Chromosomes

Question 1

Chr 11 disorders

Answer 1

Germline:
11p15.5 - imprinting centre:
BWS overgrowth
SRS growth restriction
Emanuel Syndrome der(22)t(11;22)

Somatic:
Ewing sarcoma t(22;11)(q24;q12) EWS-FLI1
Neuroblastoma MYCN (2p24.1), 1p36 del, 11q23 del, 17q dup

Question 2

Beckwith–Wiedemann syndrome – genetic cause and clinical presentation

Answer 2

11p15.5
IC2 hypomethylation of maternal allele
UPD(11)pat
CDKN1C mutations
IC1 hypermethylation

paediatric overgrowth disorder
highly variable phenotype, the hallmark features: gigantism, enlarge tongue, tummy wall defect

85% case are sporadic
Majority cases are mosaic for methylation/UPD(11)pat

Question 3

Silver-Russell syndrome – genetic cause and clinical presentation

Answer 3

growth retardation condition
small, skinny, feeding problems, triangular face, body asymmetry

IC1 hypomethylation of paternal allele at 11p15.5
upd(7)mat
Molecular diagnosis only confirmed in 60% cases

Question 4

Emanuel Syndrome – genetic cause and clinical presentation

Answer 4

der(22)t(11;22)
pre- and postnatal growth deficiency
microcephaly, hypotonia, severe devdel, ear abnormalities , cleft palate, congenital heart defects, kidney abnormalities, and genital abnormalities in males
high mortality assoc with life-threatening congenital malformations

Question 5

What is a risk for a carrier t(11;22) having an offspring with Emanuel syndrome?

Answer 5

Up to 10%

Question 6

Example of recurrent non-Robertsonian translocation

Answer 6

t(11;22)

Question 7

Ewing sarcoma – genetic cause

Answer 7

t(11;22)(q24;q12) EWS-FLI1 EWSR1 ex 1-7 + FLI1 ex 6-9 (or 5-9)

Question 8

Neuroblastoma – genetic abnormalities

Answer 8

MYCN (2p24.1),
1p36 del
11q23 del
17q dup

Question 9

Neuroblastoma – prognostic markers

Answer 9

MYCN amplification,
11q23 deletion and
ploidy level