Developmental Disorders Flashcards
Failure of the anterior neuropore to closed.
Absence of both cerebral hemispheres and variable portions of the brainstem.
Area Cerebrovasculosa - red shiny membranous mass at the skull base.
Anencephaly
Anterior Neuropore defect.
Herniation (protrusion) of brain tissue through midline skull defects.
The defect is always covered by a full-thickness skin, believed to develop after closure of the neural tube.
Encephalocele
Failure of the posterior neuropore to form.
Herniation of CSF-filled sac, consisting of only the meninges - but NO NEURONAL TISSUE.
Meningocele
Failure of the posterior neuropore to form.
Herniation of neuronal elements covered by meningeal sac.
Myelomeningocele
Kinked cervical cord, Brainstem elongation, Cerebellar tonsillar dysmorphic tissue displaced downward (>5 mm below foramen magnum), Beaked mesencephalic tectum, Atretic aqueduct, Small cerebellum with small posterior fossa and large foramen magnum.
Chiari Type 1 Malformation
Kinked cervical cord, Brainstem elongation, Cerebellar tonsillar dysmorphic tissue displaced downward (>5 mm below foramen magnum), Beaked mesencephalic tectum, Atretic aqueduct, Small cerebellum with small posterior fossa and large foramen magnum.
+ Lumbar Spinal Fusion Defect (with Myelomeningocele and Hydrocephals)
Chiari Type 2 Malformation
Kinked cervical cord, Brainstem elongation, Cerebellar tonsillar dysmorphic tissue displaced downward (>5 mm below foramen magnum), Beaked mesencephalic tectum, Atretic aqueduct, Small cerebellum with small posterior fossa and large foramen magnum.
+ Lumbar Spinal Fusion Defect (with Myelomeningocele and Hydrocephals)
+ Occipital Encephalocele or Myelocerebellomeningocele (2/2 to Cervical Spina Bifida)
Chiari Type 3 Malformation
Associated with maternal hyperthermia/fever on Days 20-26.
Characterized by Encephalocele, Microcephaly, Micro-ophthalmia, Cleft Lip, Polydactyly, Polycystic Kidneys, Ambiguous genitalia
Meckel’s Syndrome
Associated with Diabetic Mothers.
Dysraphic sacrum and coccyx with atrophic muscle and bone.
Symptoms: Delayed sphincter control, walking, pes cavus, leg asymmetry
Caudal Regression Syndrome
Failure of the forebrain to separate into two hemispheres resulting in a single-lobed cerebrum and only one ventricle.
Associated with anosmia, Ethmocephaly (hypertelorism with proboscis between eyes), Cebocephaly (single nostril), Cyclopia, Cleft Lip, Hypoplastic Optic Nerves.
Associated Chromosomal Abnormalities: Trisomy 13 (Patau Syndrome), Trisomy 18 (Edwards Syndrome)
Holoprosencephaly
What disorders present with Agenesis of the Corpus Callosum?
Holoprosencephaly
Absent Septum Pellucidum
Schizencephaly
Septo-Optic Dysplasia
Aicardi Syndrome
Dandy-Walker Malformation
Absent Septum Pellucidum
Hypoplastic Optic Nerves & Optic Chiasm
Dysgenesis of the Corpus Callosum + Anterior Commissure
Fornix detachment from the Corpus Callosum
Shizencephaly
Pituitary axis dysfunction
Mutations in HESX1, Homeobox, SOX genes.
Septo-Optic Dysplasia
X-linked Dominant
Agenesis of the Corpus Callosum
Chorioretinal Lacunes
Aicardi Syndrome
Failure of the development of the Foramen of Magendie.
Cystic dilation of the 4th Ventricle and cerebellar vermis agenesis with enlarged posterior fossa.
Elevation of the inion.
Agenesis of the Corpus Callosum.
