title: Precocious synapses in 13.5-week fetal holoprosencephalic cortex and cyclopean retina.
abstract: BACKGROUND
  Genetic programming of cerebral development involves tissue morphogenesis and also timing of developmental processes. Precocious synaptogenesis in the neocortical plate was previously demonstrated in 5 of 6 fetuses of 20-31 weeks gestation.
  
  
  METHODS
  Neuropathological examination was performed of a 13-week-5-day fetus with trisomy-13, a lobar holoprosencephaly, hydrocephalus, cyclopia and absence of ears. Immunocytochemical demonstration of the synaptic vesicle protein synaptophysin was performed in the brain and retina, along with other neuronal markers.
  
  
  RESULTS
  Synaptophysin reactivity in the cortical plate was patchy and precocious. Radial glial fibres, demonstrated by vimentin, were oriented parallel to the cortical plate rather than perpendicular, probably because of hydrocephalus. A corpus striatum was not identified, but the poorly formed thalamus exhibited synaptophysin reactivity around many neurones. The cyclopean eye had ocular features of maturational delay including persistent hyaloid artery; ganglion cells were reduced in number, but retinal synaptophysin reactivity was paradoxically precocious.
  
  
  CONCLUSIONS
  Holoprosencephaly exhibits abnormal patchy synapse distribution in the neocortex and retina; synaptogenesis was precocious, as we previously described in older fetuses. Too soon an onset of synapse formation may promote early epileptic circuitry, leading to severe infantile epilepsies postnatally. The visual system is the last of the special sensory systems to mature, yet in this case showed too early synapse formation. In HPE, cyclopia and in trisomy 13, total absence of external ears has not been reported; it results from faulty craniofacial induction by neural crest.
authors: Department of Paediatrics, University of Calgary Faculty of Medicine and Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada; Department of Pathology (Neuropathology), University of Calgary Faculty of Medicine and Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada; Department of Clinical Neurosciences, University of Calgary Faculty of Medicine and Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada. Electronic address: harvey.sarnat@albertahealthservices.ca.
authors: Harvey B
authors: HB
authors: Sarnat
authors: Department of Pathology (Neuropathology), University of Calgary Faculty of Medicine and Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada.
authors: Lothar
authors: L
authors: Resch
authors: Department of Paediatrics, University of Calgary Faculty of Medicine and Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada; Department of Clinical Neurosciences, University of Calgary Faculty of Medicine and Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada.
authors: Laura
authors: L
authors: Flores-Sarnat
authors: Department of Pathology (Paediatric), University of Calgary Faculty of Medicine and Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada.
authors: Weiming
authors: W
authors: Yu
mesh_terms: D002540:Cerebral Cortex / Q000196:embryology / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005333:Fetus; D016142:Holoprosencephaly / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D010784:Photomicrography; D012160:Retina / Q000196:embryology / Q000378:metabolism / Q000473:pathology*; D013569:Synapses / Q000378:metabolism / Q000473:pathology*; D016708:Synaptophysin / Q000378:metabolism
chemical_list: C569014:SYP protein, human; D016708:Synaptophysin
keywords: Absent ears; Cyclopia; Holoprosencephaly; Human fetus; Hyaloid artery; Hydrocephalus; Neural crest; Precocious synaptogenesis; Trisomy-13