Chapter 6: Developmental and Genetic Dz

Question 1

A 4-year-old girl presents for a preschool physical examination.
The child has a small head circumference, thin upper lip,
and low-bridge nose. She shows evidence of mild mental
retardation. Her parents state that she is often “emotional.”
Which of the following maternal causes of birth defects most
likely accounts for these clinicopathologic fi ndings?
(A) Alcohol abuse
(B) Cigarette smoking
(C) Congenital syphilis
(D) Inadequate nutrition
(E) Poorly controlled diabetes mellitus

Answer 1

1. Alcohol abuse.

Question 2

A 12-month-old boy is brought to the emergency room for
examination of his right arm following a tumble at home.
Radiologic examination of the limb reveals a recent fracture
of the right ulna and evidence of additional healing fractures.
The child is noted to have blue sclerae. This patient most
likely carries a mutation in a gene that encodes which of the
following proteins?
(A) Collagen
(B) Fibrillin
(C) Keratin
(D) Myosin
(E) Tubulin

Answer 2

2. Collagen.

Question 3

A 28-year-old woman gives birth to a stillborn with a severe
neural tube defect (neonate shown in the image). This birth
defect was caused by an error of morphogenesis that occurred at
which of the following stages of development after fertilization?

Answer 3

3. 20 to 40 days.

Question 4

A 20-year-old man is examined by a new family physician who
discovers numerous pigmented patches and pedunculated
skin tumors on his chest. Biopsy of a tumor discloses a benign
neoplasm derived from Schwann cells. Neither the patient’s
father nor mother shows signs of this disease. This patient
most likely carries a mutation in a gene that encodes which of
the following proteins?
(A) Epidermal growth factor receptor
(B) GTPase activating protein
(C) NF-κB transcription factor
(D) Protein kinase C
(E) Ras protein p21

Answer 4

4. GTPase activating protein.

Question 5

The patient described in Question 4 is at increased risk of
developing which of the following malignant neoplasms?
(A) Ganglioneuroma
(B) Glioblastoma multiforme
(C) Neurofi brosarcoma
(D) Serous cystadenocarcinoma
(E) Squamous cell carcinoma

Answer 5

5. Neurofibrosarcoma.

Question 6

A 25-year-old pregnant woman, at 16 weeks of gestation, visits
her obstetrician. A screening test suggests the possibility of a
neural tube defect in her fetus. An ultrasound examination
shows a 3-cm neural tube defect in the thoracic spine. The
screening test that was administered to the mother measured
serum levels of which of the following proteins?

Answer 6

6. Alpha-fetoprotein (AFP).

Question 7

A 25-year-old man presents for a routine physical examination.
The patient is tall (6 ft, 5 in) and has long fi ngers (shown
in the image). One year later, he suffers a dissecting aortic
aneurysm. This patient most likely carries a mutation in a
gene that encodes which of the following proteins?

Answer 7

7. Fibrillin

Question 8

The genetic disease encountered in the patient described
in Question 7 follows which of the following patterns of
inheritance

Answer 8

8. Autosomal dominant.

Question 9

A 12-month-old boy shows progressive weakness, mental
deterioration, and loss of vision. Laboratory studies
demonstrate decreased activity of hexosaminidase A. The child
eventually becomes blind and dies at 3 years of age. Which
of the following best describes the pathogenesis of neuronal
degeneration in this patient?
(A) Accumulation of unmetabolized substrate
(B) Decreased utilization of metabolic end-product
(C) Formation of an abnormal metabolic end-product
(D) Opening of mitochondrial membrane pore
(E) Synthesis of a novel glycosphingolipid

Answer 9

9. Accumulation of unmetabolized substrate.

Question 10

If the parents of the child described in Question 9 have a total
of four sons and two daughters, then, on average, how many
of their children may be expected to be asymptomatic (i.e.,
silent) carriers of this gene mutation?

Answer 10

10. Three children.

Question 11

A 4-year-old boy is admitted to the hospital with pneumonia
and respiratory distress. The nurses report that the child’s
bowel movements are greasy and have a pungent odor. A sweatchloride
test is positive. Which of the following mechanisms
of disease is the most likely cause of steatorrhea in this child?

Answer 11

11. Lack of pancreatic enzyme secretion.

Question 12

The patient described in Question 11 carries mutations in the
gene that encodes which of the following types of protein?
(A) Membrane ion channel

(E) Receptor tyrosine kinase

Answer 12

12. Membrane ion channel

Question 13

A 10-year-old child presents with xanthomas on the extensor
surfaces of his forearms. Laboratory studies demonstrate a
total serum cholesterol of 820 mg/dL. The child’s mother and
maternal grandfather also have elevated serum cholesterol.
This patient most likely has mutations in the gene that
encodes which of the following proteins involved in lipid
metabolism?
(A) ApoE4
(B) Cholesterol hydroxylase
(C) Chylomicron transport protein
(D) High-density lipoprotein receptor
(E) Low-density lipoprotein receptor

Answer 13

13. Low-density lipoprotein (LDL) receptor.

Question 14

A 10-month-old boy who was adopted from an orphanage
in Eastern Europe presents for a physical examination. His
parents believe that he is failing to meet developmental
milestones. The child is fair skinned and has blond hair. On
physical examination, the patient is noted to have a “mousy”
odor. Laboratory studies demonstrate an inborn error of
amino acid metabolism. To prevent mental retardation, this
patient should be placed on a special diet that lacks which of
the following essential amino acids?