Dandy-Walker Syndrome
Malformation of cortical development from abnormal neuronal migrations resulting in impaired gyri formation
Few or No gyri resulting in a SMOOTH BRAIN
In the classic form the cortex is thick but consists only of 4 layers (as opposed to the normal 6 neocortical layers)
Lissencephaly
Few or no gyri caused by a defect of radial cell migration
Type 1 Classic Lissencephaly
Miller-Diecker Syndrome
Few or No gyri resulting in a SMOOTH BRAIN
Due to an over migration of neurons beyond the disrupted basal membrane and pial surface (Cajal-Retzius Layer) onto the overlying subarachnoid tissue.
Migrating Cells breakthrough the limiting pia mater in an irregular fashion forming a thick cobble-stone appearance
Path: Cortex has no recognizable layers, dysplastic and thick
Presents: Microcephaly, Seizures, Global Developmental Delay, Hypotonia, Muscular Dystrophy
Associated with Walker-Warburg Syndrome, Fukuyama Muscular Dystrophy, Muscle-Eye-Brain Disease of Santavuori
Type 2 Lissencephaly
Few broad thick gyri
Pachygyria
Too many small gyri.
Associated with:
- Zellweger Syndrome (Cerebrohepatorenal Syndrome)
- AR Peroxisomal Disorder (Chromosome 13)
Polymicrogyria
Collections of ectopic neurons located outside the cortex secondary to arrested radial migration.
Appear as islands of gray matter located in abnormal places.
Neurons have normal morphology.
Heterotopias
Agenesis of only the Olfactory Bulb and Tract
Arrhinecephaly
Septum Pellucidum is not fused
Cavum Septum Pellucidum
Disorders of Neuronal Proliferation
Megalencephaly
Focal Cortical Dysplasia
Disorders of Neuronal Migration
Lissencephaly - Agyria, Pachygyria, Subcortical Band Heterotopia
Cobblestone Complex Malformation
Heterotopias - Periventricular Nodular Heterotopias
Disorders of Cortical Organization
Polymicrogyria
Focal Cortical Dysplasia with normal cell types
Microdysgenesis
Schizencephaly
Disorder of Neuronal Migration
X-linked Dominant
Mutations FLNA gene (FILAMIN A) on chromsome X - Encodes for protein involved in cytoskeleton stabilization & focal adhesions. Abnormalities in this protein lead to disruption in cell migration by impeding the attachment of neurons to radial glia.
Nodules of gray matter line the ventricles and extending to the lumen.
Presentation: Seizures
Periventricular Nodular Heterotopia
Cortical malformations comprised of abnormal cells (dysmorphic, enlarged neurons, Balloon Cells) and abnormal lamination.
In the setting of Tuberous Sclerosis.
Hallmark: Balloon Cells - Proliferation of abnormal cells within the Germinal Matrix.
Focal Cortical Dysplasia
Four-layer variant of Lissencephaly (abnormal neuronal migration resulting impaired formation of gyri).
Microdeletions on chromosome 17 in the LIS1 gene: Encodes for protein involved in regulation of microtubules and dynein function, mutations interfere with microtubule-directed migration of neurons from the ventricular zone
Microcephaly, Micrognathia, Low-set Ears, Thin upper lip, Short nose with upturned nares, prominent Forehead, Bitemporal hollowing
Developmental delay, Hypotonia, Spasticity, Seizures
Miller-Dieker Syndrome
Mutations in DCX gene on chromosome X.
Encodes for protein doublecortin - involved in microtubule organization & stabilization
X-linked Lissencephaly
Mutations in DCX gene on chromosome X.
Encodes for protein doublecortin - involved in microtubule organization & stabilization
X-linked Lissencephaly
Cleft Brain: Deep cleft lined with uniformly GM that extends from the pial surface to the ventricle is lined with cortex.
Associated with Septo-Optic Dysplasia
Associated with mutations of Homeobox gene EMX2
Schizencephaly
CSF-filled cysts lined by WM or gliosis.
Result from in utero infections
Porencephaly
