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Chapter 11
Cytogenetic Disorders
115
FIGURE 11-3. Numerical chromosomal abnormalities (aneuploidy). (A,B) Trisomy 13 (Patau syndrome).
The key features
of Trisomy 13 are microcephaly with sloping forehead, scalp defects, microphthalmia, cleft lip and palate, polydactyly, fin-
gers flexed and overlapping, and cardiac malformations. (C,D) Trisomy 18 (Edwards syndrome). The key features of
Trisomy 18 are low birth weight, lack of subcutaneous fat, prominent occiput, narrow forehead, small palpebral fissures,
low-set and malformed ears, micrognathia, short sternum, and cardiac malformations. (E,F,G) Trisomy 21 (Down syn-
drome). (E,F)
Photographs of a young child and boy with Down syndrome. Note the flat nasal bridge, prominent epicanthic
folds, oblique palpebral fissures, low-set and shell-like ears, and protruding tongue. Other associated features include:
generalized hypotonia, transverse palmar creases (simian lines), shortening and incurving of the fifth fingers (clin-
odactyly), Brushfield spots, and mental retardation. (G) Photograph of hand in Down syndrome showing the simian crease.
(H) Klinefelter syndrome (47,XXY).
Photograph of a young man with Klinefelter syndrome. Note the hypogonadism,
eunuchoid habitus, and gynecomastia. (I,J) Turner syndrome (45,X). Photograph of a 3-year-old girl with Turner syndrome.
Note the webbed neck due to delayed maturation of lymphatics, short stature, and broad shield chest.
p
15
5
5p15
deletion
16
p
4
4p16
deletion
13
11
15
15
Paternal
Maternal
q
15q11-13
microdeletion
C
D
13
11
q
15q11-13
microdeletion
A
B
FIGURE 11-4. Structural chromosomal abnormalities (deletion/microdeletions) (A)
Chromosome 4p deletion (Wolf-
Hirschhorn syndrome). The deletion at 4p16 is shown on chromosome 4. A photograph of a 5-year-old boy with Wolf-
Hirschhorn syndrome showing a prominent forehead and broad nasal root (“Greek warrior helmet”), short philtrum,
down-turned mouth, and severe mental retardation (IQ
20). (B) Chromosome 5p deletion (Cri du chat; cat cry syndrome).
The deletion at 5p15 is shown on chromosome 5. A photograph of an infant with Cri du chat showing round facies, micro-
cephaly, and mental retardation. (C) Prader-Willi syndrome. The microdeletion at 15q11-13 is shown on chromosome 15
inherited from the father (paternal). A photograph of a 10-year-old boy with Prader-Willi syndrome showing hypogo-
nadism, hypotonia, obesity, short stature, and small hands and feet. (D) Angelman syndrome (happy puppet syndrome).
The microdeletion at 15q11-13 is shown on chromosome 15 inherited from the mother (maternal). A photograph of a young
woman with Angelman syndrome showing a happy disposition with inappropriate laughter and severe mental retardation
(only 5 to 10 word vocabulary. (continued)
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B
A
FIGURE 11-5. Translocations. (A) Acute promyelocytic leukemia t(15;17)(q21;q21).
The translocation between chromo-
somes 15 and 17 is shown. A photomicrograph of acute promyelocytic leukemia showing abnormal promyelocytes with
their characteristic pattern of heavy granulation and bundle of Auer rods. (B) Chronic myeloid leukemia t(9;22)(q34;q11).
The translocation between chromosomes 9 and 22 is shown. A photomicrograph of chronic myeloid leukemia showing
marker granulocytic hyperplasia with neutrophilic precursors at all stages of maturation. Erythroid (red blood cell) pre-
cursors are significantly decreased with none shown in this field.
11
22
17
q
13
p
22q11
microdeletion
17p13
microdeletion
E
F
q
(continued) (E) DiGeorge syndrome. The microdeletion at 22q11 is shown on chromosome 22. A photomi-
crograph of a young infant with craniofacial defects (e.g., hypertelorism, microstomia) along with partial or complete
absence of the thymus gland. (F) Miller-Dieker syndrome (agyria, lissencephaly). The microdeletion at 17p13.3 is shown
on chromosome 17. MRI (top figure) shows a complete absence of gyri in the cerebral hemispheres. The lateral ventricles
are indicated by the arrows. A photograph of a young girl with Miller-Dieker syndrome showing small, anteverted nose,
long philtrum, and thin prominent upper lip.
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Chapter 11
Cytogenetic Disorders
117
A
B
C
D
E
F
G
FIGURE 11-6. Chromosome breakage.
(A,B) Xeroderma pigmentosa (C,D,E) Ataxia-telangiectasia (F) Fanconi syndrome
(G) Bloom syndrome.
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118
1.
Which of the following patients should be
offered cytogenetic studies?
(A)
parents of a child with trisomy 21
(B)
parents of a child with Turner syndrome
(C)
a 37-year-old woman who is pregnant
(D)
parents of a normal child
2.
Amniocentesis is performed on a patient
at 16 weeks’ gestation because of her age
(she is 36). The final report to the physician
says that the fetus has a 45X/46,XX kary-
otype, with the 45,X cell line making up 90%
of the cells examined. The fetus will most
likely have phenotypic features of which of
the following syndromes?
(A)
Fragile X syndrome
(B)
Turner syndrome
(C)
Down syndrome
(D)
Angelman syndrome
3.
Which of the following is one of the most
common causes of Prader-Willi syndrome?
