genetics Flashcards
incidence of trisomy 21 with maternal age of 20?
1 in 1000 at 20 years
incidence of trisomy 21 with maternal age of 45?
1 in 20
overall risk of having fetus with trisomy 21?
1 in 650
antenatal screening for trisomy 21?
first trimester combined screening with non-invasive prenatal testing:
- maternal age
- serum markers: including b-hCG and PAPP-A
- ultrasound findings: nuchal translucency
definitive diagnosis of trisomy 21 in the antenatal period?
amniocentesis or chorionic villus sampling (CVS) for karyotyping
congenital features of trisomy 21?
1) craniofacial dysmorphology: round face, flat nasal bridge, epicanthic folds, brush field spots, protruding tongue, low set eats, short neck, flat occiput, and a third fontanelle
2) hypotonic
3) single palmar crease and toes sandal gap
4) congenital heart defect: atrioventricular septal defect in 40%
5) GI effects: duodenal atresia, hirchsprung disease
chronic features of trisomy 21?
- delayed motor milestones
learning - learning difficulties: IQ < 70
- hearing and visual impairments
- short stature
- predisposed to: leukemia, epilepsy, early-onset Alzheimer, hip dislocation, and Atlanta-axial instability
… is the most common inherited cause of learning difficulties, followed by fragile X syndrome
trisomy 21
antenatal findings of Turner syndrome?
streak ovaries
cystic hygroma
edema
clinical features of Turner syndrome?
- always short (absent SHOX gene) and infertile
- congenital heart disease: bicuspid aorta valve and co-arctation of the aorta
- webbed neck, widely space nipples, and broad shoulders
- delayed puberty: due to ovarian dysgenesis
- normal IQ
Management of turners syndrome?
- hormone replacement therapy to induce puberty
- growth hormone for height
- IVF for pregnancy
clinical features of Klinefelter syndrome?
- tall male
- gynecomastia and sparse facial hair
- small testicles
- most cases have a normal IQ but some experience psychological problems
5.predisposed to endocrine and psychiatric disorders
genetics of DiGeorge syndrome?
a disorder caused by chromosomal deletion at 22q11.2
another name for DiGeorge syndrome?
velcocardiofacial syndrome
characteristics features of Digeorge syndrome? CATCH-22
- cardiac anomaies: tetralogy of fallot
- abnormal facies: hypertelorism, antimongoloid slant
- thymic hypoplasia
- cleft life or palate
- hypocalcemia: from underdeveloped parathyroid gland
- 22q11.2 deletion
how may a neonate, infant, adolescent present with DiGeorge syndrome?
congenital abnormalities such as cleft lip/palate, cardiac anomalies
- neonate: congenital abnormalities (cleft, tetralogy of fallot)
- Later: hypocalcemic seizures, severe infections (thymic hypoplasia results in SCID), learning difficulties
- schizophrenia/ schizoaffective disorder presents in 25% of cases
definitive diagnosis of DiGeorge syndrome ?
- 22q11.2 deletion on microarray CGH
- > 3 weeks of hypocalcemia
- low T cell count
management of DiGeorge syndrome?
- surgical correction of any present defect
- calcium supplements
- vaccination (live vaccines are contraindicated
- consider thymic or bone marrow transplants
genetics of William syndrome?
deletion of 7q11
features of William syndrome?
dysmorphic features and mental retardation
overfriendliness
congenital heart disease: supravalvular aortic stenosis
hypertension and hypercalcemia
genetics of Prader- Willi syndrome ?
a genetic disorder caused by 15q11.2 deletion inherited from father (paternal genetic imprinting)
clinical features of Prader-Willi syndrome?
- hallmark: profound hypotonic neonate
- infant: poor suckling reflex and poor feeding
- Toddlers 1-6 years old; developmental delay, compulsive hyperplasia leading to obesity, short stature
diagnosis of Prader Willi syndrome?
DNA methylation analysis (due to implication of the genetic imprinting process