genetics

Question 1

incidence of trisomy 21 with maternal age of 20?

Answer 1

1 in 1000 at 20 years

Question 2

incidence of trisomy 21 with maternal age of 45?

Answer 2

1 in 20

Question 3

overall risk of having fetus with trisomy 21?

Answer 3

1 in 650

Question 4

antenatal screening for trisomy 21?

Answer 4

first trimester combined screening with non-invasive prenatal testing:
- maternal age
- serum markers: including b-hCG and PAPP-A
- ultrasound findings: nuchal translucency

Question 5

definitive diagnosis of trisomy 21 in the antenatal period?

Answer 5

amniocentesis or chorionic villus sampling (CVS) for karyotyping

Question 6

congenital features of trisomy 21?

Answer 6

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

Question 7

chronic features of trisomy 21?

Answer 7

1. delayed motor milestones
   learning
2. learning difficulties: IQ < 70
3. hearing and visual impairments
4. short stature
5. predisposed to: leukemia, epilepsy, early-onset Alzheimer, hip dislocation, and Atlanta-axial instability

Question 8

… is the most common inherited cause of learning difficulties, followed by fragile X syndrome

Answer 8

trisomy 21

Question 9

antenatal findings of Turner syndrome?

Answer 9

streak ovaries
cystic hygroma
edema

Question 10

clinical features of Turner syndrome?

Answer 10

1. always short (absent SHOX gene) and infertile
2. congenital heart disease: bicuspid aorta valve and co-arctation of the aorta
3. webbed neck, widely space nipples, and broad shoulders
4. delayed puberty: due to ovarian dysgenesis
5. normal IQ

Question 11

Management of turners syndrome?

Answer 11

1. hormone replacement therapy to induce puberty
2. growth hormone for height
3. IVF for pregnancy

Question 12

clinical features of Klinefelter syndrome?

Answer 12

1. tall male
2. gynecomastia and sparse facial hair
3. small testicles
4. most cases have a normal IQ but some experience psychological problems
   5.predisposed to endocrine and psychiatric disorders

Question 13

genetics of DiGeorge syndrome?

Answer 13

a disorder caused by chromosomal deletion at 22q11.2

Question 14

another name for DiGeorge syndrome?

Answer 14

velcocardiofacial syndrome

Question 15

characteristics features of Digeorge syndrome? CATCH-22

Answer 15

1. cardiac anomaies: tetralogy of fallot
2. abnormal facies: hypertelorism, antimongoloid slant
3. thymic hypoplasia
4. cleft life or palate
5. hypocalcemia: from underdeveloped parathyroid gland
6. 22q11.2 deletion

Question 16

how may a neonate, infant, adolescent present with DiGeorge syndrome?

Answer 16

congenital abnormalities such as cleft lip/palate, cardiac anomalies

Question 17

1. neonate: congenital abnormalities (cleft, tetralogy of fallot)
2. Later: hypocalcemic seizures, severe infections (thymic hypoplasia results in SCID), learning difficulties
3. schizophrenia/ schizoaffective disorder presents in 25% of cases

Question 18

definitive diagnosis of DiGeorge syndrome ?

Answer 18

1. 22q11.2 deletion on microarray CGH
2. > 3 weeks of hypocalcemia
3. low T cell count

Question 19

management of DiGeorge syndrome?

Answer 19

1. surgical correction of any present defect
2. calcium supplements
3. vaccination (live vaccines are contraindicated
4. consider thymic or bone marrow transplants

Question 20

genetics of William syndrome?

Answer 20

deletion of 7q11

Question 21

features of William syndrome?

Answer 21

dysmorphic features and mental retardation
overfriendliness
congenital heart disease: supravalvular aortic stenosis
hypertension and hypercalcemia

Question 22

genetics of Prader- Willi syndrome ?

Answer 22

a genetic disorder caused by 15q11.2 deletion inherited from father (paternal genetic imprinting)

Question 23

clinical features of Prader-Willi syndrome?

Answer 23

1. hallmark: profound hypotonic neonate
2. infant: poor suckling reflex and poor feeding
3. Toddlers 1-6 years old; developmental delay, compulsive hyperplasia leading to obesity, short stature

Question 24

diagnosis of Prader Willi syndrome?

Answer 24

DNA methylation analysis (due to implication of the genetic imprinting process

Question 25

genetics of angelman syndrome?

Answer 25

error in genetic imprinting. 15q11.2 deletion. maternal derived

Question 26

angelman syndrome is also called ?

Answer 26

happy puppet syndrome because the child is always laughing inappropriately

Question 27

features of angelman syndrome?

Answer 27

1. inappropriate laughter – happy-puppet syndrome
2. developmental delay
3. ataxia
4. severe speech impairment

Question 28

genetics of fragile X syndrome? pathogenesis

Answer 28

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

Question 29

clinical features of fragile X syndrome?

Answer 29

1. characteristic facial features: prominent mandible, large everted ears. long narrow face, prominent forehead,
2. developmental delay and learning impairment
3. post-pubertal macroorchidism and macrocephaly
4. joint laxity
5. mitral valve prolapse
6. behaviour abnormalities: ADHD, ASD

Question 30

phenotypical expression of fragile X between males and females?

Answer 30

50% of females affected with full mutation express phenotypical features, but milder than those expressed males