Developmental Neuropathology
Chapter 2: Midline Patterning Defects
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Cyclopia: single orbit with single or partially divided eye
Ethmocephaly: separate but closely spaced orbits with proboscis
Cebocephaly: ocular hypotelorism with single-nostril nose




Atelencephaly: absence of the telencephalon with some remaining diencephalic derivatives
Aprosencephaly: loss of the diencephalic and telencephalic structures

These are different from anencephaly due to the presence of a skin-covered skull, although hypoplastic.

Synonyms include Garcia-Lurie syndrome, atelencephalic microcephaly syndrome, XK syndrome, and XK-aprosencephaly syndrome.

Associated with other malformations including congenital heart disease (VSD, ASD, PDA, coarctation of the aorta), limb malformations (thumb hypoplasia/aplasia, oligodactyly, fan-shaped toes, syndactyly, clubfoot, single palmar crease), eye abnormalities (cyclopia, coloboma, hypertelorism, downslanting palpebral fissures, blepharophimosis, microphthalmia, microcornea), vertebral body defects, and genital defects. Usually lethal, or else severe growth and mental retardation.

These are very rare, and chromosomal abnormalities have been associated.

Agenesis of the Corpus Callosum

If found incidentally, can have very subtle deficits on neuropsychological testing, not always disconnection syndromes. Higher incidence of seizures and mental retardation. Believed that the clinical manifestations reflect more associated CNS anomalies than the lack of corpus callosum itself.

Associated metabolic disorders to consider include Smith-Lemli-Optiz syndrome, non-ketotic hyperglycinemia, infantile lactic acidosis associated with pyruvate carboxylase or PDH deficiency, Zellweger syndrome.

Pathogenesis is unclear. Corpus callosum forms from tghe commisural plate of the lamina terminalis between 40-43 days gestation, growing rostral to caudal. Can be caused by axon guidance defects, projection neuron specification defects, and midline glial defects.

Septo-optic Dysplasia

Absence of the septum pellucidum with hypoplastic optic nerves. Constellation known as De Morsier syndrome.

Clinical presentation includes visual impairment, hypothalamic-pituitary insufficency (symptomatic hypoglycemia, diabetes insipidus, growth hormone deficiency), seizures, cognitive retardation (or normal).

Can be associated with porencephaly. Some patients have mutations in HESX1. There can be associated retinal dysplasias or dysplasia of the lateral geniculate nucleus. Heterotopia, polymicrogyria can also be associated.

Other Midline Defects

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