Hypochondroplasia, achondroplasia, and thanatophoric dysplasia are related at the molecular level, all caused by fibroblast growth factor receptor 3 (FGFR3) gene mutations. They differ in severity. FGFR3 has critical roles in fibroblast growth factor (FGF) signalling pathways during bone growth and cerebral cortical development. Mutations of the FGFR3 gene lead to constitutive activation of FGFR3. The well-described brain malformation in thanatophoric dysplasia is characterized by gross abnormalities of temporal lobe patterning and severe dysplasia of the hippocampus. Experimental models suggest that increased proliferation, abnormal migration, and decreased apoptosis are involved. However, reports of the brain findings in hypochondroplasia are based solely on radiologic imaging.
We present the neuropathology of a 44 year-old man with hypochondroplasia, epilepsy, and significant intellectual disability. The temporal lobes are enlarged, prominent fissures traverse the inferior temporal surface, and the hippocampus is abnormally folded. Microscopically, the dentate gyrus is variably small or thin and is located near the edge of a gyrus. Ammon’s horn is displaced and meandering. Subicular-like clusters are profuse. Complex gyri resemble microgyria. White matter forms a subpial border in some gyri. In summary: medial temporal lobe dysgenesis.
This individual also had many autistic features including stereotypies and head banging. The latter could explain another surprising set of brain abnormalities unrelated to the presumed FGFR3-related syndrome.
This presentation will enable the learner to:
- 1.Summarize current theories on the pathogenesis of FGFR3-related cortical malformation
- 2.Describe the brain abnormalities in hypochondroplasia
- 3.Identify the neuropathology resulting from head banging