DEVELOPMENTAL DISEASES Flashcards
the conjunction of cardiac, limb, gut, and bladder abnormalities with a
neurologic disorder indicates the time at which the insult
takes place: cardiac abnormalities occur between the __________
fifth
and sixth week
Insult to the CNS timing:
meningomyelocele, before ____ days;
anencephaly, before 28 days;
cleft lip, before ______ days;
syndactyly, cyclopia, and holoprosencephaly, before ___
28
36
23 days
defects caused by chromosomal
abnormalities occur in approximately ______percent of live births, but such defects are found in more than ___
of spontaneous abortuses at 5 to 12 weeks gestational age
0.6
5 percent
_________ defined as hydrocephalus and
destruction or failure of development of parts of the cerebrum, is often associated with enlargement of the skull
Hydranencephaly,
causes of hydranencephaly
It can be caused by
cerebral infarction from intrauterine vascular occlusion
or by diseases such as toxoplasmosis and cytomegalovirus
(CMV) disease, which destroy parts of each cerebral
hemisphere.
This type of destruction
of the cerebral mantle in the embryonal period may
lead to the formation of huge brain defects with apposition
of ventricular and pial surfaces
(porencephaly)
result of a focal developmental defect in
the wall of the cerebral mantle
failure of evagination
schizencephaly
_____________, a
common congenital defect, may be associated with macrocephaly
and varying degrees of mental impairment, optic
defects, and seizures.
Agenesis of the corpus callosum
Imaging of agenesis of corpus callosum
“bat-wing” deformity of the ventricles
Agenesis of the corpus callosum is also part of the
_________and the ______________ and it has been noted, without explanation, in
some cases of nonketotic hyperglycinemia
Aicardi syndrome
Andermann
syndrome,
This term refers to a marked
enlargement of one cerebral hemisphere as a result of a
developmental abnormality.
megalencephaly
In megalencephaly, embryogenesis has been deranged at the stage
of ______
neuroblast formation
The growth
of the cranium is inhibited in a direction_______
to the involved suture(s), creating a compensatory
enlargement in other dimensions as allowed by the
patent sutures.
perpendicular
When only the sagittal suture i s involved, the head is
long and narrow _______ and the closed suture
projects, keel-like, in the midline
(scaphocephalic)
With premature closure
of the coronal suture, the head is excessively wide and
short _________
(brachycephalic) .
Approximately one-quarter of affected children with
craniostenoses will be found to have a single gene or
chromosomal abnormality, most commonly in the ____
FGFR3
gene.
When, for any reason, an infant lies with the head
turned constantly to one side (because of a shortened
sternomastoid muscle or hemianopia, for example), the
occiput on that side, over time, becomes flattened, as does
the opposite frontal bone
plagiocephaly, or wry head
During the
_________ postmitotic neurons that will ultimately
reside in the cortex arise in the ventricular zone adjacent
to the ventricles
first trimester,
the emergence
of two separate cerebral hemispheres may not
occur
holoprosenceph
One type of focal band-shaped subcortical
heterotopia is termed __________
“double cortex.
______________
refers to an excessive number of abnormally small gyri.
It is expressed by a syndrome of mental retardation, seizures,
delayed speech, and motor abnormalities
Polymicrogyria
These migrational disorders, particularly heterotopias, are
now being recognized more often by MRI and are found to
have a functional significance in epilepsy but also possibly
in such states as nonspecific ________ and _______
developmental delay, and
dyslexia
there is a failure of differentiation of intraand
intercortical and interhemispheral connections, the
most obvious one being _______
agenesis of the corpus callosum.
All that remains is a hemorrhagic
nubbin of nerve, glial, and connective tissue.
Brainstem, cerebellum, and spinal cord are present but
often, they too are malformed, as are the heart and other
organs (15 to 40 percent of cases).
