Congenital and Genetic abnormalities

 

Congenital abnormalities

 

1. due to developmental error during fetal development

2. 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.

 

• each organ has its own critical period within fetal development – different organs develop at different times

• The CNS has an extensive critical period therefore most congenital abnormalities will also affect the CNS

 

Tatatogens: Mutagenic agents

• drugs

• microbes

• vitamin,mineral or nutrient deficiency

 

Taratogens: – agents that affect the fetal development environment

• the maternal body

• the environment outside the maternal body

 

1. Falitamide:a taratogen causing limb reduction defects

2. Alcohol: causes Fetal alcohol Syndrome

3. Deficiency: Vitamin, mineral or nutrients eg folic acid

4. Viral infections: eg Rubella virus causing german measles

 

Fig. gestational development

 

Genetic Abnormalities

 

• Not always present at birth

• 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

1. autosomal chromosomes 22 pairs

2. sex chromosomes –1 pair, 2 chromosomes the X and Y

 

3 primary types of abnormalities

 

1. Chromosomal Abnormalities

• reflects an atypical number of chromosomes or a structural abnormality in one or more chromosomes.

• Trisomy 21 – Downs Syndrome

 

1. Single gene (monogenic) Chromosomal Abnormalities

2a. autosomal recessive

• 25% chance of the individual being affected

• 50% of individuals will be carriers for the gene

• 25% of individuals will be unaffected

• Cystic Fibrosis

 

2b. autosomal dominant

• 25% of individuals will be carriers for the gene

• 50% chance of inheritance

• 25% will be lethals (noncompatoible with life)

• Dwarfism

 

2c.X-linked recessive

• the mutated affected gene is linked to the X chromosome

• hemophilia

 

1. Complex trait (polygenic and environmental) Chromosomal Abnormalities

• type 2 diabetes

• more than one gene is affected

• lifestyle (enviro factors)

 

 

1. Chromosomal abnormalities

Numeric abnormalities:

 

• Aneuploidy – extra or missing Chromosome

• Trisomy – additional Chromosome to the pair eg trisomy 21

• Monosomy – only one chromosome, one missing from the pair (lethal)

• named for the Chromosome # involved

• Karyotype is the characteristic chromosome complement of a eukaryote species

   

1. Trisomy 21

2. Turners Syndrome

• female XO (1 in 3000 live births)

1. Klinfelters syndrome

• male XXY (1 in 500)

• fig 7-11

 

Structural defects:

1. Chromosomal deletion: The loss of a segment of the genetic material from a chromosome.

 

1. Chromosomal Inversion: a chromosome rearrangement in which a segment of a chromosome is reversed end to end.

2. 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