Genetic and Congenital Disorder Flashcards
What are the 4 main stages of prenatal development?
- Pre-implantation embryonic stage.
- Germ layer formation.
- Early organogenesis.
- Definite organogenesis.
What is a congenital defect?
condition someone is born with.
What are the different types of congenital defects and what are the % they make up?
75% - is unknown causes. 20% - genetic diseases. 2% - chromosomal abnormalities. 2% - infections. 1% - chemicals.
What is a teratogen?
Environmental agent that interrupts the normal development of an organism
What are the three classifications of exogenous teratogens?
1) Physical teratogen
2) Chemical teratogen
3) Microbial teratogen
Give 3 examples of a physical teratogen?
1) x-ray
2) corpuscular radiation(alpha, beta, gamma rays)
3) A bomb.
What type of teratogen is thalidomide and what does it cause?
It is a chemical teratogen that lead to babies being born with phocomelia (flipper-like arms or legs).
What was thalidomide prescribed for?
Preventing morning sickness.
What type of teratogen would viruses, bactria, protozoal parasites be?
Microbial teratogens.
What is FASD’s?
Fetal alcohol spectrum disorders.
What are some symptoms of FASD’s?
1) Small for gestational age
2) Small eye openings
3) Poor coordination
4) Hyperactive behavior
5) Learning disabilities
6) Developmental disabilities (speech and language delays)
7) Low IQ
8) Poor reasoning and judgement skills
9) Sleep and sucking disturbances in infancy.
What is TORCH(ES) syndrome?
a medical acronym for a set of perinatal infections (i.e. infections that are passed from a pregnant woman to her fetus).
When should we test for TORCH(ES) syndrome?
Early in pregnancy.
What will the T in Torches syndrome stand for and how do we get it?
Toxoplasma we get it from cat shit so stay away from Julie.
What will the O in TORCHES syndrome stand for?
Others that are less common like Epstein-Barr virus, Varicella virus, Listeria monocytogenes, leptospira.
What will the R in TORCHES syndrome stand for?
Rubella.
What will the C in TORCHES syndrome stand for?
Cytomegalovirus (CMV).
What will the H in TORCHES syndrome stand for?
Herpesvirus.
What will the (ES) in TORCH(ES) syndrome stand for?
Syphylis.
What does rubella cause?
1) Small (microcephaly)/strucuraly abnormal brain
2) Heart defects.
What will Toxoplasma cause?
1) Microcalcification of basal ganglia and dilation of lateral ventricles (hydrocephalus)
2) CNS defects.
What will cytomegalovirus (CMV) cause?
The same as Toxoplasma.
What will herpesvirus affect?
1) CNS defects
2) Skin lesions.
What are 2 types of chromosomal anomalies?
Structural and numerical anomalies
What is Aneuploidy?
Loss or gain of chromosomes.
What are 2 types of aneuploidy?
Hyperdiploidy- 46+1 or 46+2.
Hypodiploidy- 46-1 or 46-2.
What is monosomy?
Missing one chromosome
What is Trisomy?
Gaining an extra chromosome (3 of one chromosome)
What is the most common risk factor for Down syndrome?
Paternal age increases risk of having a baby born with down syndrome
What disorder is associated with Down syndrome?
Trisomy 21 (D= drinking age 21)
What disorder is associated with Edward’s syndrome?
Trisomy 18 (E = election age 18)
What disorder is associated with Patau’s syndrome?
Trisomy 13 (P = puberty age 13)
Of the 3 disorders Down, Edward’s and Patau’s, which one is most common?
Down Syndrome
What happens to a baby’s hands with down syndrome?
Simian crease.
Down syndrome or trisomy 21 leads to what mental issues?
Most commonly leads to mental retardation
How will down syndrome affect the head?
Flat facial profile and epicanthic folds
How will down syndrome affect the heart?
Congenital heart defects like septum primum due to endocardial cushion defects.
How will down syndrome affect the limbs and feet?
Hypotonia
A gap between first 2 toes.
What is the life expectancy with edwards sydnrome aka trisomy 18?
less than 1 year.
What will edwards syndrome cause?
Severe mental retardation.
How will edwards syndrome affect the head?
1) Prominent occiput
2) micrognathia (small jaw)
3) low set ears.
How will Down syndrome affect the umbilicus and intestines?
Causes umbilical hernia and intestinal stenosis
What is the incidence of down syndrome?
1 in 700 births
How will edwards syndrome affect the heart?
Congenital heart defects will be present.
How will edwards syndrome affect the hands and feet?
Hands- Clenched hands
Feet- Rocker-bottom feet.
What is the life expectancy with down syndrome?
45-50 years old
What is the incidence of Edward’s syndrome?
1 in every 8000 births
What some limb changes with Edward’s symptoms
Limited hip abduction
Rocker bottom feet
What is the incidence of Edward’s syndrome?
