Ellis-van Creveld Syndrome with Sagittal Craniosynostosis.
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ABSTRACT:
SUBMITTER: Fischer AS
PROVIDER: S-EPMC4428735 | biostudies-other | 2015 Jun
REPOSITORIES: biostudies-other
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Project description:PurposeNumerous classification systems of nonsyndromic sagittal craniosynostosis (NSC) are applied but none has gained a wide acceptance, since each classification is focused on distinct aspects of cranial dysmorphology. The goal of this study was to depict the most common combinations of radiomorphologic characteristics of NSC and to separate groups where the patients were morphologically similar to one another and at the same time significantly different from others.MethodsThe study was conducted on anonymized thin-cut CT scans of 131 children with NSC aged 1-12 months (mean age 5.42 months). The type of cranial dysmorphology was assessed using four criteria: skull shape, pattern of sagittal suture fusion, morphologic features and cerebrospinal fluid (CSF) spaces alterations. After assigning the categories, an unsupervised k-modes clustering algorithm was applied to identify distinct patients clusters representing radiomorphologic profiles determined by investigated characteristics.ResultsCluster analysis revealed three distinct radiomorphologic profiles including the most common combinations of features. The profiles were not influenced by sex nor age but were significantly determined by skull shape (V = 0.58, P < 0.0001), morphologic features (V = 0.50, P < 0.0001) and pattern of sagittal suture fusion (V = 0.47, P < 0.0001). CSF alterations did not significantly correlate with the profiles (P = 0.3585).ConclusionNSC is a mosaic of radiologic and morphologic features. The internal diversity of NSC results in dissimilar groups of patients defined by unique combinations of radiomorphologic characteristics, from which the skull shape is the most differentiating factor. Radiomorphologic profiles support the idea of clinical trials targeted at more selective outcomes assessment.
| S-EPMC10643241 | biostudies-literature
Project description:Early fusion of the sagittal suture is a clinical condition called, sagittal craniosynostosis. Calvarial reconstruction is the most common treatment option for this condition with a range of techniques being developed by different groups. Computer simulations have a huge potential to predict the calvarial growth and optimise the management of this condition. However, these models need to be validated. The aim of this study was to develop a validated patient-specific finite element model of a sagittal craniosynostosis. Here, the finite element method was used to predict the calvarial morphology of a patient based on its preoperative morphology and the planned surgical techniques. A series of sensitivity tests and hypothetical models were carried out and developed to understand the effect of various input parameters on the result. Sensitivity tests highlighted that the models are sensitive to the choice of input parameter. The hypothetical models highlighted the potential of the approach in testing different reconstruction techniques. The patient-specific model highlighted that a comparable pattern of calvarial morphology to the follow up CT data could be obtained. This study forms the foundation for further studies to use the approach described here to optimise the management of sagittal craniosynostosis.
| S-EPMC6949270 | biostudies-literature
Project description:INTRODUCTION:Latent cranial suture fusions may present with mild or absent phenotypic changes that make the clinical diagnosis challenging. Recent reports describe patients with sagittal synostosis and a normal cranial index (CI), a condition termed normocephalic sagittal craniosynostosis (NSC). The goal of this study is to evaluate the shape and intracranial volume (ICV) in a cohort of NSC patients using quantitative cranial shape analysis (CSA). METHODS:We identified 19 patients (7.5 ± 2.28 years) between 2011 and 2016, who presented to our hospital with NSC. Cranial index and CSA were measured from the computed tomography image. Cranial shape analysis calculates the distances between the patient's cranial shape and its closest normal shape. Intracranial volume was measured and compared to an established age-matched normative database. RESULTS:Cranial index revealed 15 (78.9%) patients within the mesocephalic range and 4 patients (21.1%) in the brachycephalic range. Detailed CSA identified 15 (78.9%) patients with subtle phenotypic changes along the scaphocephalic spectrum (ie, subtle anterior and posterior elongation with inter-parietal narrowing) and 1 patient (5.3%) with isolated overdevelopment on the posterior part of the right parietal bone. Three patients (15.8%) had a CSA close to normal. Mean ICV was 1410.5 ± 192.77cc; most patients (78.9%) fell within ±2 standard deviations. CONCLUSION:Quantitative CSA revealed that most of the patients with NSC had cranial shape abnormalities, consistent with a forme fruste scaphocephaly that could not be otherwise recognized by clinical observation or CI. Given these findings, we propose the term occult scaphocephaly to describe this condition. The associated incidence of intracranial hypertension is unknown.
