Chapter 18 Flashcards
Most defects of the spinal cord result from abnormal closure of the neural folds in the third and fourth weeks of development. The resulting abnormalities, ____, may involve the meninges, vertebrae, muscles, and skin.
neural tube defects [NTDs]
_____ is a general term for NTDs affecting the spinal region. It consists ofa splitting of the vertebral arches and may or may not involve underlying neural tissue
Spina bifida
___ is a defect in the vertebral arches that is covered by skin and normally does not involve underlying neural tissue
Spina bifida occulta
Occasionally, the neural folds do not elevate but remain as a flattened mass of neural tissue [spina bifida with myeloschisis or ____]
rachischisis
In some cases, only fluid filled meninges protrude through the defect [____]; in others, neural tissue is included in the sac [___]
meningocele - myelomeningocele
___ requiring intervention develops in 80% to 90% of children born with severe NTDs and is often related to the presence of an ____ [herniation of part of the cerebellum into the foramen magnum], which obstructs the flow of cerebrospinal fluid and causes the hydrocephalus.
Hydrocephaly - Arnold-Chiari malformation
The origin of most NTDs is multifactorial, and the likelihood of having a child with such a defect increases significantly once one affected offspring is ___
born
Prevention of many NTDs is possible if women take ___ starting at least 1 month prior to conception and then throughout their pregnancy. Such a protocol reduces the occurrence of NTDs by as much as 50% to 70%.
folic acid [400 ug/day]
Occasionally, a small portion of Rathke pouch persists in the roof of the pharynx as a ___.
pharyngeal hypophysis
Folic acid may also reduce the incidence of ___. Because approximately 50% of all pregnancies are unplanned, it is recommended that all women of childbearing age take a multivitamin containing 400 ug of folic acid daily
autism spectrum disorder [ASD]
___ arise from remnants of Rathke pouch. They may form within the sella turcica or along the stalk of the pituitary but usually lie above the sella. They may cause hydrocephalus and pituitary dysfunction [e.g., diabetes insipidus, growth failure]
Craniopharyngiomas
_____ refers to a spectrum of abnormalities in which a loss of midline structures results in malformations of the brain and face
Holoprosencephaly [HPE]
In severe cases, the lateral ventricles merge into a single ___the eyes are fused, and there is a single nasal chamber along with other midline facial defects
telencephalic vesicle [alobar HPE],
Mutations in ___, the gene that regulates establishment of the ventral midline in the CNS, result in some forms of HPE
SHH
Another cause is defective ____ leading to
_____
cholesterol biosynthesis - Smith-Lemli-Opitz syndrome
These children have craniofacial and limb defects, and 5% have HPE. Smith—Lemli - Opitz syndrome is an autosomal recessive condition due to abnormalities in ____, which metabolizes 7-dehydrocholesterol to cholesterol
7-dehydrocholesterol reductase
Other genetic causes include mutations in the transcription factors ____, ___, and the ___
SINE OCULIS HOMEOBOX 3 [SIX3] - TG-INTERACTING FACTOR [TGIF] - ZINC FINGER PROTEIN [ZIC2]
____ is a rare disorder in which large clefts occur in the cerebral hemispheres, sometimes causing a loss of brain tissue. Mutations in the homeobox gene ___ appear to account for some of these cases.
Schizencephaly - EMX2
Ossification defects in bones of the skull can result in ____, ____, and ___
meningoceles - meningoencephallocates - meningohydroencephalceles
If the opening of the occipital bone is small, only meninges bulge through it [___], but if the defect is large, part of the brain and even part of the ventricle may penetrate through the opening into the meningeal sac
meningocele
The latter two malformations are known as ___ and ___, respectively. These defects occur in 1/12,000 births
meningoencephalocele - meningohydroencephocele
___ is characterized by failure of the cephalic part of the neural tube to close. As a result, the vault of the skull does not form, leaving the malformed brain exposed.
Exencephaly
Later, this tissue degenerates, leaving a mass of necrotic tissue. This defect is called ___, although the brainstem remains intact
anencephaly
In some cases, the closure defect of the neural tube extends caudally into the spinal cord, and the abnormality is called
____
craniorachischisis
Because anencephalic fetuses lack a swallowing reflex, the last 2 months of pregnancy are characterized by ___
polyhydramnios
____ is characterized by an abnormal accumulation of ___ within the ventricular system. In most cases, hydrocephalus in the newborn is due to an obstruction of the ____
Hydrocephalus - CSF - aqueduct of Sylvius [aqueductal stenosis]
____ describes a cranial vault that is smallerthan normal. Because the size of the cranium depends on growth of the brain, the underlying defect is in brain development. Causation of the abnormality is varied; it may be genetic [autosomal recessive] or caused by prenatal insults, such as infection or exposure to drugs or other teratogens. lntellectual disability occurs in more than half the cases
Microcephaly
For example, the ___ may be partially or completely absent without much functional disturbance. Likewise, partial or complete absence of the cerebellum may result in only a slight disturbance of coordination
corpus callosum
On the other hand, cases of severe ____ may not be associated with morphologically detectable brain abnormalities
intellectual disability
The leading cause of intellectual disability is, however, ____
maternal alcohol abuse
____ are rare tumors involving chromaffin cells that result in excessive production and release of epinephrine and norepinephrine causing paroxysmal episodes of hypertension, increased heart rate, headaches, and other associated symptoms. 25% are familial and have been associated with mutations in the ___ that plays a role in neural crest cell migration
Pheochromocytomas - RET gene
____ results from a failure of parasympathetic ganglia to form in the wall of a part or all of the colon and rectum because the neural crest cells fail to migrate
Congenital megacolon [Hirschsprung disease]
Most familial cases of Hirschsprung disease are caused by mutations in the ___, which codes for a cell membrane ___
RETgene - tyrosine kinase receptor
The ligand for the receptor is ____ secreted by mesenchyme cells through which crest cells migrate
GLIAL CELL DERIVED NEUROTROPHIC GROWTH FACTOR
