Disorders of Development Congenital – Birth Defects Congenital – Teratogenic Agents Trisomy Disorders William’s Syndrome Autism

1
Disorders of DevelopmentCongenital Birth
DefectsCongenital Teratogenic AgentsTrisomy
DisordersWilliams Syndrome Autism
2

• Birth Defects occur during Critical Periods in
  Development
• 1. Defects during Zygote are aborted
• 2. Defects in the remaining prenatal period are
  irreversible
• 3. Critical Periods a time of rapid change in
  the development of the organism (i.e., system or
  structure) and if interrupted will result in
  permanent congenital abnormalities.

3

• Sensitive periods in development
• 1. Occur prenatally and less irreversible
• 2. Interference will disrupt growth may result
  in subtle dysfunctions
• 3. Continues into post-natal period
• Teratogens
• - Agents that cause congenital malformations in
  critical periods, and subtle alterations in the
  brain during sensitive periods

4
(No Transcript)
5
Critical Period Defect Cleft Palate

• Irreversible congenital abnormality affecting a
  critical period (palate development) during the
  embryonic and early fetal stages
• May affect pituitary growth as the palate and
  anterior pituitary are derived from the same
  embryonic tissue.

6
Critical Period Defect Anencephaly (absence of
brain)

Failure for the brain to grow beyond the
rhombencephalon. Neonate failed to survive.
7
Critical Period Defect Schizencephaly Development
al of the brain affected during the fetal period
(i.e., growth of the forebrain). Cells either
failed to migrate or ventricular region failed to
close.
8
Teratogens Agents that cause congenital
malformations
9
Fetal Alcohol Syndrome
Features Growth retardation, neurodevelopmental
abnormalities (fine motor skills, LD, behavior
disorders, and mental retardation in 50).
Facial dysmorphia during embryonic period (week
4-8), CNS problems during the fetal period
(migration problems, smaller dendrites, few
neurons in brain regions)
10
Genetic Conditions Chromosomal Abnormalities

• Trisomy 21 (Downs Syndrome)
• Trisomy of other chromosomes
• Edwards Syndrome (Trisomy 18)
• Pataus Syndrome (Trisomy 13)

11
Trisomy 21 Downs Syndrome
Non-disjunction of the 21st Chromosome
12
Anatomical Dysmorphia Risk (Increase with
Maternal Age)
Just 1-20 graphed here
13
How does Trisomy 21 happen? First, normal
development In normal development mitosis
proceeds normally from the first cell division
14
In Downs Syndrome, non-disjunction of the 21st
chromosome can happen at the first cell division
15
Non-disjunction of the 21st chromosome cab occur
after the first cell division resulting in a
mosaic form of Downs Syndrome
16
Faulty distribution can occur in the egg or
sperm when the mother or father is a carrier.
17
Trisomy 18 Edwards Syndrome
18
Some Features of Edwards Syndrome

• Cardiovascular problems
• Gastrointestinal and genitourinary problems
• Life Span death by 12-24 months (very few reach
  adulthood)
• Incidence 0.2/1000 births

• Facial microcephaly, low set malformed ears
• Skeletal webbed neck, overlapping of fingers and
  fixed flexion of fingers
• CNS severe mental retardation, neural tube
  defect, ocular abnormalities
• Respiratory apnea

19
Trisomy 13 Pataus Syndrome

• Features
• 0.1/1000 births
• Spina bifida cleft palate
• CNS underdevelopment of frontal lobe (fails to
  divide) and corpus callosum
• Profound Mental Retardation
• Extra fingers and toes, deaf
• Life Span 82 die in the first month, 5-10 die
  in first year.

20
Williams Syndrome Partial Deletion of the 7th
Chromosome

• Features
• 1 in 20,000 births
• Neurodevelopmental delays, cognitive deficits,
  LD, ADHD
• Overly friendly, social
• Extremely empathic
• Low muscle tone
• Extremely sensitive hearing

21
Brain Areas Affected Amygdala activates more for
threatening scenes and very little for
threatening faces. This accounts for absence of
anxiety in interpersonal interactions (no fear,
hence over friendliness). Also, abnormal activity
in frontal lobe and a disconnect with the
amygdala (except for medial-prefrontal which is
linked to empathy and the only structure still
connected to the amygdala)
Normal Control Williams Syndrome
Amygdala
22
Elastin protein, made only during the prenatal
period, is absent and causes vascular problems
during life the missing elastin gene is use to
identify the 21 missing genes in Williams
Syndrome.
Genetic Abnormality of Chromosome 7 21 genes
missing
23
Autism

