Rare and de novo coding variants in chromodomain genes in Chiari I malformation

Sadler, Brooke; Wilborn, Jackson; Antunes, Lilian; Kuensting, Timothy; Hale, Andrew T.; Gannon, Stephen; McCall, Kevin; Cruchaga, Carlos; Harms, Matthew B.; Voisin, Norine; Reymond, Alexandre; Cappuccio, Gerarda; Brunetti‐Pierri, Nicola; Tartaglia, Marco; Niceta, Marcello; Leoni, Chiara; Zampino, Giuseppe; Ashley–Koch, Allison; Urbizu, Aintzane; Garrett, Melanie E.; Soldano, Karen; Macaya, Alfons; Conrad, Donald F.; Strahle, Jennifer; Dobbs, Matthew B.; Turner, Tychele N.; Shannon, Chevis N.; Brockmeyer, Douglas L.; Limbrick, David D.; Gurnett, Christina A.; Haller, Gabe

doi:10.1016/j.ajhg.2020.12.015

Cited by 3 publications

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“…Although the causality of these genes has to be proved yet, this study suggests that CIM could arise from the action of different genes, the combination of which would explain the differences in the PCF morpho-volumetric analysis and the absence of a significant PCF hypoplasia in several CIM subjects compared to controls. Furthermore, a very recent multicenter study, based on the whole exome sequencing of 232 CIM families (668 patients), showed that chromodomain genes (namely, CHD3 and CHD8 genes) can contribute to CIM genesis [ 43 ]. These genes are implicated in macrocephaly (as it happens in zebrafishes), and macrocephaly (large head circumference without associated brain or CSF anomalies) was largely present in the families enrolled for this study.…”

Section: Impact Of Pcf Changes On Primary Chiari I Malformationmentioning

confidence: 99%

Functional and morphological changes in hypoplasic posterior fossa

et al. 2021

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Background The knowledge of the development and the anatomy of the posterior cranial fossa (PCF) is crucial to define the occurrence and the prognosis of diseases where the surface and/or the volume of PCF is reduced, as several forms of craniosynostosis or Chiari type I malformation (CIM). To understand the functional and morphological changes resulting from such a hypoplasia is mandatory for their correct management. The purpose of this article is to review the pertinent literature to provide an update on this topic. Methods The related and most recent literature addressing the issue of the changes in hypoplasic PCF has been reviewed with particular interest in the studies focusing on the PCF characteristics in craniosynostosis, CIM, and achondroplasia. Results and conclusions In craniosynostoses, namely, the syndromic ones, PCF shows different degrees of hypoplasia, according to the different pattern and timing of early suture fusion. Several factors concur to PCF hypoplasia and contribute to the resulting problems (CIM, hydrocephalus), as the fusion of the major and minor sutures of the lambdoid arch, the involvement of the basal synchondroses, and the occlusion of the jugular foramina. The combination of these factors explains the variety of the clinical and radiological phenotypes. In primary CIM, the matter is complicated by the evidence that, in spite of impaired PCF 2D measurements and theories on the mesodermal defect, the PCF volumetry is often comparable to healthy subjects. CIM is revealed by the overcrowding of the foramen magnum that is the result of a cranio-cerebral disproportion (altered PCF brain volume/PCF total volume). Sometimes, this disproportion is evident and can be demonstrated (basilar invagination, real PCF hypoplasia); sometimes, it is not. Some recent genetic observations would suggest that CIM is the result of an excessive growth of the neural tissue rather than a reduced growth of PCF bones. Finally, in achondroplasia, both macrocephaly and reduced 2D and 3D values of PCF occur. Some aspects of this disease remain partially obscure, as the rare incidence of hydrocephalus and syringomyelia and the common occurrence of asymptomatic upper cervical spinal cord damage. On the other hand, the low rate of CIM could be explained on the basis of the reduced area of the foramen magnum, which would prevent the hindbrain herniation.

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Section: Impact Of Pcf Changes On Primary Chiari I Malformationmentioning

confidence: 99%