Down Syndrome

Question 1

What is Down Syndrome?

Answer 1

A genetic disorder caused by the presence of an extra 21st chromosome.

Question 2

Most striking feature in the neonate with DS?

Answer 2

Hypotonia

Question 3

Why Alzheimer disease (AD) is common in adults with DS?

Answer 3

Gene which codes for the amyloid protein which appears to cause AD is located in Chromosome 21.

Question 4

Chromosomal abnormalities of DS?

Answer 4

Trisomy 21 - 95%
Mosaicism - 2%
Unbalanced Robertsonian translocation - 3%

Question 5

Chromosomal findings in Mosaic DS?

Answer 5

e.g. 46,XX,/47,XX,+21

Question 6

Chromosomal findings in Trisomy 21?

Answer 6

e.g. 47,XY,+21

Question 7

Chromosomal findings in Unbalanced Robertsonian translocation?

Answer 7

e.g. 46XX,-15,+(15q21q)

Question 8

DS is the most common cause genetic cause of severe learning difficulties, True or False?

Answer 8

True

Question 9

If not diagnosed antenatally, DS is usually suspected at birth by what findings?

Answer 9

facial appearance

Question 10

Maternal screening tests to identify an increased risk of DS in the fetus?

Answer 10

Biochemical markers - triple test: AFP, unconjugated estriol, hCG plus inhibin-A (quadruple test) @ 15-20 weeks AOG and Nuchal thickening on ultrasound.

Question 11

White or grey spots in the periphery of the iris?

Answer 11

Brushfield spots

Question 12

in DS the fifth digit curves toward the fourth digit due to midphalanx dysplasia?

Answer 12

Clinodactyly

Question 13

Excessive shortening of hand and foot tubular bones resulting in a boxlike appearance?

Answer 13

Brachydactyly

Question 14

What is VATER?

Answer 14

Vertebral problems,
Anal anomalies,
Trachea problems,
Esophageal abnormalities, and
Radius or Renal abnormalities

Question 15

In DS infant with duodenal atresia, what is the mother’s pregnancy finding?

Answer 15

Polyhydramnios

Question 16

in DS with duodenal atresia. what is the Upper GI study findings?

Answer 16

double-bubble pattern

Question 17

Cardiac sound of Endocardial cushion defect

Answer 17

loud 1st HS, a wide and fixed split 2nd HS. a low-pitched, mid-diastolic murmur @ LLSB
harsh apical holosystolic murmur in the mitral area

Question 18

ECG findings of AVSD?

Answer 18

superiorly oriented QRS frontal plane axis with counterclockwise depolarization pattern and RVH

Question 19

Pathophysiology of Trisomy 21

Answer 19

Chromosome 21 pair fails to separate, so that one gamete has 2 chromosome 21s and one has none (meiotic non-disjunction). Fertilization of the gamete with two chromosome 21s give rise to a zygote with trisomy 21.

Question 20

Can Trisomy 21 be of paternal origin and why?

Answer 20

Meiotic nondisjunction can occur in spermatogenesis so that the extra copy of chromosome 21 can be of paternal origin.

Question 21

Congenital scan findings in DS fetus.

Answer 21

Nuchal thickening on ultrasound - thickening of the soft tissues at the back of the neck.

Question 22

Pathophysiology of translocation DS

Answer 22

Extra chromosome 21 is joined onto another chromosome (usu 14 , also 15, 22, or 21). This may be present in a phenotypically normal carrier with 45 chromosomes (two being joined together) or in someone with DS and a set of 46 chromosomes but with three copies of chromosome 21 material.

Question 23

Risk of recurrence in translocation DS

Answer 23

mother is translocation carrier : 10-15%
father is translocation carrier: 2.5%
a parent carries 21:21 translocation: all offspring will have DS
neither parent carries translocation: less than 1%

Question 24

Pathophysiology of Mosaic DS

Answer 24

Arises after the formation of the chromosomally normal zygote by nondisjunction at mitosis but can arise by later mitotic nondisjunction in a trisomy 21 conception.

Question 25

NIPT

Answer 25

Noninvasive prenatal testing, in which cell-free fetal DNA is analyzed from maternal blood.

Question 26

Incidence of DS

Answer 26

1.5 per 1000 infants

Question 27

Later medical problems of DS

Answer 27

delayed motor milestones learning difficulties short stature increased susceptibility to infections hearing impairment from secretory OM (75%) visual impairment from cataracts (15%), squints, myopia (50%) leukemia and solid tumours (<1%) acquired hip dislocation and atlantoaxial instability obstructive sleep apnea (50-70%) hypothyroidism (15%) and coeliac disease epilepsy early-onset Alzheimer disease

Question 28

Immediate (at birth) medical complications of DS (2)

Answer 28

Duodenal atresia Congenital heart disease

Question 29

The incidence of trisomy 21 due to nondisjunction is related to maternal age. True or False?

Answer 29

True. All ages - 1 in 650 20 yo - 1 in 1530 30 yo - 1 in 900 35 yo - 1 in 385 37 yo - 1 in 240 40 yo - 1 in 110 44 yo - 1 in 37

Question 30

DS is the most common autosomal trisomy, True or False?

Answer 30

True

Question 31

Fill in the blank: Down Syndrome occurs due to an error in ______ during cell division.

Answer 31

meiosis

Question 32

What is the name of the test that can detect Down Syndrome via amniocentesis?

Answer 32

Fetal Karyotype

Question 33

What type of genetic testing can confirm a diagnosis of Down Syndrome?

Answer 33

Karyotype analysis.

Question 34

Common features in the newborn of DS

Answer 34

hypotonia - 80% poor Moro reflex - 85% hyperflexibility of joints - 80% excess skin on the back of the neck - 80% flat facial profile - 90% slanted palpebral fissures - 80% anomalous auricles - 60% dysplasia of pelvis - 70% dysplasia of phalanx of fifth finger - 60% single palmar crease - 45%

Question 35

Head and Neck findings of DS

Answer 35

flat occiput and third fontanelle round face epicanthic folds brushfield spots in the iris cataracts refractive errors strabismus protruding tongue small ears

Question 36

PE - Hand findings of DS

Answer 36

short metacarpals and phalanges (small and broad hands) transverse palmar crease (45%) fifth finger: hypoplasia or absence of the middle phalanx (60%), clinodactyly (50%), a single crease (40%) hyperextensibility dermatoglyphics - triradius

Question 37

DS Common Associations (17)

Answer 37

duodenal stenosis or atresia pyloric stenosis small bowel atresias hirschsprung's disease anal atresia biliary atresia recurrent respiratory infections hearing impairment from recurrent secretory OM visual impairment from squints or cataracts severe learning difficulties short stature increased risk of leukemia risk of atlantoaxial instability (rare) thyroid disorders (hypothyroidism) Alzheimer's disease Males - hypogonadism and infertility is universal Females - delayed menarche, secondary amenorrhea and premature menopause are common

Question 38

Associated Cardiovascular disorders of DS

Answer 38

AV canal defects (most common) PDA VSD ToF

Question 39

When to repair the cardiac defect?

Answer 39

complete AV septal defects - before age 2 yrs to prevent PHTN partial AVSD - between 2 and 5 years In DS, repair is usually earlier due to increased propensity to develop pulmonary vascular disease

Question 40

Child with DS who has a murmur at LSB and a median sternotomy scar

Answer 40

AVSD or VSD repair with residual VSD. Also, residual left AV valve (i.e. mitral) regurgitation with systolic murmur at the apex