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
genetics of angelman syndrome?
error in genetic imprinting. 15q11.2 deletion. maternal derived
angelman syndrome is also called ?
happy puppet syndrome because the child is always laughing inappropriately
features of angelman syndrome?
- inappropriate laughter – happy-puppet syndrome
- developmental delay
- ataxia
- severe speech impairment
genetics of fragile X syndrome? pathogenesis
X linked dominant disorder due to a mutation in the FMR1 gene. this FMR1 genetic mutation is caused by unstable expansions of the trinucleotide sequence CGG. if the expansion is >200 repeats, it results in a complete loss of function of FMR1, and the classical phenotype. if the expansion is between 50-200 repeats, it results in an active FMR1 with a different and a milder phenotype
clinical features of fragile X syndrome?
- characteristic facial features: prominent mandible, large everted ears. long narrow face, prominent forehead,
- developmental delay and learning impairment
- post-pubertal macroorchidism and macrocephaly
- joint laxity
- mitral valve prolapse
- behaviour abnormalities: ADHD, ASD
phenotypical expression of fragile X between males and females?
50% of females affected with full mutation express phenotypical features, but milder than those expressed males
