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