Anencephaly
In Anencephaly,
mother ‘s serum levels of______and
________ are elevated–even more reliably
anticipated if they are elevated in the amniotic fluid.
alpha-fetoprotein
acetylcholinesterase
The causes of anencephaly are multiple and include
chromosomal abnormalities, maternal hyperthermia,
and, apparently, deficiencies of _____, ______, _______
folate, zinc, and copper
cortical convolutions
may be absent altogether and there is morphologic
evidence of several types of neuroblast deficiency
LISENCEPHALY
In some lissencephalic brains, there is
slight sulcation presenting as abnormally broad or narrow
convolutions, with thick, poorly laminated cortex;
these are called_________
pachygyrias or microgyrias
Alobar and lobar__________ are other examples
of sulcation defects with craniofacial abnormalities
in which development has gone awry in the fifth and
sixth weeks of gestation
holoprosencephalies
The ___________ represents a more
restricted form of migration and neural tube defect.
There is cerebellar vermian hypoplasia with or without
hydrocephalus and, in some cases, an added agenesis
of the corpus callosum with cerebral cortical dysgeneses
Dandy-Walker syndrome
Two
genes that modify microtubular function have been
identified : __________and “doublecortin” or___________
LIS 1
DCX
Large
chromosomal deletions that span LIS 1 cause _________, in which lissencephaly is associated
with distinctive facial abnormalities; small defects in
th same gene cause only lissencephaly
MillerDieker
syndrome
Lissencephaly
with cerebellar hypoplasia is caused by mutations
in the __________), the analogue of
the defective gene in reelin mice (which have a reeling
gait and abnormal cortical neuronal lamination)
human “reelin” gene (RELN
Defects irl the transcription factor ________are associated
with X-linked lissencephaly, agenesis of the corpus
callosum, and hypogonadism
ARX
_______ is caused by another gene defect, filamin
A gene on the X chromosome .
Periventricular nodular
heterotopia
In most of the above-described cerebral dysplasias, the
cranium and brain are small, but there is also a primary
form of hereditary microcephaly, called ____________ in which the head is astonishirlgly reduced in size (circumference
less than 45 em in adult life
microcephaly vera,
The
sulcal pattern is normal, and neuronal arrangements in
the cerebral cortex are normal as well. The defect appears
to be in the small number of neurons that are generated,
not in their migration.
radial microbrain
The general term ___________
is used to describe the several combinations of
craniostenotic and facial deformities and fusion of digits
acrocephalosyndactyly
- Acrocephalosyndactt;ly types I and II (typical and atypical ______________). Turribrachycephalic skull, syndactyly
of hands and feet (“mitten hands,” “sock feet”),
moderate to severe mental retardation. - Acrocephalosyndactyly III (Saethre-Chotzen syndrome) .
Various types of craniostenoses, _________
Transmission as an autosomal dominant trait. - Acrocephalosyndactyly IV (____________) .
Turribrachycephaly; broad, enlarged thumbs and
great toes; partially flexed elbows (radiohumeral or
radioulnar synostoses); mild and variable mental
retardation; autosomal dominant inheritance.
Apert syndrome
proximally fused and
shortened digits, moderate degree of mental retardation.
Pfeiffer syndrome
- Acrocephalopolysyndactyly V (________`).
Premature fusion of all cranial sutures with acrocephaly,
flat bridge of nose, medial canthi displaced
laterally, excess digits and syndactyly, subnormal
intelligence.
Carpenter syndrome
Variable degrees of craniosynostosis.
a genetic defect in one of the fibroblast growth factor receptors is responsible for about one-third of cases that are not associated with other deformities
Craniofacial dysostosis (Crouzon syndrome
Widely spaced eyes, broad
nasal root, cleft nose and premaxilla, V-shaped
frontal hairline, heterotypic anterior frontal fontanel
(midline cranial defect); mild to severe mental
retardation.
Median cleft facial syndrome (fron tonasal dysplasia;
hypertelorism of Greig)
All the patients are female;
they have pseudoclefts involving the mandible,
tongue, maxilla, and palate; hypertrophied buccal
frenula; hamartomas of tongue; sparse scalp hair;
subnormal intelligence in one-half of cases
Orofaciodigital syndrome.
Large head and frontal-occipital
bossing, underdeveloped facial bones, micrognathia,
unerupted and deformed teeth, dense and defective
long bones with shortened limbs, short and broad
terminal digits of fingers and toes, mental retardation
in one-quarter of the cases.
Pyknodysostosis.
Anophth!lmia with mental retardation. Associated genes are?
SOX2, RAX, RAX6
Also sex-linked recessive; some sight
may be present at birth; later, eyes become shrunken
and recessed (phthisis bulbi); some have short digits,
outbursts of anger, hallucinations, and possibly
regression of psychomotor function.