1 in 8000
What are some neurological issues with patau symptoms?
Microcephaly and mental retardation
What are some head changes with patau symptoms?
Cleft lip and palate
Microphthalmia
What are some limb issues with patau symptoms?
1) Polydactylyl
2) Focker -bottom feel
What is the incidence of Patau syndrome?
1 in 15000
What is the life expectancy of Down syndrome?
45-50
What is the life expectancy of Edwards syndrome?
<1 year
What is the life expectancy of Patau syndrome?
<1 year
In which disorder(s), (Downs, Edwards, Patau) does mental retardation occur?
Yes, severe in Edwards and Patau
and the most common cause is Down Syndrome
What are some other disease risks for Down Syndrome?
ALL, Alzheimer’s >age 35
What are two disorders that are caused by abnormalities of sex chromosomes?
1) Turner syndrome
2) Klinefelter syndrome
Who can get turner’s syndrome and who can get Klinefelter’s syndrome?
They are abnormalities of sex chromosomes so only females can get Turners and Only males can get Klinefelter’s syndrome.
Pathogenesis of sex chromosome abnormalities are due to what?
Nondisjunction.
What is nondisjunction?
Failure of paired chromosome to separate.
How common is Turners syndrome?
1 in every 3,000 female births.
What are the symptoms of Turners syndrome? (It’s super long, sorry)
1) Short stature
2) heart- shaped face
3) low posterior hairline
4) webbing of neck
5) heart disease and coarctation of aorta
6) broad chest and widely spaced nipples
7) pigmented nevi (moles)
8) cubitus valgus(elbows turned in)
9) streak ovaries, hypoplastic uterus, amenorrhea
10) peripheral lymphedema at birth.
Are Turner’s considered male or female?
Female presentation
What symptoms will Klinefelter’s syndrome present with?
1) Tall long arms and legs
2) lack of beard body hair and pubic hair
3) gynecomastia
4) female like hips
5) testicular atrophy.
Is Klinefelter syndrome considered male or female?
Male presentation (based on penis presentation)
What is mendelian inheritance?
a set of primary principles relating to the transmission of hereditary characteristics from parent organisms to their offspring
What is heterozygotes and homozygotes?
Hetero - a particular gene pair will be different. Homo - the gene pair will be the same.
What are alleles?
Genes expressed in duplicate
What is the difference between autosomal dominant and autosomal recessive?
1) Recessive- a genetic condition that only appears in people that have both pairs of an autosomal(a non sex chromosome) gene.
2) Dominant- A genetic condition that appears in people that have 1 normal gene and 1 autosomal gene.
What is mitochondrial inheritance?
The inheritance of a trait encoded in the mitochondrial genome
With an autosomal dominant inheritance will the trait be apparent in heterozygotes?
yes.
In many cases when will mendelian inheritance present clinically?
After puberty.
What is critical in diagnosing a mendelian inheritance?
Family history.
What % will an affected heterozygote (autosomal dominant) have of transmitting the gene to offspring?
50%.
What % will an affected homozygote (autosomal dominant) have of transmitting the gene to offspring?
100%.
What % of children from parents who are both heterozygote (autosomal dominant). will be affected?
1) 25% will be homozygote.
2) 50% will be heterozygote,
3) 25% will be uneffected.
What is an autosomal dominant disease that affectes connective Tissue?
Marfan’s Syndrome
What is the clinical presentation of someone with Marfan’s syndrome?
1) Elongated hands
2) eye abnormalities
3) aortic aneurysm
4) floppy mitral valve
5) vertebral deformity
6) Long fingers (arachnodactyly)
How is Marfan’s syndrome inherited?
It is an autosomal dominant inheritance.
Marfan’s syndrome is a molecular defect of what?
mutation in the gene encoding the glycoprotein Fibrillin-1 (FBN1).
What is FBN1 involved in?
Main componenet of microfibrils and helps anchor cells to the ECM therefore causes connective tissue anomalies when absent
With marfan’s syndrome what are the principle structures that are defective?
Cardiovascular, musculoskeletal, ocular.
Besides the CV, MS and ocular areas, what else is effected by marfan’s syndrome?
Pulmonary and CNS.
Marfan’s syndrome is typically recognized by what?
Long limbs, aortic root dilation and dislocated lenses.
What happens with teenagers who have marfan’s syndrome?
kyphoscoliosis, pectus excavatum, genu recurvatum (knee has > 5 degree extension)
Achondroplastic dwarfism is what?
An autosomal dominant inherited bone disease.
Which is the most common type of dwarfism and what are the signs and symptoms?
Achondroplastic dwarfism (AKA Jim Dietrich Disorder) is the most common and it presents with:
1) Bulky forehead
2) saddle nose
3) lumbar lordosis
4) bowlegs.
