disorders - tut 3 Flashcards
(Primary) Microcephaly
Proliferation / Neurogenesis
Characterized by reduced brain growth Imbalance of progenitor production and cell death
Types: Primary (before birth), and
secondary (after birth)
Can be presented with other defects ex. autism spectrum disorder (ASD)
Mutations in the
following genes:
ASPM gene
MCPH1 gene
CENPJ
WDR62
nongenetic factors:
Influenza
Herpes
Viral infections
Alcohol
Parasitic
infections
Periventricular heterotopia (PH)
Neuronal migration
Heterotopic nodules are composed of disorganized neurons along the lateral ventricles of the brain. Associated with connective tissue disorder, Ehlers-Danlos syndrome (EDS) which is characterized by joint
and skin hyperextensibility and vascular problems (aortic dissection, excess bleeding, easily bruised)
Genes carrying mutations:
Filamin A–encodes actin binding protein which regulates cytoskeleton and cell motility
ARFGEF2–encodes brefeldin-inhibited
guanine exchange factor 2 protein
no non genetic factors
(Classic/ Type 1) Lissencephaly
Neuronal migration in early gestation to late gestation (most
of fetal development stage)
The typical folds of the brain (sulci and gyri) are missing, leading to a
smooth-brain appearance.
The genes that carry mutations:
-LIS1 (whose product regulates
transport along the microtubule
dynein.)
-DCX (x-linked so in men results in
complete lissencephaly and in women results in ectopic neuronal
layering. The product of this gene
regulates microtubule stability and
signalling during migration.)
Infection by cytomegalovirus has been thought to be a non-genetic
contribution to lissencephaly.
Lack of oxygenated blood to the brain during fetal development
Agenesis of corpus callosum
(ACC)
Neuronal Migration (Interneuron
Development) Connectivity is
affected
Partial absence/abnormal development of the corpus callosum
(connects the two cerebral hemispheres) or abnormal
development of the
corpus callosum
(connects the two
cerebral hemispheres)
or abnormal development of the
corticospinal tract (carries cortical
information to the spinal cord). This is caused by errors in axonal projection. Can’t cross midline, form
but dont cross. Connectivity fails to
form.
Mutations in the disrupted-in-schizo
phrenia 1 (DISC1) gene located at
1q42. Chromosomal rearrangements - e.g. trisomies 18, 13, 21 del(4)(p16),
del(6)(q23), dup(8)(p21p23),
dup(11)(q23qter).
Duplications, deletions on
chromosomes
Maternal alcohol use during
pregnancy, Maternal
phenylketonuria, Chiari II
malformation, Viral infection
(influenza, virus during pregnancy)