Norrie disease.
Autosomal recessive with absence of pigment of hair and
skin; small, cloudy, vascularized corneas and small
globes (microphthalmia); marked mental retardation;
athetotic movements of limbs
Oculocerebral syndrome with hypopigmentation
Chorioretinopathy,
retinal lacunae, staphyloma, coloboma of
optic nerve, microphthalmos, mental retardation,
infantile spasms and other forms of epilepsy, agenesis
of corpus callosum, and cortical heterotopias
Aicardi syndrome with ocular abnormality
In Aicardi syndrome:
The________of the third and lateral
ventricles on MR images and __________ and sleep spindles are diagnostic
“batwing” deformity
asynchronous burst suppression discharges
association with congenital muscular dystrophy.
Ocular lesions are a regular feature but
of variable type (retinal dysplasia, microphthalmia,
coloboma, cataracts, corneal opacities)
Lissencephaly of the Walker-Warburg type.
Visual loss from birth, moderate to severe mental
retardation, and microcephaly
Congenital tapetoretinal degeneration (Leber amaurosis
What differentiates Leber’s amaurosis and Lebers optic atrophy
Early onset of blindness
and absent electrical potentials on the electroretinogram
(ERG)
Diminished
visual acuity, small optic discs, absence of septum
pellucidum, and precocious puberty.
Septooptic dysplasia (de Morsier syndrome).
Type of Dwarfism
The cause is a homozygous or compound heterozygous
mutation in RAD3-realted protein, which
is also implicated in ataxia-telangectasia
Nanocephalic dwarfism (Seckel bird-headed dwarfism).
Possibly an autosomal dominant pattern of inheritance, with short stature of prenatal onset, craniofacial dysostosis, short arms, congenital hemihypertrophy (arm and leg on one side larger and longer),
Russell-Silver syndrome
Autosomal recessive
inheritance with microcephaly, broad nasal tip and
anteverted nares, wide-set eyes, epicanthal folds, ptosis,
small chin, low-set ears, enlarged alveolar maxillary
ridge, cutaneous syndactyly, hypospadias in
boys, short stature, subnormal neonatal activity, and
normal amino acids and serum immunoglobulins
Smith-Lemli-Opitz syndrome
Possible autosomal recessive
pattern of inheritance with microcephaly but no craniostenosis,
small and symmetrically receded chin,
glossoptosis (tongue falls back into pharynx), cleft
palate, flat bridge of nose, low-set ears, mental deficiency,
and congenital heart disease in half the cases
Pierre Robin syndrome
This is caused by deletions on
chromosome 17, in which there is learning disability,
severe behavioral problems (violence and self-injury),
hyperactivity, deafness, and ocular abnormalities
Smith-Magenis syndrome
an extensive vascular nevus located in the territory of the trigeminal nerve and sometimes in other parts of the body as well-causes permanent disfigurement and usually portends an associated and topographically underlying cerebral lesion
(Sturge-Weber syndrome)
This condition is transmitted
as an autosomal dominant trait and is characterized
by superficial pits in the palms and soles; multiple solid
or cystic tumors over the head, face, and neck appearing
in infancy or early childhood; mental retardation in
some cases; frontoparietal bossing; hypertelorism; and
kyphoscoliosis.
Basal-cell nevus syndrome.
Autosomal recessive with congenital ichthyosiform erythroderma, normal or thin scalp hair, sometimes defective dental enamel, pigmentary
degeneration of retinae, spastic legs, and mental retardation
Sjogren-Larsson syndrome.
there is a linear
nevus of one side of face and trunk, lipodermoids on
bulbar conjunctivae, vascularization of corneas, mental
retardation, focal seizures, and spike and slow waves in
the EEG. Genetics remain uncertain.
Linear sebaceous nevus syndrome
An eventration of brain tissue and its coverings
through an unfused midline defect in the skull is called an
________
encephalocele.
A failure of development of the midline portion
of the cerebellum referred to earlier, forms the basis of
the ________
Dandy-Walker syndrome
In_________, the cord
remains inside the canal and there is no external sac,
although a subcutaneous lipoma or a dimple or wisp of
hair on the overlying skin may mark the site of the lesion
spina bifida occulta