• A neurodegenerative disorder characterized by
  impairment in social interaction and
  communication.
• Age of onset typically between ages 2 and 4
  (sometimes earlier)

24
Symptoms
25
Theories for Etiology and CNS Problems

• Genetic alterations
• Prenatal exposure to toxins and/or viruses
• Maternal and fetal immune interactions
• Vaccination with mercury base

• Amygdala less active and area is smaller
• Hippocampus is smaller
• Frontal areas (medial prefrontal region) less
  active
• Less activity in the superior temporal sulcus
  (involved in understanding others)
• Larger heavier brain suggests apoptosis failure

26
Microglia Activation in Autism (white matter of
the cerebellum)
Microglial cells
27
Brain Areas Affected in Autism Fusiform Face
Area (FFA), Amygdala, Left Frontal Lobe, Left
Temporal Lobe, and Cerebellum
28
References for Photos (slides 5,6,9,11,16,18,19,2
2-25)

• http//images.google.com/imgres?imgurlhttp//www.
  hallym.or.kr/kdcp/cytogenetics/cytogen-ds.files/c
  6_cleft_lip.jpgimgrefurlhttp//www.hallym.or.kr/
  kdcp/cytogenetics/cytogen-ds.htmh483w316sz6
  1tbnid9z1GFXy5kykJtbnh126tbnw82hlenstart
  61prev/images3Fq3DWilliams2BSyndrome26start
  3D6026svnum3D1026hl3Den26lr3D26client3Dfi
  refox-a26rls3Dorg.mozillaen-USofficial_s26sa
  3DN
• http//images.google.com/imgres?imgurlhttp//cas.
  bellarmine.edu/tietjen/HumanBioogy/Finished2520Im
  ages/gen12.gifimgrefurlhttp//cas.bellarmine.edu
  /tietjen/HumanBioogy/bills_developmental_abnormali
  ties.htmh383w400sz117tbnidKbFuC4QsI4sJtb
  nh114tbnw120hlenstart3prev/images3Fq3DE
  dward2527s2BSyndrome26svnum3D1026hl3Den26lr
  3D26client3Dfirefox-a26rls3Dorg.mozillaen-US
  official_s26sa3DG
• http//images.google.com/imgres?imgurlhttp//www.
  cmu.edu/cmnews/extra/extra_art/Just_Fig1.jpgimgre
  furlhttp//www.cmu.edu/cmnews/extra/extra_art/h
  421w150sz25tbnid0aXX65rnVysJtbnh122tbnw
  43hlenstart189prev/images3Fq3Dautism2Bbra
  in26start3D18026svnum3D1026hl3Den26lr3D26
  client3Dfirefox-a26rls3Dorg.mozillaen-USoffic
  ial26sa3DN
•  
• http//www.altcorp.com/DentalInformation/autismcyt
  okines.htm
•  
• http//www.neuro.jhmi.edu/neuroimmunopath/Microgli
  a20pictures/5_lg.jpg

http//images.google.com/imgres?imgurlhttp//www.
fetalalcohol.com/images/face-thm.gifimgrefurlhtt
p//www.fetalalcohol.com/what-is-fase.htmh260w
304sz16tbnidRpmOv4g5G04Jtbnh95tbnw112hl
enstart6prev/images3Fq3DFetal2BAlcohol2BSy
ndrome26svnum3D1026hl3Den26lr3D26client3Df
irefox-a26rls3Dorg.mozillaen-USofficial_s26sa
3DG   http//images.google.com/imgres?imgurlhtt
p//www.infobiogen.fr/services/chromcancer/IntroIt
ems/Images/tri21FaceEng.gifimgrefurlhttp//www.i
nfobiogen.fr/services/chromcancer/IntroItems/PolyT
ri21Eng.htmlh429w463sz50tbnidXGXbYU9uVcYJ
tbnh115tbnw125hlenstart1prev/images3Fq
3DTrisomy2B212Bface26svnum3D1026hl3Den26lr
3D26client3Dfirefox-a26rls3Dorg.mozillaen-US
official_s26sa3DG