Congenital abnormalities
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due to developmental error during fetal development
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almost always detected at birth
Developmental processes are occur at a rapid rate therefore errors have devastating implications
Stem cells differentiate into their specialized cell types, move to area of organ or tissue placement then divide.
Errors in embryogenesis – if they occur at the particular organs critical period in development that organ will be severely development
Different structures devel @ different times
Organogensis – begins at day 15 post conception therefore this is the most vulnerable time for mutations.
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each organ has its own critical period within fetal development – different organs develop at different times
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The CNS has an extensive critical period therefore most congenital abnormalities will also affect the CNS
Tatatogens: Mutagenic agents
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drugs
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microbes
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vitamin,mineral or nutrient deficiency
Taratogens: – agents that affect the fetal development environment
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the maternal body
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the environment outside the maternal body
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Falitamide:a taratogen causing limb reduction defects
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Alcohol: causes Fetal alcohol Syndrome
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Deficiency: Vitamin, mineral or nutrients eg folic acid
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Viral infections: eg Rubella virus causing german measles
Fig. gestational development
Genetic Abnormalities
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Not always present at birth
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genetic code mutations
eg diabetes
autosomal dominant and recessive
Homozygous for a particular gene when identical alleles of the gene are present on both homologous chromosomes.
Heterozygous for a particular gene when two different alleles occupy the gene’s position on the homologous chromosomes.
Types of Chromosomes
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autosomal chromosomes 22 pairs
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sex chromosomes –1 pair, 2 chromosomes the X and Y
3 primary types of abnormalities
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Chromosomal Abnormalities
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reflects an atypical number of chromosomes or a structural abnormality in one or more chromosomes.
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Trisomy 21 – Downs Syndrome
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Single gene (monogenic) Chromosomal Abnormalities
2a. autosomal recessive
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25% chance of the individual being affected
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50% of individuals will be carriers for the gene
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25% of individuals will be unaffected
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Cystic Fibrosis
2b. autosomal dominant
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25% of individuals will be carriers for the gene
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50% chance of inheritance
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25% will be lethals (noncompatoible with life)
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Dwarfism
2c.X-linked recessive
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the mutated affected gene is linked to the X chromosome
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hemophilia
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Complex trait (polygenic and environmental) Chromosomal Abnormalities
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type 2 diabetes
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more than one gene is affected
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lifestyle (enviro factors)
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Chromosomal abnormalities
Numeric abnormalities:
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Aneuploidy – extra or missing Chromosome
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Trisomy – additional Chromosome to the pair eg trisomy 21
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Monosomy – only one chromosome, one missing from the pair (lethal)
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named for the Chromosome # involved
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Karyotype is the characteristic chromosome complement of a eukaryote species
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Trisomy 21
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Turners Syndrome
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female XO (1 in 3000 live births)
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Klinfelters syndrome
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male XXY (1 in 500)
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fig 7-11
Structural defects:
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Chromosomal deletion: The loss of a segment of the genetic material from a chromosome.
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Chromosomal Inversion: a chromosome rearrangement in which a segment of a chromosome is reversed end to end.
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Chromosome translocation: is a chromosome abnormalitycaused by rearrangement of parts between nonhomologous chromosomes.
Martin, Glenn and Porth, Carol, Mattson. 2009. Pathophysiology Concepts of Altered Health States. 8th ed. Lippincott Williams and Wilkins. Philadelphia