Genetic and Developmental Diseases Flashcards
4 main stages in prenatal development
- Preimplantation embryonic stage (first cleavage to blastocyst)
- Germ layer formation (embryonic stage)
- Early organogenesis (organ primordia formation)
- Definite organogenesis (anatomical and functional maturation of organs)
Organogenesis
The production and development of the organs
Gamete
A mature reproductive cell (ovum or sperm) with the haploid chromosome number
Zygote
A fertilized ovum
What comes from the
- Ectoderm
- Mesoderm
- Endoderm
- Skin and nervous system
- Muscle, bone, kidneys, heart, vasculature
- Cells lining the gut cavity, the airways of the respiratory system and other similar structures
Early organogenesis
Marked by organ primordia formation
Definite organogenesis
Anatomical and functional maturation of organs
When neural tube defects can occur
Weeks 4-8
3 types of exogenous teratogens and some examples
- Physical (x-rays, corpuscular radiation)
- Chemical (industrial chemicals, drugs, alcohol)
- Microbial (viruses, bacteria, parasites)
Clinical symptoms of fetal alcohol syndrome
Recessed jaw Thin upper lip Palpebral abnormalities Development of internal organs may be impaired Mental development is affected Lower than normal IQ Psychosocial behaviour may be hindered
TORCH syndrome
Toxoplasma (Others)* - EBV, Listeria, Leptospira Rubella Cytomegalovirus Herpes virus
Effects of TORCH syndrome
Brain most often affected: microcephaly, mental retardation, neurological symptoms
Eyes: small, inflammation of inside layers, lens clouding
Heart: developmental defect
Liver/lung: inflammation, reactive enlargement of lymph nodes and spleen
Skin lesions: petechial hemorrhages and vesicles (post herpes)
Congenital Rubella Syndrome
Now prevented by materal immunization
Microcephaly, microphthalmia, congenital heart disease
What is a chromosome made up of?
1/3 each of DNA, RNA, and protein
Aneuploidy
Any chromosome number that is not an exact multiple of the haploid number (23)
Hyperdiploidy vs hypodiploidy
Hyper: 2n+
Hypo: 2n-
Trisomy 21
3 copies of chromosome 21 from non-disjunction during meiosis 1
Clinical features of down’s syndrome
Mental retardation Unique facial features Eye abnormalities Gaping mouth and large tongue Heart disease Intestinal defects Hand abnormalities Abnormalities of toes
Which gene controls male development?
SRY
Turner’s syndrome
Partial or complete absence of one X chromosome
Turner’s syndrome clinical features
Short stature Heart shaped face Webbing of neck Heart disease Broad chest Cubitus valgus Streak ovaries, hypoplastic uterus, amenorrhea (infertile)
Klinefelter Syndrome
Describes a group of chromosomal disorders in which there is at least one extra X chromosome in a male karyotype
47,XXY most common
Klinefelter Syndrome Clinical features
Tall, long arms and legs Lack of beard, body and pubic hair Gynecomastia (breasts) Female-like hips Testicular atrophy, infertility
WAGR syndrome
11p12-p14 deletions
Wilms tumor of the kindey, Aniridia (no iris), Genital malformation, mental Retardation
Results in loss of several important genes including WT1 (TSG)
Balanced reciprocal translocations
No loss or gain of clinically relevant genetic information
Positon change and no phenotype consequences
Reproductive consequences because offspring can inherit unbalanced form of the translocation
Alleles
Genes located on the autosomes are all expressed in duplicate (one on each homologous chromosome)
Autosomal Dominant Disorders
Apparent in heterozygotes
Affected hetero has 50% chance of passing it on
Expressed in every generation
Unaffected offspring do not transmit the trait
Marfan’s Syndrome
Autosomal Dominant
Clinically: elongated head, eye abnormalities, aortic aneurysm with dissection and exsanguniation, floppy mitral valve, vertebral deformity, long fingers
1 in 5000
Due to a structural defect in fibrillin
CT or tendon gets loose and cannot support body structures
Familial Hypercholesterolemia
Autosomal Dominant
1 in 500
Mutation in LDL receptor - so cholesterol is not getting removed from blood properly and you get deposits
Get atherosclerosis and coronary artery disease
Can be managed with a strict low fat diet and statin
Autosomal Recessive Disorders
Gene effect apparent only in homozygotes (one copy from each parent, who are usually asymptomatic carriers)
More common than autosomal dominant
Incidence of disease is lower because heterozygotes aren’t effected
Cystic fibrosis
Autosomal recessive (1 in 500, carrier 1 in 25)
Mutation in CFTR protein (critical for Cl- across cell membrane)
Effects all the glandular secretions of exocrine glands (systemic disease - become more viscous)
Problems in pancreas, fetal intestine, and bronchi
Definitions
- Meconium ileus
- Meconium peritonitis
Because of CF
- Ileus obstruction due to dehydrated contents of intestine
- Intestinal rupture and dissipation of intestinal contents throughout the abdominal cavity
Phenylketonuria
Autosomal recessive
Deficiency in phenylalanine hydroxylase (metabolizes phenylalanine to tyrosine)
Results in accumulation of phenylpyruvic acid that can cause neurological defects (slow and progressive but irreversible mental retardation)
Treat with a strict diet absent of phenylalanine
Tay-Sachs Disease
Autosomal recessive
Lysosomal storage disease
Defect in the function of hexosaminidase A
Results in the accumulation of GM2 gangliosides
Cells appear lipid filled, swollen, and vacuolated
Effects the brain and eyes, death by 3-5 years old
X linked Recessive Disorders
Usually only evident in males
Transmitted from an asymptomatic carrier mother
Hemophilia
Type A (factor 8) and B (factor 9)
Factor A deficiency more common than B because gene is much larger for A
50% have inherited form, other half is spontaneous
Multisystemic effects
Fragile X Syndrome
Fragility of X chromosome CGG triple nucleotide repeat Mental retardation Most common mental retardation in males 1 in 1250
Chorionic villus biopsy
At 10-14 weeks
Removal of a small amount of CV tissue which gives rise to placental tissue (98% of the time its reflective of the DNA of the fetus)
Has some risk for miscarriage
Prematurity vs Immaturity
Pre: birth before 30 weeks, weight less than 2500 g
Im: weight less than 1500 g
Neonatal Respiratory Distress Syndrome
Immature pneumocytes type 2 Surfactant deficiency Atelectasis, alveolar, endothelial injury of lungs Hypoxia-hyaline membrane Cerebral intraventricular hemorrhage
Sudden Infant Death Syndrome
Sudden unexpected death in infants older than 2 months and less than 9 months
Cause not known
Maternal risk factors (young, low socioeconomic status, drug users, etc)
Infant risk factors (premature, previous GI disease)
Most common cause of death in infants beyond immediate neonatal period
Autopsy shows lack of oxygen
