Chapter 9 Flashcards
Morphogenesis
Process where tissues and organs assume form in fetal development
Cells undergo rapid differentiation, proliferation, and migration
Teratology
The study of malformations
Morphogenetic errors (10, list em)
Agenesis
Aplasia
Hypoplasia
Dysraphic anomalies
Involution failures
Division failure
Atresia
Dysplasia
Ectopic
Dystopia
Agenesis
Morphogenetic error
Complete absence of an organ, part of an organ, or tissues/cells within an organ
Aplasia
Morphogenetic error
Absence of a fully developed organ or tissue, but the structure was present at an early fetal stage
Hypoplasia
Morphogenetic error
Reduced size of an organ or tissue
Dyraphic anomalies
Morphogenetic error
Failure of a normal fusion of apposed structures
(Eg. spina bifida)
Involution failures
Morphogenetic error
Persistence of fetal structures that would normally regress
Division failure
Morphogenetic error
Incomplete cleavage of structure
(Webbed fingers)
Atresia
Morphogenetic error
Incomplete formation of lumen of a structure
(Esophageal atresia)
Dysplasia
Morphogenetic error
Abnormal organization of cells in a tissue
Ectopia
Morphogenetic error
Organ is in an anatomically abnormal location
Dystopia
Morphogenetic error
Failure of an organ to move into the usual position during development
Teratogens
Chemical, biological, or physical influences that disturb normal morphogenesis
Examples of teratogens (classes)
They are a class of toxin
Main classes
- radiation
- chemical substances
- infectious agents
Like other toxins, each chemical teratogens has a…
Specific mechanism of action
Difference between teratogens and a fetotoxin
Teratogen
- produced morphogenetic errors
Fetotoxin
- causes toxin effects like low birth weight and increases risk of premature delivery and death
Examples of chemical teratogens
Alcohol, cocaine
Tetracycline
Nicotine, tar
Teratogenic bacteria examples
Treponema palladium
Toxoplasma gondi
Viral is more common
Some examples of teratogenic viruses
Cytomegalovirus, herpes simplex, rubella, VZV
Anencephaly
Neural tube defect
- dysraphic defect (neural tube fails to close)
Leaves a brain which may be absent, incomplete, or exposed
Typically the cranial is absent or incomplete
Spina bifida
Neural tube defect
Can have range of severity
Exposure of the spinal cord due to improper development of the neural tube
Meningocele
Neural tube defect
Type of spina bifida
- sac of fluid protrudes out of baby’s back
Neural tube defects have been linked to:
Folic acid deficiency
Teratogenic effects of alcohol
Alcohol produces neurological effects, impaired growth, and in severe cases, FAS and facial deformities
Clinical signs of FAS
Abnormal facial features
- smooth upper lip
Small head
Short
Low BW
Poor coordination
Hyper
Attention difficulties
Bad memory
Thalidomide as a teratogen
Originally prescribed to pregnant women as a way to alleviate morning sickness
Quickly found highly toxic
- spontaneous abortions and limb malformation in babies
Now used as a anti neoplastic drug in adults
Phocomelia
Severely impaired limb development
Congenital syphilis
Can cause malformations of the skeletal system, lower extremities, teeth, eyes, ears
As well as anemia, jaundice, rash, hepatosplenomegaly
Inheritance of many single gene disorders fall into 4 classic Mendelian schemes:
Autosomal dominant
Autosomal recessive
X linked dominant
X linked recessive
Dominance occurs when where a:
Mutant allele in a heterozygote gives rise to phenotype of clinical manifestations of a disorder
Recessive disorders require;
Both copies of the mutated gene to be present
Homozygous for the mutant gene
Dominant vs recessive disorders
Both copies of the mutated gene to be present
Homozygous for the mutant gene
Autosomal genes
Genes not on sex chromosomes
Genes on the X chromosome are referred to as:
Why?
X linked or sex linked
There are very few Y linked disorders due to the small number of genes on a Y chromosome
If there is a recessive gene not eh X chromosome of a male, what happens and why?
The gene will be expressed
This is because the recessive gene will have no counterpart due to only 1 X chromosome
Pedigree charts can be used to:
Form analysis patterns of transmission of genes in families
Can discern Mendelian patterns and identify dominance of genes, recessivity, and X linkage
Autosomal dominant disorders are usually:
Heterozygous
Autosomal dominant patterns typically displays teh following traits: (4)
Affected person has an affected parent
Affected persons mating with normal persons have equal chance of producing affected offspring
Unaffected children born to affected parents will have unaffected children
Males and female have equal chance
Huntington disease
Autosomal dominant disease
Causes loss of motor control in adulthood, even though its congenital
Huntingtin protein (HTT) thought to be involved in cell signaling
Neurofibromatosis
Autosomal dominant condition found in two forms (NF1 and NF2)
NF1
Neurofibromatosis type 1
Leads to lesions at teh CNS and PNS nerve endings
- can be less or more severe
- can have neurofibromas (fibrous tumors at PNS nerve endings)
NF2
Neurofibromatosis type 2
Often affects auditory and vestibular systems with tumors
Polycystic kidney disease
Autosomal dominant
- delayed onset
- enlarged kidneys with cysts
- kidney dysfunction
- hematuria
Affects PKD1 and PKD2 genes
Marfan syndrome
Autosomal dominant disorder of connective tissue
- can include long and spindly limbs and digits
- pectus excavatum/carinatum
- scoliosis
- serious issues include aortic weakness
- linked to fibrillin gene on C15, which affects the formation of the elastic component of connective tissue
Autosomal dominant disorders (list, 4)
Huntington disease
Neurofibromatosis
Polycystic kidney disease
Marfan syndrome
Autosomal recessive
Facts
Theses mutations are widespread but often silent in most heterozygotes at the point of mutation
Heterozygotes contribute one copy of the mutation are genetic carriers 9able to pass the allele on but not have the condition)
Teh mutation is generally expressed if teh gene is homozygous, meaning teh maternal and paternal derived parts of the chromosome carry it
Typical autosomal recessive disorders have teh following features:
Mutant allele is masked by normal allele in a heterozygote individual
Only the homozygous genotype will show clinical signs
The trait appears in siblings, but not parents
Males and females equally affected
Both the parents of the affected child carry the recessive gene
Thalassemias
Most prevelant autosomal recessive disorders globally
Caused by mutation in hemoglobin
Homozygosity of one of these genes (two A/ two B) will lead to abnormal RBCs which will be destroyed when passing through the spleen.