| S-EPMC7343588 | biostudies-literature
Project description:Ulnar-mammary syndrome (UMS) is a rare, autosomal dominant disorder characterized by anomalies affecting the limbs, apocrine glands, dentition, and genital development. This syndrome is caused by haploinsufficiency in the T-Box3 gene (TBX3), with considerable variability in the clinical phenotype being observed even within families. We describe a one-year-old female with unilateral, postaxial polydactyly, and bilateral fifth fingernail duplication. Next-generation sequencing revealed a novel, likely pathogenic, variant predicted to affect the canonical splice site in intron 3 of the TBX3 gene (c.804 + 1G > A, IVS3 + 1G > A). This variant was inherited from the proband’s father who was also diagnosed with UMS with the additional clinical finding of congenital, sagittal craniosynostosis. Subsequent whole genome analysis in the proband’s father detected a variant in the EFNA4 gene (c.178C > T, p.His60Tyr), which has only been reported to be associated with sagittal craniosynostosis in one patient prior to this report but reported in other cranial suture synostosis. The findings in this family extend the genotypic spectrum of UMS, as well as the phenotypic spectrum of EFNA4-related craniosynostosis.
| S-EPMC9498434 | biostudies-literature
Project description:BACKGROUND:Craniosynostosis is a condition that includes the premature fusion of one or multiple cranial sutures. Among various craniosynostosis forms, sagittal nonsyndromic craniosynostosis is the most prevalent. Although different gene mutations have been identified in some craniosynostosis syndromes, the cause of sagittal nonsyndromic craniosynostosis remains largely unknown. METHODS:To screen for candidate genes for sagittal nonsyndromic craniosynostosis, the authors sequenced DNA of 93 sagittal nonsyndromic craniosynostosis patients from a population-based study conducted in Iowa and New York states. FGFR1-3 mutational hotspots and the entire TWIST1, RAB23, and BMP2 coding regions were screened because of their known roles in human nonsyndromic or syndromic sagittal craniosynostosis, expression patterns, and/or animal model studies. RESULTS:The authors identified two rare variants in their cohort. A FGFR1 insertion c.730_731insG, which led to a premature stop codon, was predicted to abolish the entire immunoglobulin-like III domain, including the ligand-binding region. A c.439C>G variant was observed in TWIST1 at its highly conserved loop domain in another patient. The patient's mother harbored the same variant and was reported with jaw abnormalities. These two variants were not detected in 116 alleles from unaffected controls or seen in the several databases; however, TWIST1 variant was found in a low frequency of 0.000831 percent in Exome Aggregation Consortium database. CONCLUSIONS:The low mutation detection rate indicates that these genes account for only a small proportion of sagittal nonsyndromic craniosynostosis patients. The authors' results add to the perception that sagittal nonsyndromic craniosynostosis is a complex developmental defect with considerable genetic heterogeneity. CLINICAL QUESTION/LEVEL OF EVIDENCE:Risk, II.
| S-EPMC4770826 | biostudies-literature
Project description:The neonate skull consists of several bony plates, connected by fibrous soft tissue called sutures. Premature fusion of sutures is a medical condition known as craniosynostosis. Sagittal synostosis, caused by premature fusion of the sagittal suture, is the most common form of this condition. The optimum management of this condition is an ongoing debate in the craniofacial community while aspects of the biomechanics and mechanobiology are not well understood. Here, we describe a computational framework that enables us to predict and compare the calvarial growth following different reconstruction techniques for the management of sagittal synostosis. Our results demonstrate how different reconstruction techniques interact with the increasing intracranial volume. The framework proposed here can be used to inform optimum management of different forms of craniosynostosis, minimising the risk of functional consequences and secondary surgery.
| S-EPMC9170984 | biostudies-literature
Project description:Craniosynostosis (CS) is a major birth defect in which one or more skull sutures fuse prematurely. We previously performed a genome-wide association study (GWAS) for sagittal non-syndromic CS (sNCS), identifying associations downstream from BMP2 on 20p12.3 and intronic to BBS9 on 7p14.3; analyses of imputed variants in DLG1 on 3q29 were also genome-wide significant. We followed this work with a GWAS for metopic non-syndromic NCS (mNCS), discovering a significant association intronic to BMP7 on 20q13.31. In the current study, we sequenced the associated regions on 3q29, 7p14.3, and 20p12.3, including two candidate genes (BMP2 and BMPER) near some of these regions in 83 sNCS child-parent trios, and sequenced regions on 7p14.3 and 20q13.2-q13.32 in 80 mNCS child-parent trios. These child-parent trios were selected from the original GWAS cohorts if the probands carried at least one copy of the top associated GWAS variant (rs1884302 C allele for sNCS; rs6127972 T allele for mNCS). Many of the variants sequenced in these targeted regions are strongly predicted to be within binding sites for transcription factors involved in craniofacial development or bone morphogenesis. Variants enriched in more than one trio and predicted to be damaging to gene function are prioritized for functional studies.
