Genetics Flashcards
What diseases are autosomal recessive
Cystic fibrosis
Tay Sachs
Phenylketonuria
Von Willebrands (2/3)
Alpha thal
Beta thal
Sickle cell
SMA
Gauchers
What diseases are autosomal dominant
Neurofibromatosis
Achondroplasia
Osteogenesis imperfecta
Huntington’s
Marfans
vWD (1/3)
What diseases are X-linked
Hemophilia
Fragile X
Duchenne’s muscular dystrophy
Red/green color blindness
G6PD deficiency
What diseases are multifactorial (genetic + environment)
Cleft lip/palette
Congenital heart disease
What is Turner’s syndrome
45 XO (gonadal disgenesis)
Characteristics: web neck, short, shield chest, cystic hygromas, cardiac and renal anomalies
Gyn implications:
- hypoestrogenic state
- no pubertal, breast devo or menarche
- Infertility (maybe in mosaics)
- increased risk of osteoporosis (HRT and Ca supplementation)
What are age specific risks of delivering infant with trisomy 21
Risk increases with age
How does trisomy 21 occur
Non-dysjunction–> failure of all chromatids to separate alone the metaphase plate during mitosis
Robertsonian translocation (increased risk of recurrence)–> a portion of one arm of a chromosome detaches and reattaches on another arm of a different chromosome
- balanced–> no chromosomal material lost
- unbalanced–> no material lost
How do you screen for aneuploidy
1st trimester screen
Triple screen
Quad screen
Integrated
Sequential
Contingent
Serum integrated
Cell free DNA
Nuchal translucency
What is the detection rate of Trisomy 13, 18 and 21 with cell free DNA
> 98%
How does cell free DNA work
Uses cell free fetal DNA from the plasma of maternal blood
What is amniocentesis vs chorionic villus sampling
Amniocentesis
- After 15 weeks
- Can assess AFP and NTD
CVS
- between 10-12 weeks
- Cannot assess NTD risk
- Samples tissue
What carrier screening should be done
All patients:
Cystic fibrosis
SMA
Hemoglobinopathies (CBC and electrophoresis or genetic testing)
What carrier testing is done for European/Jewish ancestry
Tay sachs
Cystic fibrosis
Canavan
Familial dysautonomia
How do you counsel for a pt wanting expanded carrier panel testing
Pre: may diagnosis a condition that is not an issue for fetus but can affect mother; may have abnormal results but it has unknown significance
Post: result based
What is fragile X syndrome
X linked recessive disease that occurs because of trinucleotide CGG repeats
- Permutation 50-200
- Mutation >200
Diagnostic testing done by PCR of souther blot
Most common cause of autism
Indications for screening
- known carrier
- intellectual disability or unknown etiology of fam hx of developmental delay
- unexplained ovarian insufficiency
- Autism
What is the occurrence/ reoccurrence risk of NTD
Gen pop: 0.3%
One affected child: 2-4%
Two affected kids: 10%
What are the recs for NTD prophylaxis
No hx: 0.4mg folate/day
Positive hx: 4mg folate/day
Typical regular diet: 0.2mg folate/day
Should give folic acid tablets for higher doses, as other vitamins in prenatal can be toxic in high levels
Normally start 1 mo prior to pregnancy and continue through 1st trimester; if high risk start 3mo prior to pregnancy and continue through 1st trimester
What are other causes of NTD not related to folate ingestion
- Valproic acid in first trimester
- High fetal glucose levels
- First trimester fever or prolonged elevated maternal temp (sauna use)
- Obesity
How do you assess for NTD
msAFP, fetal anatomy scan at 18-22 weeks
What is the difference between gastoschesis and omphalocele
Gastroschisis:
- 1:2500
- Right paraumbilical
- No membrane
- Abnormal embryo
- No associated genetic or structural anomalies
Omphalocele
- 1:5000
- Central (umbilical cord inserts at apex)
- Covering membrane
- Normal embryo at 9-11 weeks
- Liver herniation
- Associated with trisomies and other syndromes
