANB: β = -1.87, p = 0.001; and PC1: p < 0,001), Saethre-Chotzen syndrome (ANB: β = -1.76, p = 0.001; and PC1: p < 0.001), and TCF12-related craniosynostosis (ANB: β = -1.70, p = 0.015; and PC1: p < 0.033).
CONCLUSIONS
In this study, we showed that the midface is hypoplastic in Muenke syndrome, Saethre-Chotzen syndrome, and TCF12-related craniosynostosis compared to the Dutch control group. Furthermore, the rotation of the maxilla and the typical craniofacial buildup is significantly different in these three craniosynostosis syndromes compared to the controls.
CLINICAL RELEVANCE
The maxillary growth in patients with Muenke syndrome, Saethre-Chotzen syndrome, or TCF12-related craniosynostosis is impaired, leading to a deviant dental development. Therefore, timely orthodontic follow-up is recommended. In order to increase expertise and support treatment planning by medical and dental specialists for these patients, and also because of the specific differences between the syndromes, we recommend the management of patients with Muenke syndrome, Saethre-Chotzen syndrome, or TCF12-related craniosynostosis in specialized multidisciplinary teams.
Topics: Acrocephalosyndactylia; Adolescent; Basic Helix-Loop-Helix Transcription Factors; Cephalometry; Child; Child, Preschool; Craniosynostoses; Humans; Syndrome
PubMed: 34904178
DOI: 10.1007/s00784-021-04275-y -
Neurosurgery Clinics of North America Jan 2022Craniosynostosis involves the premature fusion of 1 or more cranial sutures and commonly presents as an isolated, nonsyndromic diagnosis. A subset of patients have... (Review)
Review
Craniosynostosis involves the premature fusion of 1 or more cranial sutures and commonly presents as an isolated, nonsyndromic diagnosis. A subset of patients have syndromic craniosynostosis. Several unique considerations must be taken into account when managing patients with syndromic craniosynostosis. A multidisciplinary craniofacial team with a central coordinator is particularly useful for coordinating care among various specialists, and close monitoring is mandatory owing to the increased risk of intracranial hypertension. Surgical management varies among centers, but core options include fronto-orbital advancement with cranial vault remodeling, posterior vault expansion, endoscopic-assisted suturectomy with postoperative orthotic therapy, and midface advancement.
Topics: Craniosynostoses; Humans; Infant; Intracranial Hypertension; Skull; Syndrome
PubMed: 34801135
DOI: 10.1016/j.nec.2021.09.008 -
The Cleft Palate-craniofacial Journal :... Jun 2022Pfeiffer syndrome is one of the autosomal dominant craniofacial syndromes. Classical clinical manifestations are coronal suture synostosis causing brachycephaly, midface...
Pfeiffer syndrome is one of the autosomal dominant craniofacial syndromes. Classical clinical manifestations are coronal suture synostosis causing brachycephaly, midface retrusion, airway compromise, broad thumbs, and toes. Pfeiffer syndrome type I (classic type) is associated with mutation. However, wide range of clinical manifestations, with and without craniosynostosis, have been reported. Here, we present a family of Pfeiffer syndrome across 3 generations with identical : c.755C>G (p.Pro252Arg) mutation. Where the members of the youngest generation have no cranial involvement. Lastly, we propose a guideline management for familial Pfeiffer syndrome management.
Topics: Acrocephalosyndactylia; Craniosynostoses; Humans; Mutation; Patient Care Team; Skull
PubMed: 34238036
DOI: 10.1177/10556656211028505 -
In Vivo (Athens, Greece) 2023Craniosynostosis refers to the early fusion of one or many cranial sutures, causing craniofacial abnormalities observed in 1:2,500 births worldwide. In most cases (85%),... (Review)
Review
Craniosynostosis refers to the early fusion of one or many cranial sutures, causing craniofacial abnormalities observed in 1:2,500 births worldwide. In most cases (85%), craniosynostosis is presented as sporadic anomaly (non-syndromic craniosynostosis), while in other cases (15%) as part of syndromes (syndromic craniosynostosis). Patients with syndromic disorder usually have more severe symptoms compared to those with single suture synostosis. Most common syndromes of craniosynostosis include Pfeiffer, Apert, Crouzon, Jackson-Weiss, Muenke and Boston type MSX2-related syndrome. The main gene mutations in craniosynostosis involve FGFR1, FGFR2, FGFR3, TWIST1 and MSX2, which encode key factors influencing cranial bone morphogenesis. The main therapeutic approaches are surgical as discussed in this review, and the type of therapy depends on the graveness of the incident.
Topics: Humans; Craniosynostoses; Skull; Mutation; Syndrome
PubMed: 36593018
DOI: 10.21873/invivo.13052 -
Child's Nervous System : ChNS :... Jun 2021The most commonly occurring syndromic craniosynostoses are Apert syndrome, Crouzon syndrome, Pfeiffer syndrome, and Saethre-Chotzen syndrome. There is insufficient data...
