Search results for "Craniosynostoses"
showing 10 items of 10 documents
Mutations in SKI in Shprintzen-Goldberg syndrome lead to attenuated TGF-β responses through SKI stabilization.
2020
ABSTRACTShprintzen-Goldberg syndrome (SGS) is a multisystemic connective tissue disorder, with considerable clinical overlap with Marfan and Loeys-Dietz syndromes. These syndromes have commonly been associated with enhanced TGF-β signaling. In SGS patients, heterozygous point mutations have been mapped to the transcriptional corepressor SKI, which is a negative regulator of TGF-β signaling that is rapidly degraded upon ligand stimulation. The molecular consequences of these mutations, however, are not understood. Here we use a combination of structural biology, genome editing and biochemistry to show that SGS mutations in SKI abolish its binding to phosphorylated SMAD2 and SMAD3. This resul…
Interstitial deletions of chromosome 1p: novel 1p31.3p22.2 microdeletion in a newborn with craniosynostosis, coloboma and cleft palate, and review of…
2022
Abstract Background Rearrangements of unstable DNA sequences may alter the structural integrity or the copy number of dose-sensitive genes, resulting in copy number variations. They may lead more frequently to deletions, in addition to duplications and/or inversions, which are the underlying pathogenic mechanism of a group of conditions known as genomic disorders (or also contiguous gene syndromes). Interstitial deletions of the short arm of chromosome 1 are rare, and only about 30 patients have been reported. Their clinical features are variable, in respect of the extent of the deleted region. They include global developmental delay, central nervous system (CNS) malformations, craniosynost…
Bone Fusion in Normal and Pathological Development is Constrained by the Network Architecture of the Human Skull
2016
The premature fusion of cranial bones, craniosynostosis, affects the correct development of the skull producing morphological malformations in newborns. To assess the susceptibility of each craniofacial articulation to close prematurely, we used a network model of the skull to quantify the link reliability (an index based on stochastic block modeling and Bayesian inference) of each articulation. We show that, of the 93 human skull articulations at birth, the few articulations that are associated with nonsyndromic craniosynostosis conditions have statistically significant lower reliability scores than the others. In a similar way, articulations that close during the normal postnatal developm…
Spring-Assisted Correction of Hypotelorism in Metopic Synostosis
2007
Metopic synostosis, apart from the pointed forehead, typically is characterized by hypotelorism with egg-shaped orbits on cephalography and the frontoorbital axis parallel or even converging superiorly. The frontoorbital axis angle is a novel parameter for analyzing and describing the orientation of the orbits. Current methods of surgery often result in undercorrection of the almost ever-present hypotelorism. The present study was performed to analyze a new technique, capable in this respect, using steel wire springs in conjunction with a cranioplasty.A retrospective study of 23 metopic synostosis patients operated on between 1999 and 2004 was conducted. A strip midline craniectomy and fron…
Delineation of a new chromosome 20q11.2 duplication syndrome including the ASXL1 gene.
2013
We report on three males with de novo overlapping 7.5, 9.8, and 10 Mb duplication of chromosome 20q11.2. Together with another patient previously published in the literature with overlapping 20q11 microduplication, we show that such patients display common clinical features including metopic ridging/trigonocephaly, developmental delay, epicanthal folds, and short hands. The duplication comprised the ASXL1 gene, in which de novo heterozygous nonsense or truncating mutations have recently been reported in patients with Borhing-Opitz syndrome. Because of craniofacial features in common with Borhing-Opitz syndrome, in particular metopic ridging/trigonocephaly, we suggest that duplication of ASX…
In-Frame Mutations in Exon 1 of SKI Cause Dominant Shprintzen-Goldberg Syndrome
2012
International audience; Shprintzen-Goldberg syndrome (SGS) is characterized by severe marfanoid habitus, intellectual disability, camptodactyly, typical facial dysmorphism, and craniosynostosis. Using family-based exome sequencing, we identified a dominantly inherited heterozygous in-frame deletion in exon 1 of SKI. Direct sequencing of SKI further identified one overlapping heterozygous in-frame deletion and ten heterozygous missense mutations affecting recurrent residues in 18 of the 19 individuals screened for SGS; these individuals included one family affected by somatic mosaicism. All mutations were located in a restricted area of exon 1, within the R-SMAD binding domain of SKI. No mut…
Phenotypic expression of the fibroblast growth factor receptor 3 (FGFR3) mutation P250R in a large craniosynostosis family.
1997
The craniosynostosis syndromes are a heterogeneous group of sporadic, autosomal dominant disorders with significant clinical overlap. Recently, we described a large family with autosomal dominant craniosynostosis suggestive of Saethre-Chotzen syndrome, in which linkage to the Saethre-Chotzen syndrome loci on 7p had been excluded. We now report the presence of a mutation in the fibroblast growth factor receptor 3 (FGFR3) in this family. The mutation, P250R, had been previously reported in 10 patients with non-syndromic craniosynostosis. Variable expression of this mutation is evident especially in two additional members of this family, one of whom is severely affected with pancraniosynostosi…
Subjective Assessment of Head and Facial Appearance in Children with Craniosynostoses after Surgical Treatment
2018
Background: Craniosynostoses are congenital defects in the construction of the skull involving premature fusion of one or more cranial sutures. Premature fusion of sutures causes characteristic skull deformation(s). This affect the structure and thus the appearance of the entire head and face. The aim of this study was to analyze parents&rsquo
Non-syndromic craniosynostosis in children : scoping review
2017
Background Craniosynostosis (CS) is a complex condition consisting of the early fusion of one or more cranial sutures in the intrauterine stage. The affected infant exhibits abnormal head shape at time of birth or shortly thereafter. It can be observed in normal individuals (non-syndromic CS or NSCS) or as a part of a multisystem syndrome. The purposes of the present article were to carry out a scoping review on Non-Syndromic CS and to discuss the most important findings retrieved. Material and Methods The steps of this scoping review were as follows: first, to pose a research question; second, to identify relevant studies to answer the research question; third, to select and retrieve the s…
FGFR2mutation in 46,XY sex reversal with craniosynostosis
2015
Patients with 46,XY gonadal dysgenesis (GD) exhibit genital anomalies, which range from hypospadias to complete male-to-female sex reversal. However, a molecular diagnosis is made in only 30% of cases. Heterozygous mutations in the human FGFR2 gene cause various craniosynostosis syndromes including Crouzon and Pfeiffer, but testicular defects were not reported. Here, we describe a patient whose features we would suggest represent a new FGFR2-related syndrome, craniosynostosis with XY male-to-female sex reversal or CSR. The craniosynostosis patient was chromosomally XY, but presented as a phenotypic female due to complete GD. DNA sequencing identified the FGFR2c heterozygous missense mutatio…