(A)
a microdeletion on the maternal chro-
mosome 15
(B)
a microdeletion on the paternal chromo-
some 15
(C)
a microdeletion on the maternal chro-
mosome 22
(D)
a microdeletion on the paternal chromo-
some 22
4.
Which one of the following Robertsonian
translocation carriers has the greatest risk of
having an abnormal child?
(A)
45,XX,t(14;15)
(B)
45,XY,t(15;22)
(C)
45,XX,t(13;21)
(D)
45,XY,t(14;22)
5.
Which of the following is the main risk to
children of inversion carriers?
(A)
Down syndrome
(B)
duplications or deletions
(C)
chronic myelogenous leukemia
(D)
Robertsonian translocations
6.
Which one of the following is an indica-
tion that you should offer a patient cytoge-
netic studies?
(A)
family history of Huntington disease
(B)
family history of unexplained miscar-
riages and mental retardation
(C)
family history of tall stature
(D)
family history of cystic fibrosis
7.
A tall male with gynecomastia and small
testes should have a cytogenetic study to
rule out which of the following?
(A)
XYY syndrome
(B)
Klinefelter syndrome
(C)
Fragile X syndrome
(D)
Turner syndrome
8.
A woman comes to clinic because of her
family history of tetralogy of Fallot (a
conotruncal heart defect). Her father was
born with a heart defect, has immunity
problems, and schizophrenia. Her brother
has cleft palate and a heart defect as well.
The patient was studied cytogenetically and
found to have a microdeletion of 22q11.2 by
FISH. What is the best estimate of her recur-
rence risk for a future pregnancy?
(A)
2%–3%
(B)
5%–6%
(C)
10%
(D)
50%
(E)
100%
9.
You see a 4-year-old boy in clinic whom
you believe has Prader-Willi syndrome. You
request cytogenetic studies and the child is
found to have an unbalanced 14;15 translo-
cation. Fluorescent in situ hybridization
(FISH) confirms that the Prader-Willi/
Angelman area on chromosome 15 is deleted.
You request cytogenetic studies of the par-
ents and one of them is found to have a bal-
anced translocation. Which of the following
are the most likely cytogenetic findings?
(A)
The father has a balanced 14;15 translo-
cation.
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Chapter 11
Cytogenetic Disorders
119
(B)
The father’s Prader-Willi/Angelman locus
is found by FISH to be deleted.
(C)
The mother has a balanced 14;15 translo-
cation.
(D)
The mother’s Prader-Willi/Angelman
locus is found by FISH to be deleted.
10.
Which of the following is the most com-
mon cause of Down syndrome?
(A)
Robertsonian translocations
(B)
21;21 balanced reciprocal translocation
(C)
nondisjunction in mitosis
(D)
nondisjunction in meiosis
11.
A chromosome deletion results in which
of the following?
(A)
a chromosome monosomic for the
deleted area
(B)
a chromosome disomic for the deleted
area
(C)
a chromosome trisomic for the deleted
area
(D)
a chromosome tetrasomic for the deleted
area
12.
In the 9;22 translocation characteristic of
chronic myeloid leukemia (CML), the
Philadelphia chromosome has which of the
following characteristics?
(A)
It is deleted for the abl proto-oncogene.
(B)
It is deleted for the bcr proto-oncogene.
(C)
It has the abl/bcr fusion gene generated
by the 9;22 translocation.
(D)
It is deleted for the abl/bcr fusion gene.
13.
Jane and her husband Charlie have a
phenotypically normal female child with a
balanced Robertsonian translocation
between chromosomes 13 and 21. How
many chromosomes does the child have?
(A)
46
(B)
47
(C)
45
(D)
48
14.
Jane and Charlie from question 13 wish
to have more children. What should their
physician recommend as their next course of
action?
(A)
Recommend that they have no more
children because of the risk of having an
abnormal child.
(B)
Recommend that Jane be studied to
determine if she is a carrier of the
Robertsonian translocation.
(C)
Recommend that Charlie be studied to
determine if he is a carrier of the
Robertsonian translocation.
(D)
Recommend that both Jane and Charlie
be studied to determine if one of them is
a carrier of the Robertsonian transloca-
tion.
15.
The greatest risk of having a child with a
chromosome abnormality will occur with
which one of the following?
(A)
a couple who had a child with a de novo
(spontaneously occurring) unbalanced
translocation between chromosomes 2
and 5
(B)
a couple who had a child with an unbal-
anced translocation between chromo-
somes 2 and 5, and the father was identi-
fied as a carrier of a balanced 2;5
translocation
(C)
a couple who had a child with Down syn-
drome
(D)
a couple who have had no children
16.
Which of the following karyotypes is
most likely to result in a viable (capable of
being born alive) outcome?
(A)
47,XYY
(B)
47,
16
(C)
69,XXX
(D)
47,XY,
18
17.
Which of the following is the best esti-
mate of the chance that a child produced by
the union of a female carrier of a 21;21
Robertsonian translocation carrier and a
karyotypically normal male will have Down
syndrome?
(A)
0%
(B)
5%
(C)
15%
(D)
100%
18.
A nondisjunction of chromosome 21 in
meiosis II in a male would yield which com-
bination of the following gametes?
(A)
one sperm with two chromosome 21s,
the rest with one
(B)
one sperm with no 21s, three with two
21s
(C)
one sperm with two chromosome 21s,
one with no chromosome 21s and two
sperm with one chromosome 21
(D)
all of the sperm would have one chromo-
some 21
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