Chromosomal Disorders

Question 1

Turner Syndrome:

Answer 1

Monosomy X
cubitus valgus (outward rotation of forearm at rest), webbed neck, madeulung deformity (wrist dormity, ulna forced out of position), wide spaced nipples, low posterior hairline, lymphadema
cardio: biscuspid aortic valve is most common, but coarctation of aorta is most critical
streak ovaries (amenorrhea), horseshoe kidneys
abdominal ultrasound important; high risk for ovarian tumors

Question 2

Klinefelter syndrome

Answer 2

(XXY)
tall, gynecomastia, wide hips, small testicles, hypogonadism
DD, relatively average IQ
key is fertility preservation
nothing striking seen till puberty

Question 3

22q11 del syndrome

Answer 3

Malar hypoplasia, tubular nose, full eyelids, cleft palate, overfolded ear helix
cardio: interrupted aortic arch, right aortic arch
hypocalcemia
ID, LD, immunodeficiency

Question 4

Triploidy

Answer 4

69,XXY>69,XXX (69,XXY very rare)
>99% lost in 1st trimester, 20% of all chromosomally abnormal miscarriages
3,4 syndactyly, dysplastic calvaria, CHD, holoprosencephaly
If maternal: small placenta, severe IUGR w/ large head
If paternal: large placenta, normal-microcephalic head
dx: elevated AFP, low hCG, low PAPP-A
mechansim (diploid sperm or dispermy most common)

Question 5

Trisomy 18 (edwards syndrome)

Answer 5

Microcephaly, clenched hands w/ overlapping fingers, prominent occiput, rocker bottom feet, thumb/radius hypoplasia,
IUGR, malformed ears, short palpebral fissures
Maternal serum screen: low AFP, hCG, UE3
90% d/t maternal nondisjunction (meiosis 2), 10% d/t mosaicism

Question 6

Trisomy 13 (patau)

Answer 6

Think midline defects! M for midline since 13 is middle of alphabet
Holoprosencephaly, cleft lip/palate, polydactyly, coloboma
severe ID, CHD: fatal within 1st year
75% d/t maternal nondisjunction; 20% d/t translocation, 5% mosaicism
least common of live-born triomies

Question 7

Down Syndrome: Trisomy 21

Answer 7

Cardio defects: AV canal (AV septal defect) is specific, but VSD is most common
upslanting palpebral fissures, single palmar crease, sandal gap deformity, brushfield spots (speckles on iris)
Duodenal atresia, hirschsprung dx
ID, hypotonia, inc. risk of leukemia & alzheimer’s (leukemia risk d/t GATA1 variants)
AML- GATA1 variant; ALL- JAK2 variants
In neonate, if DS is suspected, cardio is most important consult
diagnosis: karyotype (to look for iso 21)
90% d/t maternal nondisjunction (75% meiosis 1)

Question 8

Wolf-Hirschorn Syndrome

Answer 8

: 4p del
del includes WHSC1 and WHSC2
Greek warrior helmet, microcephaly, growth deficiency, ID< seizures, facial assymetry
Cleft lip/palate, CHD, abnormal brain MRI
13% d/t unblanced transclocation

Question 9

Cri-du-Chat:

Answer 9

5p del
cat cry, microcephaly, ID, hypotonia,
cat cry d/t abnormal larynx dev. (only present when del is restricted to 5p15.32)
85% de novo del, 12% due to unbalanced translocation or pericentric inversion

Question 10

Monosomy 1p36

Answer 10

most common terminal del syndrome
hypotonia, DD, microcephaly
short stature, obesity, mild cardio features, cardiomyopathy, SNHL