PURPOSE
The most commonly occurring syndromic craniosynostoses are Apert syndrome, Crouzon syndrome, Pfeiffer syndrome, and Saethre-Chotzen syndrome. There is insufficient data regarding postoperative syndrome-related outcomes following the posterior vault distraction osteogenesis (PVDO) procedure, as well as data addressing whether or not additional procedures will be subsequently necessary to comprehensively treat children who undergo PVDO. Thus, the objective of this study is to describe and compare syndrome-related potential complications and outcomes associated with the PVDO procedure.
METHODS
An observational retrospective study was performed on consecutive patients (n=24) with Apert syndrome, Crouzon syndrome, Pfeiffer syndrome, or Saethre-Chotzen syndrome, respectively, who underwent PVDO between 2012 and 2019. Demographic data (patient gender and age when the PVDO procedure was performed), diagnosis, surgery-related data, and outcome data (perioperative and midterm complications and need for additional surgery) were verified.
RESULTS
Total relative blood transfusion volumes per kilogram for the patients were as follows: 22.75 ± 9.30 ml for Apert syndrome, 10.73 ± 2.28 ml for Crouzon syndrome (Apert versus Crouzon, p<0.05), 18.53 ± 8.08 ml for Pfeiffer syndrome, and 19.74 ± 9.12 ml for Saethre-Chotzen syndrome. None of the patients required a secondary procedure to alleviate intracranial pressure except for a Saethre-Chotzen patient.
CONCLUSION
PVDO is an effective technique to address elevated intracranial pressure in SC patients that alleviates the need for secondary procedures at midterm follow-up. Apert syndrome patients presented relatively higher total blood transfusion rates than Crouzon syndrome patients who were operated on at a later age and weighed more.
Topics: Acrocephalosyndactylia; Child; Craniofacial Dysostosis; Craniosynostoses; Humans; Osteogenesis, Distraction; Retrospective Studies
PubMed: 33866411
DOI: 10.1007/s00381-021-05169-w -
Frontiers in Genetics 2022The Crouzon syndrome mouse model carries a cysteine to tyrosine substitution at amino acid position 342 (Cys342Tyr; C342Y) in the fibroblast growth factor receptor 2...
The Crouzon syndrome mouse model carries a cysteine to tyrosine substitution at amino acid position 342 (Cys342Tyr; C342Y) in the fibroblast growth factor receptor 2 () gene equivalent to a mutation commonly associated with Crouzon and Pfeiffer syndromes in humans. The Fgfr2c C342Y mutation results in constitutive activation of the receptor and is associated with upregulation of osteogenic differentiation. Crouzon syndrome mice show premature closure of the coronal suture and other craniofacial anomalies including malocclusion of teeth, most likely due to abnormal craniofacial form. Malformation of the mandible can precipitate a plethora of complications including disrupting development of the upper jaw and palate, impediment of the airway, and alteration of occlusion necessary for proper mastication. The current paradigm of mandibular development assumes that Meckel's cartilage (MC) serves as a support or model for mandibular bone formation and as a template for the later forming mandible. If valid, this implies a functional relationship between MC and the forming mandible, so mandibular dysmorphogenesis might be discerned in MC affecting the relationship between MC and mandibular bone. Here we investigate the relationship of MC to mandible development from the early mineralization of the mandible (E13.5) through the initiation of MC degradation at E17.7 using Crouzon syndrome embryos and their unaffected littermates ( ). Differences between genotypes in both MC and mandibular bone are subtle, however MC of embryos is generally longer relative to unaffected littermates at E15.5 with specific aspects remaining relatively large at E17.5. In contrast, mandibular bone is smaller overall in embryos relative to their unaffected littermates at E15.5 with the posterior aspect remaining relatively small at E17.5. At a cellular level, differences are identified between genotypes early (E13.5) followed by reduced proliferation in MC (E15.5) and in the forming mandible (E17.5) in embryos. Activation of the ERK pathways is reduced in the perichondrium of MC in embryos and increased in bone related cells at E15.5. These data reveal that the Fgfr2c C342Y mutation differentially affects cells by type, location, and developmental age indicating a complex set of changes in the cells that make up the lower jaw.
PubMed: 35651944
DOI: 10.3389/fgene.2022.871927 -
Nature Biotechnology Nov 2023RNA base editing refers to the rewriting of genetic information within an intact RNA molecule and serves various functions, such as evasion of the endogenous immune... (Review)
Review
RNA base editing refers to the rewriting of genetic information within an intact RNA molecule and serves various functions, such as evasion of the endogenous immune system and regulation of protein function. To achieve this, certain enzymes have been discovered in human cells that catalyze the conversion of one nucleobase into another. This natural process could be exploited to manipulate and recode any base in a target transcript. In contrast to DNA base editing, analogous changes introduced in RNA are not permanent or inheritable but rather allow reversible and doseable effects that appeal to various therapeutic applications. The current practice of RNA base editing involves the deamination of adenosines and cytidines, which are converted to inosines and uridines, respectively. In this Review, we summarize current site-directed RNA base-editing strategies and highlight recent achievements to improve editing efficiency, precision, codon-targeting scope and in vivo delivery into disease-relevant tissues. Besides engineered editing effectors, we focus on strategies to harness endogenous adenosine deaminases acting on RNA (ADAR) enzymes and discuss limitations and future perspectives to apply the tools in basic research and as a therapeutic modality. We expect the field to realize the first RNA base-editing drug soon, likely on a well-defined genetic disease. However, the long-term challenge will be to carve out the sweet spot of the technology where its unique ability is exploited to modulate signaling cues, metabolism or other clinically relevant processes in a safe and doseable manner.