This leads to anemia
Other manifestations include bone deformations in face, fatigue, pallour
Sickle cell disease
Autosomal recessive disorder
Mutation of hemoglobin gene causes protein to have abnormal structure in hypoxic conditions
Leads to deformation of RBCs which occlude in small vessels and spleen, leading to anemia
Why is sickle cell anemia and thelassemmias so prevalent in areas of malaria
Because their survival rate is higher
Tay-sachs disease
Autosomal recessive disorder
Lipid storage abnormality due to lysosomal dysfunction
- leads to neurological toxicity and maldevelopment
Usually kills kids before 4 due to brain degeneration
Cystic fibrosis
Autosomal recessive disorder
Presence of abnormally viscous mucus that is not easily cleared by the patient
Accumulation of mucus leads to severe respiratory problems (infections), as well as impaired digestion and absorption
Occurs on CFTR gene
Autosomal recessive disorders (4)
Thalassemias
Sickle cell disease
Tay-sachs disease
Cystic fibrosis
X linked disordered are:
Gene mutations carried on chromosome 23
Give rise to syndromes that are different between men and women
Appear in higher counts in men because X gene will always be expressed
X linked dominant disorders usually display the following patterns:
Affected males have normal sons and affected daughters
Heterozygous affected females have 50% change to produce affected kids
Disorders are more serious in men since they are hemizygous for affected genes
Compared to X linked recessive disorders, X linked dominant disorders are:
Uncommon
Fragile X syndrome
X linked dominant disorder
- features very long CGG repeats on X chromosome
- reduces protein needed for normal development of neural connections
Causes mild to moderate disability, low muscle tone, long face, large ears and balls
Manifestations include hyperactivity, autism, seizures
Often only diagnosable after puberty
Big ball syndrome
X linked recessive disorders typically display the following patterns
Males are affected more
Affected males cannot transmit gene to sons
Sons of female carries have 50% chance of being affected
Daughters of female carriers have 50% change of being a carrier
Duchenne disease
X linked recessive disorder
- passed from maternal side
- manifests as severe muscle wasting usually in early childhood
- use of arms/legs, ability to maintain spinal position are both lost
Delayed age of onset
Some disorders have been observed to only manifest later in life
- classic example is huntingtons
Gene penetrance
Refers to the probability that the gene is expressed
In other words, percentage of those known carrying an allele that will clinically manifest the disease
Disease can have high or low penetrance
Expressivity
Refers to the degree to which train expression differs between individuals
Often related to the type of mutation that affect protein formation
Genomic imprinting
Refers to the observation that genes will be expressed in a person differently depending upon which parent the gene came from
For example, time of onset of huntingtons will depend on if the allele for it was inherited from mom (42 avg age) or dad (33 avg age)
Polyploidy
Occurrence of multiple copies of the entire chromosome set
Usually results in death
Subtypes
- triploidy (3n=69 chromosomes)
- tetraploidy (4n=92)
Anueploidy
Numerical aberration resulting in cells in non multiples of 23 chromosomes
Trisomy
Refers to either fewer or more then the normal number of a specific chromosome
Result of improper segregation of a chromosome during meiosis where one gamete receives both sets of a chromosome (one has 24 the other has 22)
Monosomy
Over or under dose of an entire chromosome (most chromosomes)
Usually not compatible with survival
Most common aneuploid conditions
Down syndrome (trisomy 21)
And C23 conditions like klinefelter (XXY, XXXY, etc) and turner syndrome (X0)
Klinefelter syndrome
Most prevalent aneuploid condition (XXY)
- manifests in feminization of the male
(Poor beard growth, breast development, small balls, wide hips)
- usually only noticeable after puberty
Triple X syndrome in women
Not that big of a deal
Sometimes manifested in taller height, intellectual impairment or behavioural alterations
Monosomy X and turner syndrome
When girls are born with only one X chromosome, causes turner syndrome
- shorter height, loss of normal reproductive ability occurs (ovarian degeneration)
- physical features include webbed neck, lymphedema, skeletal and kidney defects
Without hormone therapy most will be infertile
Trisomy 21 and Down syndrome
3 copies of chromosome 21
- delayed childhood development, intellectual impairment, impaired immunity, elevated risk for conditions like leukemia and heart defects
- shorter height, low muscle tone, different facial appearance
Risk rises with age of pregnancy (sharp rise at 35)
Trisomy 13 and 18
13 - Patau syndrome
18 - Edward syndrome (twice as common, still not very common)
Those who survive are mentally impaired (very low survival rate past a year for both
Edward’s - kidney stuff, microcephaly
Abnormalities in chromosome structure
Deletion of a segment
Duplication of a segment
Inversion of a segment
Translocation of a segment to a non homologous chromosome
Loss of a segment of chromosome
Chromosomal deletion
Cri du chat syndrome
Deletion on c5 that results in microcephaly, severe intellectual impairment, hypotonia, facial deformation