What is the defective gene product that causes achondroplastic Dwarfism?
Fibroblast growth factor (FGF) receptor 3
What kind of disorder is Osteogenesis imperfecta ?
A hereditary collagen disorder
What clinical presentation does he collagen disorder of osteogenesis imperfecta present with?
1) abnormal fragility of bone
2) hearing loss, blue sclerae (seen with all collagen disorders)
3) dentinogenesis imperfecta
4) joint hypermobility.
How many types of osteogenesis imperfecta are there?
I-IV.
What types of osteogenesis imperfecta are caused by autosomal dominant inheritance and what cause the other types?
1) I and IV are autosomal dominant.
2) II and III are autosomal recessive.
How common is Hearing loss with osteogenesis imperfecta?
50-65%.
Of the 4 types of osteogenesis imperfecta rank them from mildest to most severe?
I-mildest < IV- intermediate in severity < III- most severe nonlethal form < II- most severe and lethal.
What clinical presentations are found with Type I osteogenesis imperfecta?
1) Blue sclera (d/t a deficiency in CT allowing underlying vessels to show through)
2) joint hypermobility leading to musculoskeletal pain
3) recurrent fractures in childhood are possible.
What clinical presentations are found with Type II osteogenesis imperfecta?
1) Blue sclera
2) shortened extremities due to multiple congenital fractures
3) skull is soft and feels like a bag of bones
4) Trauma during delivery may cause intracranial hemorrhage and stillbirths.
What clinical presentations are found with Type III osteogenesis imperfecta?
1) Short stature
2) spinal curvature and multiple
3) recurrent fractures
4) Macrocephaly with triagular facies
5) pectal deformities are common
6) hearing loss is possible
What clinical presentations are found with Type IV osteogenesis imperfecta?
1) Bones fracture easy in childhood before adolescence
2) Sclera normal color
3) moderate-short height.
What type of Osteogenesis imperfecta may benefit from treatment?
Type IV.
What is the survival rate like with osteogenesis imperfecta type IV?
survival rate is high.
With osteogenesis imperfecta which adult arm bones were defective in the x-ray he showed us?
Radius and ulna.
Blue sclera is associated with osteogenesis why?
Blue sclera is associated with connective tissue disorders and osteogenesis imperfecta is a collagen disorder.
Blue disoloration of the sclera happens when?
thinning of the sclera allows the underlying choroid to become visible.
What is elevated with familial hypercholesterolemia?
LDL.
Why will LDL be elevated with familial hypercholesterolemia?
Defective or absent LDL receptor.
What will cholesterol levels of heterozygote and homozygote familial hypercholesterolemia patients have?
1) Hetero- 300mg/dl.
2) Homo-700+ mg/dl.
Homozygotes with familial hypercholesterolemia develop what in early life?
Tendon xanthomas (tumor of lipid foam cells) classically seen in the achilles tendon.
What may develop with homozygotes with familial hypercholesterolemia by age 20?
MI.
What is the Liver’s role with LDL?
It is involved with synthesis and clearance.
There are 5 different classes of LDL receptor mutations and all of them are what?
Heterogeneous at the DNA level.
What should be taken to help with familial hypercholesterolemia and what are its 2 names?
Nicotinic acid aka Vitamin B3.
What effects will nicotinic acid and Vitamin B3 have on hypercholesterolemia?
Increases HDL and lowers TG and LDL.
What are the adverse effects of nicotinic acid (vitamin B3)?
1) Flushing
2) impaired glucose tolerance
3) increased uric acid.
What can be given with nicotinic acid to help with adverse effects?
Aspirin and given with food.
What type of diet can help lower cholesterol and how?
High fiber by binding to cholesterol before it can be reabsorbed in the liver.
What type of drugs are given to help lower cholesterol?
Statins.
What is PKD?
Polycystic kidney disease it is an autosomal dominant or recessive disease that affects the kidney.
What are the 2 forms of PKD and what causes them?
Adult- autosomal dominant.
Juvenile- autosomal recessive.
How common is the adult form or Autosomal dominant PKD?
1/1000 people.
Autosomal dominant PKD accounts for what % of patients with end-stage renal disease requiring replacement therapy?
5-10%.
Clinical manifestations of PKD happen when?
Rare before adulthood, but essentially all patients by 80 years of age or older.
How common is autosomal recessive PKD or the child form?
1/10,000 people.
PKD is associated with what?
Polycystic liver disease, berry aneurysms mitral valve prolapse.
What are berry aneurysms?
A small saccular aneurysm of a cerebral artery that resembles a berry.
86-96% of ADPKD (autosomal dominant PKD) cases are caused by what?
mutations in the PKD1 gene on chromosome 16.
What will the PKD1 gene on chromosome 16 code for?
Polycystin 1 protein.