Topics: Humans; RNA; Gene Editing
PubMed: 37735261
DOI: 10.1038/s41587-023-01927-0 -
European Journal of Orthodontics May 2022To determine whether dental maturity (dental development) was delayed in patients with Muenke syndrome, Saethre-Chotzen syndrome, and TCF12-related craniosynostosis,...
OBJECTIVES
To determine whether dental maturity (dental development) was delayed in patients with Muenke syndrome, Saethre-Chotzen syndrome, and TCF12-related craniosynostosis, compared with a Dutch control group without syndromes.
MATERIALS AND METHODS
This study included 60 patients (38 patients with Muenke syndrome, 17 patients with Saethre-Chotzen syndrome, and 5 with TCF12-related craniosynostosis), aged 5.8-16.8 years that were treated at the Department of Oral Maxillofacial Surgery, Special Dental Care, and Orthodontics, in Sophia Children's Hospital, Erasmus University Medical Center, Rotterdam, the Netherlands. Dental age was calculated according to Demirjian's index of dental maturity. The control group included 451 children without a syndrome.
RESULTS
Compared with the control group, dental development was delayed by an average of one year in 5- to 8-year-old patients with Muenke syndrome (P = 0.007) and in 8- to 10-year-old patients with Saethre-Chotzen syndrome (P = 0.044), but not in patients with TCF12-related craniosynostosis.
CONCLUSIONS
Our results indicated that dental development was delayed by one year, on average, in patients with Muenke syndrome and Saethre-Chotzen syndrome, compared with a Dutch control group without syndromes.
IMPLICATIONS
Our findings have improved the understanding of dental development in patients with Muenke and Saethre-Chotzen syndrome. These results can provide guidance on whether the orthodontist needs to consider growth disturbances related to dental development.
Topics: Acrocephalosyndactylia; Basic Helix-Loop-Helix Transcription Factors; Child; Child, Preschool; Craniosynostoses; Humans; Netherlands; Syndrome
PubMed: 34424951
DOI: 10.1093/ejo/cjab056 -
Movement Disorders Clinical Practice May 2022There is a close link between multiple movement disorders and gastrointestinal dysfunction. Gastrointestinal symptoms may precede the development of the neurologic... (Review)
Review
There is a close link between multiple movement disorders and gastrointestinal dysfunction. Gastrointestinal symptoms may precede the development of the neurologic syndrome or may arise following the neurologic presentation. This review will provide an overview of gastrointestinal accompaniments to several well-known as well as lesser known movement disorders. It will also highlight several disorders which may not be considered primary movement disorders but have an overlapping presentation of both gastrointestinal and movement abnormalities.
PubMed: 35586541
DOI: 10.1002/mdc3.13407 -
Bone Reports Jun 2022Faciocraniosynostoses (FCS) are malformations affecting the development of the bones of the skull and face, due to the premature closure of one or more craniofacial...
OBJECTIVE
Faciocraniosynostoses (FCS) are malformations affecting the development of the bones of the skull and face, due to the premature closure of one or more craniofacial sutures, mostly secondary to activating () 1-3 mutations. Gain-of-function mutations are also responsible for various conditions referred to as osteochondrodysplasia (OCD), characterized by structural and functional abnormalities of growth plate cartilages. We hypothesized that patients with -related faciocraniosynostoses may present extra-cranial growth anomalies.
STUDY DESIGN
We retrospectively collected height and weight data from a cohort of 70 patients. Included patients were admitted for -related FCS between 2000 and 2021 at the Craniofacial Unit of Necker - Enfants Malades University Hospital in Paris, France.
RESULTS
We showed that -related faciocraniosynostoses had significantly reduced heights and weights relative to controls, and that two specific time periods (1-3 years and > 8 years of age) were associated with lower height and weight values. Four patients had received growth hormone treatment but remained below normal values for growth in height and weight.
CONCLUSIONS
Patients with -related faciocraniosynostoses have clinically significant extra-cranial anomalies which are not currently investigated and managed in usual protocols; these patients could benefit from a systematic pre-pubertal endocrine assessment. More generally, our results extend the scope of extracranial anomalies in -related faciocraniosynostoses and support the hypothesis that all conditions with activating mutations affect both membranous ossification and long bones.
PubMed: 35372644
DOI: 10.1016/j.bonr.2022.101524