Genetic and Developmental Disorders Flashcards
Egg + sperm =
zygote
Zygote cells divide to form
Morula
Morula develops into
Blastocyst
Three primordial germ layers
Ectoderm
Mesoderm
Endoderm
The critical stages of organogenesis are characterized by:
Extensive cell division, migration and interaction; and
Extreme sensitivity to external influences
Teratogen
Any agent that causes fetal abnormalities
Breakdown of causes of fetal abnormalities:
75% unknown 20% genetic diseases 2% chromosomal abnormalities 2% infection 1% chemical
Exogenous teratogens
Physical (X-rays, radiation, etc)
Chemicals
Fetal Alcohol Syndrome
Intrauterine growth development, affecting development of brain
Typically presents with small cranium and jaw, thin upper lip, reduced mental processes
TORCH
Toxoplasma, Other, Rubella, Cytomegalovirus, Herpes Simplex
Microbial teratogens
Congenital Rubella syndrome.
Microcephaly, micropthalmia, congenital heart defects
Inflammation of liver, lungs, lymphosplenomegaly
Teratogenic effect of Toxoplasmosis and cytomegalovirus
Brain abnormalities; small eyes with inflammation, cataracts and calcifications
Teratogenic effect of Herpes
skin lesions
Chromosomal abnormalities can be:
- Structural
- Numerical
- trisomy
- monosomy
More common in sex chromosomes than autosomes
Trisomy 21
Downs Syndrome
Translocation or trisomy of chromosome 21
Associated with mental retardation, facial and limb abnormalities, defects in internal organs, hematologic abnormalities.
Turner’s Syndrome
Monosomy X
Short stature, webbing of neck, normal female genitalia, except ovaries don’t develop normally.
Klinefelter’s Syndrome
XXY
Infertile males.
Atrophy of testes. Tall, effeminate, gynecomastia
Heterozygous
Possess one recessive and one dominant copy of the allele
Homozygous
Possess either two recessive or two dominant copies of the gene.
Marfan’s Syndrome
Autosomal dominant disorder primarily affecting connective tissue. Defect in gene that codes for fibrilin
1/10000
Causes skeletal, cardiovascular and occular changes
Elongated head, eye abnormalities, aortic aneurysm, floppy mitral valve, vertebral deformity, arachnodactyly
Familial Hypercholesterolemia
Autosomal dominant disorder primarily affecting cardiovascular system. Mutation in gene encoding LDL receptor.
LDL cholesterol removal less efficient –> deposition of lipids in arteries
1/500 people
Xanthomas
Lipid-rich yellow nodules, consist of macrophages that have phagocytize cholesterol
Cystic Fibrosis
Autosomal recessive disorder affecting gene that codes for chloride transport channel in cell membrane.
1/2500 neonates (1/25 estimated carrier)
Almost exclusively found in those with European heritage
Lack of NaCl in glandular secretions –> lack of H2) –> increased viscosity of secretions –> obstruction of organs
In pancreas –> malabsorption of nutrients
In bronchial mucosa –> abnormal respiration
Recurrent bacterial infection
Lysosomal Storage Diseases
Autosomal recessive disorders related to deficiency of enzymes involved in intermediary metabolism.
Metabolites that can’t get fully degraded, digested or incorporated get stored in lysosomes
Types of Lysosomal Storage Diseases
Lipodoses, glycogenoses, mucopolysaccharidoses, Tay-Sachs
Normally classified by type of pathway affected.
All characterized by accumulation of metabolites that cannot be processed
Tay-Sachs Disease
Lysosomal Storage Disease (autosomal recessive)
Defect in the function of hexosaminidase A –> accumulation of ganglioside in the brain
Gradual loss of brain function –> often death by age 5
Phenylketonuria
PKU
Autosomal recessive defect of protein metabolism.
Problem with enzyme that metabolizes phenylalanine (phenylalanine hyroxylase – PAH) into tyrosine.
Phenylalanine cannot be metabolized and so accumulates in blood and tissues.
Can be controlled with diagnosis at birth and special diet. Without special diet –> mental retardation
Hemophilia
X-linked recessive disease
- internally hemorrhage, joint deformity resulting from hemarthrosis
Two types: Hemophilia A -- defect of Coagulation Factor VIII -- 1/5000 boys -- mild to severe symptoms Hemophilia B -- defect of Coagulation Factor IX -- 1/20000 boys -- always severe
Muscular Dystrophy
X-linked recessive disease characterized by progressive muscle wasting
-inadequate or absent dystrophin
Duchenne (most severe), Beckers (less severe)
Fragile X Syndrome
X-linked recessive form of mental retardation
CGG triplet repeat
Currently 80% penetrance, but seems to get more severe with successive generations
1/1250 boys, 1/2500 females
Anencephaly
Multifactorial development defect in which the midline structures covering the brain do not fuse, and spinal/brain development is severely disturbed
Diabetes Mellitus
Disturbance of intermediate metabolism –> hyperglycemia
Multifactorial
Forms of prenatal diagnosis
Ultrasound
Chorionic villus biopsy (fetal cells)
Amniotic fluid analysis
Maternal blood analysis (AFP - alpha-fetoprotein; triple-screen marker test)
Prematurity
Born before 37th week, and weighing less than 2500g
Immaturity
Less than 1500 g and cannot survive outside NICU
Most important risk factor for prematurity
Premature rupture of amniotic membrane
Neonatal Respiratory Distress Syndrome
In premature infants, immature lungs may not have fully developed alveoli
- alveoli secrete surfactant to decrease surface tension and keep alveoli open
- in immature alveoli, lack of surfactant allows alveoli to collapse. Cells die
- necrotic cells and tissues coagulate and form a hyaline membrane, which further impedes gas exchange
- anoxia can cause death within 48 hours
Sudden Infant Death Syndrome
SIDS
1/500 births [1/2000 in Canada]
More common with poverty
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