| S-EPMC9141801 | biostudies-literature
Project description:PurposeThe aim of this study was to investigate the biomechanics of endoscopically assisted strip craniectomy treatment for the management of sagittal craniosynostosis while undergoing three different durations of postoperative helmet therapy using a computational approach.MethodsA previously developed 3D model of a 4-month-old sagittal craniosynostosis patient was used. The strip craniectomy incisions were replicated across the segmented parietal bones. Areas across the calvarial were selected and constrained to represent the helmet placement after surgery. Skull growth was modelled and three variations of helmet therapy were investigated, where the timings of helmet removal alternated between 2, 5, and 8 months after surgery.ResultsThe predicted outcomes suggest that the prolonging of helmet placement has perhaps a beneficial impact on the postoperative long-term morphology of the skull. No considerable difference was found on the pattern of contact pressure at the interface of growing intracranial volume and the skull between the considered helmeting durations.ConclusionAlthough the validation of these simulations could not be performed, these simulations showed that the duration of helmet therapy after endoscopically assisted strip craniectomy influenced the cephalic index at 36 months. Further studies require to validate these preliminary findings yet this study can lay the foundations for further studies to advance our fundamental understanding of mechanics of helmet therapy.
| S-EPMC10160196 | biostudies-literature
Project description:Sagittal craniosynostosis (CS) is a pathologic condition that results in premature fusion of the sagittal suture, restricting the transverse growth of the skull leading in some cases to elevated intracranial pressure and neurodevelopmental delay. There is still much to be learned about the etiology of CS. Here, we report a case of 56-year-old male cadaver that we describe as sagittal CS with torus palatinus being an additional anomaly. The craniotomy was unsuccessful (cephalic index, CI = 56) and resulted in abnormal vertical outgrowth of the craniotomized bone strip. The histological analysis of the latter revealed atypical, noncompensatory massive bone overproduction. Exome sequencing of DNA extracted from the cadaveric tissue specimen performed on the Next Generation Sequencing (NGS) platform yielded 81 genetic variants identified as pathologic. Nine of those variants could be directly linked to CS with five of them targeting RhoA GTPase signaling, with a potential to make it sustained in nature. The latter could trigger upregulated calvarial osteogenesis leading to premature suture fusion, skull bone thickening, and craniotomized bone strip outgrowth observed in the present case.
| S-EPMC6925784 | biostudies-literature
Project description:Premature closure of the sagittal suture occurs as an isolated (nonsyndromic) birth defect or as a syndromic anomaly in combination with other congenital dysmorphologies. The genetic causes of sagittal nonsyndromic craniosynostosis (NSC) remain unknown. Although variation of the dysmorphic (scaphocephaly) skull shape of sagittal NSC cases has been acknowledged, this variation has not been quantitatively studied three-dimensionally (3D). We have analyzed the computed tomography skull images of 43 infants (aged 0.9-9 months) with sagittal NSC using anatomical landmarks and semilandmarks to quantify and characterize the within-sample phenotypic variation. Suture closure patterns were defined by dividing the sagittal suture into three sections (anterior, central, posterior) and coding each section as 'closed' or 'fused'. Principal components analysis of the Procrustes shape coordinates representing the skull shape of 43 cases of NSC did not separate individuals by sex, chronological age, or dental stages of the deciduous maxillary first molar. However, analysis of suture closure pattern allowed separation of these data. The central section of the sagittal suture appears to be the first to fuse. Then, at least two different developmental paths towards complete fusion of the sagittal suture exist; either the anterior section or the posterior section is the second to fuse. Results indicate that according to the sequence of sagittal suture closure patterns, different craniofacial complex shapes are observed. The relationship between craniofacial shape and suture closure indicates not only which suture fused prematurely (in our case the sagittal suture), but also the pattern of the suture closure. Whether these patterns indicate differences in etiology cannot be determined with our data and requires analysis of longitudinal data, most appropriately of animal models where prenatal conditions can be monitored.
| S-EPMC2913018 | biostudies-literature