Developmental Disorders

Question 1

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.

Answer 1

Anencephaly

Question 2

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.

Answer 2

Encephalocele

Question 3

Failure of the posterior neuropore to form.
Herniation of CSF-filled sac, consisting of only the meninges - but NO NEURONAL TISSUE.

Answer 3

Meningocele

Question 4

Failure of the posterior neuropore to form.
Herniation of neuronal elements covered by meningeal sac.

Answer 4

Myelomeningocele

Question 5

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.

Answer 5

Chiari Type 1 Malformation

Question 6

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)

Answer 6

Chiari Type 2 Malformation

Question 7

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)

Answer 7

Chiari Type 3 Malformation

Question 8

Associated with maternal hyperthermia/fever on Days 20-26.
Characterized by Encephalocele, Microcephaly, Micro-ophthalmia, Cleft Lip, Polydactyly, Polycystic Kidneys, Ambiguous genitalia

Answer 8

Meckel’s Syndrome

Question 9

Associated with Diabetic Mothers.
Dysraphic sacrum and coccyx with atrophic muscle and bone.
Symptoms: Delayed sphincter control, walking, pes cavus, leg asymmetry

Answer 9

Caudal Regression Syndrome

Question 10

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)

Answer 10

Holoprosencephaly

Question 11

What disorders present with Agenesis of the Corpus Callosum?

Answer 11

Holoprosencephaly
Absent Septum Pellucidum
Schizencephaly
Septo-Optic Dysplasia
Aicardi Syndrome
Dandy-Walker Malformation

Question 12

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.

Answer 12

Septo-Optic Dysplasia

Question 13

X-linked Dominant
Agenesis of the Corpus Callosum
Chorioretinal Lacunes

Answer 13

Aicardi Syndrome

Question 14

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.

Answer 14

Dandy-Walker Syndrome

Question 15

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)

Answer 15

Lissencephaly

Question 16

Few or no gyri caused by a defect of radial cell migration

Answer 16

Type 1 Classic Lissencephaly
Miller-Diecker Syndrome

Question 17

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

Answer 17

Type 2 Lissencephaly

Question 18

Few broad thick gyri

Answer 18

Pachygyria

Question 19

Too many small gyri.
Associated with:
- Zellweger Syndrome (Cerebrohepatorenal Syndrome)
- AR Peroxisomal Disorder (Chromosome 13)

Answer 19

Polymicrogyria

Question 20

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.

Answer 20

Heterotopias

Question 21

Agenesis of only the Olfactory Bulb and Tract

Answer 21

Arrhinecephaly

Question 22

Septum Pellucidum is not fused

Answer 22

Cavum Septum Pellucidum

Question 23

Disorders of Neuronal Proliferation

Answer 23

Megalencephaly
Focal Cortical Dysplasia

Question 24

Disorders of Neuronal Migration

Answer 24

Lissencephaly - Agyria, Pachygyria, Subcortical Band Heterotopia
Cobblestone Complex Malformation
Heterotopias - Periventricular Nodular Heterotopias

Question 25

Disorders of Cortical Organization

Answer 25

Polymicrogyria
Focal Cortical Dysplasia with normal cell types
Microdysgenesis
Schizencephaly

Question 26

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

Answer 26

Periventricular Nodular Heterotopia

Question 27

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.

Answer 27

Focal Cortical Dysplasia

Question 28

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

Answer 28

Miller-Dieker Syndrome

Question 29

Mutations in DCX gene on chromosome X.
Encodes for protein doublecortin - involved in microtubule organization & stabilization

Answer 29

X-linked Lissencephaly

Question 30

Mutations in DCX gene on chromosome X.
Encodes for protein doublecortin - involved in microtubule organization & stabilization

Answer 30

X-linked Lissencephaly

Question 31

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

Answer 31

Schizencephaly

Question 32

CSF-filled cysts lined by WM or gliosis.
Result from in utero infections

Answer 32

Porencephaly