P19.04: Brain focal polygyria in thanatophoric dysplasia by ultrasound at 17–18 weeks of gestation: two case reports

Abstract

Thanatophoric Dysplasia (TD) is caused by mutations of the fibroblast growth factor (FGF) receptor 3 gene (FGFR3), which results in constitutive activation of FGFR3 tyrosine kinase. We report two cases of TD with FGFR3 mutation, showing temporal overgrowth and disorganisation of the hippocampus. 36 year-old mother with two healthy children was referred at 18 weeks of gestation due to short limbs. Ultrasound demonstrated typical appearance of TD. Transvaginal brain scan revealed ventriculomegaly and abnormally serpentine appearance of temporal lobe with focal polygyria. Pregnancy was terminated at 21 weeks and autopsy was done. Brain appearance was exactly the same appearance detected by prenatal ultrasound. Genetic analysis revealed a point mutation at c.1948 A → A/G, K650E in the exon 14 of FGFR3. 30 year-old mother visited our institute at 17 weeks of gestation due to nuchal edema and short limbs pointed out by previous doctor. Sonography showed quite similar appearance to case 1. Brain ventriculomegaly and focal polygyria in the temporal lobe was depicted and furthermore bidirectional power Doppler demonstrated brain surface blood vessels exactly along with serpentine polygyric brain. Pregnancy was terminated at 21 weeks and autopsy was done. Brain appearance was exactly the same appearance detected by prenatal ultrasound. Genetic analysis revealed a point mutation at c.1948 A → A/G, K650E in the exon 14 of FGFR3. It has been suggested that FGFR3 activation perturbs areal patterning, progenitor proliferation and apoptosis in cortical development. Phenotypes of migration disorder has been considered as after 7 gestational month. From our cases, however, focal polygyria and overgrown temporal lobe were already formed at the gestational age of 17 or 18 weeks. Considering timing of migration is between 3 and 5 months, focal polygyria formation seen in TD is quite earlier than other migration disorders because of loss of normal FGFR3 expression.