Developmental Abnormalities Mechanisms

Question 1

Developmental Diseases

Answer 1

Normal development is a complex process

Most developmental disease we recognize morphologically are due to abnormal embryogenesis

Congenital - Manifested at birth

Some deveolopmental diseases are manifested later in life due to abnormal postnatal development

Acquired - Occur after birth

Question 2

Developmental Disease:

Causes

Answer 2

• Two main categories of factors contribute to developmental diseases
  
  • Genetic Factors
  • Environmental Factors
• A combination of these factors influences the development of many developmental diseases
• The cause of approximately 65% of congenital developmental disease is never determined
  
  • of those whose cause is determined
    
    • 70% are genetic
    • 30% are environmental

Question 3

Genetic Factors

Answer 3

• Genetic factors can be placed into 3 major categories
  
  • chromosomal abnormalities
  • Single Gene Abnormalities
  • Multifactor Abnormalities

Question 4

Genetic Factors:

Chromosomal Abnormalities

Answer 4

• Most common abnormality associated with severe morphological defects
• Abnormalities are mainly due to changes in chromosome number or structure
  
  • change in number
    
    • monosomy:
      
      • the cell has one less chromosome
    • Trisomy:
      
      • The cell has one extra chromosome
  • Some chromosomal abberations can be transmitted through some, but not all cell lines during embryonic development
    
    • mosaicism
  • Changes in Chromosome structure
    
    • breakage can result in loss or rearrangement of chormosomes
      
      • can be deleted, inverted, or translocated
    • Most of these defects result in embryonic death, abortion, or stillbirth

Question 5

Genetic Factors:

Single Genes

Answer 5

This is a BIG DEAL

• Single gene abnromalities result in changes in a single protein
  
  • protein may be structurally altered or expression may be affected
• These are often manifested as a functional abnormality
• These are not commonly associated with severe morphological defects
• Major Categories of Genes affected
  
  • Structural Proteins
  • Receptor Proteins
  • Enzymes
  • Regulatory Proteins
• Inheritance can be autosomal or sex-linked
  
  • Autosomal
    
    • Dominant: appear in every generation with onset generally later in life
    • Recessive: may not appear in every generation with onset generally early in life
  • Sex-linked
    
    • Mainly X-linked recessive: Transmitted by asymptomatic females to some male offspring

Question 6

Genetic Factors:

Multifactorial

Answer 6

Disease due to two or more gene abnormalities usually along with some environmental factors

Multifactorial contributions are common with many normal traits, as well as both developmental and non-developmental diseases

Question 7

Syndactyly

Answer 7

Syn = one

Dactyly = digit

Condition in cattle characterized by fusion or nondivision of the two functional digits

“Mulefoot”

One of the most common deformities of the hand and feet in humans

Question 8

Bovine Syndactyly

Answer 8

• First reported in 1951
  
  • autosomal recessive trait
• Peak incidence occurred in 1970s
• Defect was mapped to Bovine chromosome 15 in 1996
  
  • conserved with human chormosome 11 and mouse chormosome 2
• Decet was mapped to 3.5Mb critical interval of the chromosome in 2006
• Defect due to a mutation in the LRP4 gene
  
  • a 2 base-pair substitution in exon 33
    
    • Glycine replaced cysteine
• Incidence of this condition has decreased due to progeny and genetic testing

Question 9

Environmental Factors

Answer 9

These include any external factor that can affect embryogenesis

Could be infection, chemical, nutrition

Question 10

Environmental Factors:

Infection

Answer 10

Fetal infection by a wide variety of agents can cause developmental anomalies

Bovine virus diarrhea virus

Feline panleukopenia virus

Bluetonge virus (cattle and sheep)

The age of fetal exposure has a critical impact on the nature of hte defect

Question 11

Environmental Factor:

Infection:

Bovine Virus Diarrhea Virus

Answer 11

Fetal infection has different effects at different ages of development

• Exposure before 100 days
  
  • fetal death
• Exposure between 100 -170 days
  
  • various anomalies including cerebellar, cerebral, and ocular lesions
• Exposure after 170 days
  
  • persistant infections and lympoid atrophy

Question 12

Environmental Factors:

Infection:

Bluetongue virus in sheep

Answer 12

Viral exposure during development of cerebral hemispheres damages developing neurons and results in ventricular/cerebral anomalies

• Exposure between 50-55 days
  
  • hydranencephaly
• Exposure at 75 days gestation
  
  • porencephaly

Question 13

Porencephaly

Answer 13

Question 14

Hydranencephaly

Answer 14

Question 15

Environmental Factors:

Chemical

Answer 15

• Maternal exposure to many different chemicals can cause fetal anomalies
• These are most common in grazing animals exposed to toxic plants
• Pharmacological agents and industrial chemicals can induce anomalies
• The nature of the defect is highly dependent on the time of exposure during gestation

Question 16

Environmental Factors:

Chemicals:

Veratrum californicum

Answer 16

Exposure in sheep

• Ingestion at 14 days gestration
  
  • cyclopia and severe craniofacial defects
• Ingestion at 29 days gestation
  
  • metacarpal and metatarsal shortening
• Ingestion at 31 days gestation
  
  • tracheal and laryngeal stenosis (shrinking)

Question 17

Cyclopia in Sheep

Answer 17

• The condition is a severe manifestation of Holoprosencephaly (HPE)
  
  • defect in the embryonic forebrain
  • disorder resulting form failure of the embryonic forebrain to subdivide properly
  • The morphology of HPE can range from a single upper incisor, to cyclopia and other severe anomalies
  • Causes include a wide variety of genetic and environmental agents

Question 18

Environmental Factors:

Nutrition

Answer 18

• Failure of accesss to proper nutrients can affect fetal development
• Uterine or placental abnormalites can affect nutrient transfer
• Nutritional deficiencies or toxicity can alter fetal development
  *

Question 19

Environmental Factors:

Chemicals:

Vitamin A deficiency

Answer 19

Results in interference with normal bone formation to cause anomalies including:

Microphthalmia

polydactyly

Arthrogryposis

Cleft palate

Thickening ofn the bones of the skull