Type:
Educational Exhibit
Keywords:
Not applicable, Congenital, Education, MR, CT, Paediatric, Neuroradiology brain, Head and neck, Neuro
Authors:
A. D. F. Ferreira1, T. A. L. Freddi2, F. D. G. Dantas1, N. Ferreira1, H. B. Zuppani1, K. SAYEGH1, D. Costa1, A. Wolosker1, M. Borri1; 1Sao Paulo/BR, 2Sao Paulo, SP/BR
DOI:
10.26044/ecr2020/C-12591
Background
Thanatophoric dysplasia, achondroplasia, and hypochondroplasia belong to the fibroblast growth factor receptor 3 (FGFR3) group of genetic skeletal disorders and mutations on this gene are associated to MAPK signaling changes. Different allelic mutations result in the variable severity of expression. Fig. 3
There is a growing body of literature elucidating the role of FGFR3 mutations in neural and skeletal development. In embryonic tissues in mice, FGFR3 expression is limited principally to neural tube derivatives (developing brain and spinal cord), cartilage rudiments of developing bone, the cochlea, and the lens. All 4 fibroblast growth factor receptors are expressed in the developing brain and contribute to its development. The FGFR3 gene in mice is expressed in a gradient in the developing cortex, with the highest levels adjacent to the hippocampal primordia and cortical hem. Fibroblast growth factors bind to the fibroblast growth factor receptors, and this signaling is an important regulator of cerebral cortex development. Studies have demonstrated malformations involving the cerebral cortex, such as expansion of the occipitotemporal cortex and oversulcation of the mesiotemporal lobes in the presence of activating FGFR3 mutations, and more recently some studies have shown that fibroblast growth factor signaling also plays an important role in regulating the formation of the cerebellum from the early embryonic period into early postnatal life, justifying the presence of macrocerebellum in some of this patients.
The morphologic changes on the skull base in patients with FGFR3 related skeletal dysplasias may be determined by limited proliferation of chondrocytes and accelerated bone formation leading to early closure of synchondroses and skull base hypoplasia.