Disorders of Development
Congenital – Birth DefectsCongenital – Teratogenic Agents
Trisomy DisordersWilliam’s Syndrome
Autism
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.
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
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.
Critical Period Defect: Anencephaly (absence of brain)
•
Failure for the brain to grow beyond the rhombencephalon. Neonate failed to survive.
Critical Period Defect: Schizencephaly
Developmental 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.
Teratogens
Agents that cause congenital
malformations
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)
Genetic Conditions: Chromosomal Abnormalities
• Trisomy 21 (Down’s Syndrome)
• Trisomy of other chromosomes– Edward’s Syndrome (Trisomy 18)– Patau’s Syndrome (Trisomy 13)
Trisomy 21: Down’s Syndrome
Non-disjunction of the 21st Chromosome
Anatomical Dysmorphia & Risk (Increase with Maternal Age)
Just 1%-20% graphed here
How does Trisomy 21 happen?
First, normal development…
In normal development mitosis proceeds normally from the first cell division
In Down’s Syndrome, non-disjunction of the 21st chromosome can happen at the first cell division
Non-disjunction of the 21st chromosome cab occur after the first cell division resulting in a mosaic form of Down’s Syndrome
Faulty distribution can occur in the egg or sperm when the mother or father is a carrier.
Trisomy 18 – Edward’s Syndrome
Some Features of Edward’s Syndrome
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
Cardiovascular problems
Gastrointestinal and genitourinary problems
Life Span: death by 12-24 months (very few reach adulthood)
Incidence: 0.2/1000 births
Trisomy 13: Patau’s Syndrome
Features:0.1/1000 birthsSpina bifida & cleft palateCNS: underdevelopment of
frontal lobe (fails to divide) and corpus callosum
Profound Mental RetardationExtra fingers and toes, deafLife Span: 82% die in the
first month, 5-10% die in first year.
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
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
Genetic Abnormality of Chromosome 7:
21 genes missing
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.
Autism
A neurodegenerative disorder characterized by impairment in social interaction and communication.
Age of onset: typically between ages 2 and 4 (sometimes earlier)
Symptoms
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
Microglia Activation in Autism
(white matter of the cerebellum)
Microglial cells
Brain Areas Affected in Autism: Fusiform Face Area (FFA), Amygdala, Left Frontal Lobe, Left
Temporal Lobe, and Cerebellum
References for Photos (slides 5,6,9,11,16,18,19,22-25)
http://images.google.com/imgres?imgurl=http://www.hallym.or.kr/~kdcp/cytogenetics/cytogen-ds.files/c6_cleft_lip.jpg&imgrefurl=http://www.hallym.or.kr/~kdcp/cytogenetics/cytogen-ds.htm&h=483&w=316&sz=61&tbnid=9z1GFXy5kykJ:&tbnh=126&tbnw=82&hl=en&start=61&prev=/images%3Fq%3DWilliams%2BSyndrome%26start%3D60%26svnum%3D10%26hl%3Den%26lr%3D%26client%3Dfirefox-a%26rls%3Dorg.mozilla:en-US:official_s%26sa%3DN
http://images.google.com/imgres?imgurl=http://cas.bellarmine.edu/tietjen/HumanBioogy/Finished%2520Images/gen12.gif&imgrefurl=http://cas.bellarmine.edu/tietjen/HumanBioogy/bills_developmental_abnormalities.htm&h=383&w=400&sz=117&tbnid=KbFuC4QsI4sJ:&tbnh=114&tbnw=120&hl=en&start=3&prev=/images%3Fq%3DEdward%2527s%2BSyndrome%26svnum%3D10%26hl%3Den%26lr%3D%26client%3Dfirefox-a%26rls%3Dorg.mozilla:en-US:official_s%26sa%3DG
http://images.google.com/imgres?imgurl=http://www.cmu.edu/cmnews/extra/extra_art/Just_Fig1.jpg&imgrefurl=http://www.cmu.edu/cmnews/extra/extra_art/&h=421&w=150&sz=25&tbnid=0aXX65rnVysJ:&tbnh=122&tbnw=43&hl=en&start=189&prev=/images%3Fq%3Dautism%2Bbrain%26start%3D180%26svnum%3D10%26hl%3Den%26lr%3D%26client%3Dfirefox-a%26rls%3Dorg.mozilla:en-US:official%26sa%3DN
http://www.altcorp.com/DentalInformation/autismcytokines.htm
http://www.neuro.jhmi.edu/neuroimmunopath/Microglia%20pictures/5_lg.jpg
http://images.google.com/imgres?imgurl=http://www.fetalalcohol.com/images/face-thm.gif&imgrefurl=http://www.fetalalcohol.com/what-is-fase.htm&h=260&w=304&sz=16&tbnid=RpmOv4g5G04J:&tbnh=95&tbnw=112&hl=en&start=6&prev=/images%3Fq%3DFetal%2BAlcohol
%2BSyndrome%26svnum%3D10%26hl%3Den%26lr%3D%26client%3Dfirefox-a%26rls%3Dorg.mozilla:en-US:official_s%26sa%3DG http://images.google.com/imgres?imgurl=http://www.infobiogen.fr/services/chromcancer/IntroItems/Images/tri21FaceEng.gif&imgrefurl=http://www.infobiogen.fr/services/chromcancer/IntroItems/PolyTri21Eng.html&h=429&w=463&sz=50&tbnid=XGXbYU9uVcYJ:&tbnh=115&tbnw=125&hl=en&start=1&prev=/images%3Fq%3DTrisomy%2B21%2Bface%26svnum%3D10%26hl%3Den%26lr%3D%26client%3Dfirefox-a%26rls%3Dorg.mozilla:en-US:official_s%26sa%3DG