Answer 14

14. Phenylalanine.

Question 15

Which of the following best describes the pathogenesis of
mental retardation in the patient described in Question 14?
(A) Accumulation of unmetabolized substrate
(B) Decreased utilization of metabolic end-product
(C) Formation of an abnormal metabolic end-product
(D) Increased utilization of metabolic end-product
(E) Opening of mitochondrial membrane pore

Answer 15

15. Accumulation of unmetabolized substrate.

Question 16

A 4-year-old boy is found to have extremely pliable skin.
His parents note that he bruises easily. His joints can
be hyperextended. Biochemical studies demonstrate a
defi ciency of lysyl hydroxylase. Ultrastructural examination
of a skin biopsy of this patient would most likely reveal
abnormalities associated with which of the following cell/
tissue components?

Answer 16

16. Collagen fibers.

Question 17

A 25-year-old woman complains of recurrent bone pain and
increasing abdominal girth. Physical examination reveals
massive hepatosplenomegaly. Radiologic studies reveal
several radiolucent bone defects. A bone marrow biopsy
discloses enlarged cells with a fi brillar appearance reminiscent
of “wrinkled tissue paper.” Microscopic examination of a
splenectomy specimen is shown. This patient most likely
carries mutations in the gene that encodes which of the
following types of hydrolytic enzymes?

Answer 17

17. Glucosidase

Question 18

Which of the following best describes the pathogenesis of
hepatosplenomegaly and bone pain in the patient described in
Question 17?
(

Answer 18

18. Accumulation of unmetabolized substrate.

Question 19

A neonate is born with severe motor dysfunction involving
the lower extremities. Radiologic studies show that vertebral
bodies in the lumbar region lack posterior arches. The
vertebral defects are covered by a thin membrane. The space
underneath the membrane contains a mass of tissue that is
composed of meninges and spinal cord. The parents ask for
information regarding risks for similar birth defects in their
future offspring. You mention that dietary supplementation of
the maternal diet has been shown to reduce the incidence of
neural tube defects. What is this substance?

Answer 19

19. Folic acid.

Question 20

The parents of an infant with cleft lip and palate (infant shown
in the image) visit a genetic counselor to discuss the chance
that a similar birth defect will occur in their future offspring. In
addition to teratogen exposure and multifactorial inheritance,
which of the following is an important cause of this error of
morphogenesis?

Answer 20

20. Structural chromosomal abnormality

Question 21

A 4-year-old boy is brought to the physician by his parents
because he tires easily. Physical examination reveals weakness
in the pelvic and shoulder girdles and enlargement of the
child’s calf muscle. Serum levels of creatine kinase are
elevated. A biopsy of calf muscle shows marked variation
in size and shape of muscle fi bers. There are foci of muscle
fi ber necrosis, with myophagocytosis, regenerating fi bers, and
fi brosis. Molecular diagnostic assays would most likely show
alterations in the length of the primary transcript for which of
the following muscle-associated proteins?

Answer 21

21. Dystrophin

Question 22

What will be the likely cause of death in the patient described
in Question 21?
(A) Cardiomyopathy
(B) Cerebrovascular disease
(C) End-stage renal disease
(D) Pulmonary saddle embolism
(E) Respiratory insuffi ciency

Answer 22

22. Cardiomyopathy

Question 23

A 22-year-old man complains about his inability to conceive a
child. On physical examination, the patient is noted to be tall (6 ft, 5 in) and exhibits gynecomastia and testicular atrophy.
Laboratory studies demonstrate increased serum levels of
follicle-stimulating hormone. Cytogenetic studies reveal a
chromosomal abnormality. What is the most common cause
of this patient’s chromosomal abnormality?

Answer 23

23. Meiotic nondisjunction

Question 24

A 35-year-old pregnant woman delivers a baby prematurely at
28 weeks of gestation. Shortly after birth, the neonate becomes
short of breath, with intercostal retraction and nasal fl aring
during respiration. The neonate is placed on a ventilator,
but dies of respiratory insuffi ciency and intraventricular
hemorrhage. Microscopic examination of the lungs at
autopsy is shown. The eosinophilic material lining the air
spaces represents an accumulation of which of the following
proteins?

Answer 24

24. Fibrin

Question 25

If the neonate described in Question 24 had survived, which
of the following would be the most likely complication related
to anoxia and acidosis?

Answer 25

25. Necrotizing enterocolitis.

Question 26

A 16-year-old girl complains that she has not started
menstruating like other girls her age. The patient is short (4
ft, 11 in) and has a thick-webbed neck. Physical examination
reveals widely spaced nipples and poor breast development.
If this patient’s genetic disease was caused by nondisjunction
during mitosis of a somatic cell in the early stages of
embryogenesis, which of the following is the patient’s most
likely karyotype?

Answer 26

26. 45,X/46,XX.

Question 27

A 34-year-old woman in her second pregnancy delivers a female
neonate with severe generalized edema and jaundice. A CBC
of the neonate shows hemolytic anemia. Subsequent workup
of the mother and the newborn reveal an Rh-incompatibility.
Transplacental passage of which of the following proteins is
the principal cause of anasarca and jaundice in this neonate?

Answer 27

27. IgG.

Question 28

The parents of a 2-year-old boy with hyposadias (urethra opens
on the ventral aspect of the penis) visit a genetic counselor to
discuss the chances that a similar birth defect will occur in
their future offspring. This birth defect shows which of the
following patterns of inheritance?

Answer 28

28. Multifactorial.

Question 29

A 42-year-old woman gives birth to a neonate with multiple
congenital abnormalities. Physical fi ndings included a fl at
facial profi le, slanted eyes, epicanthal folds, Brushfi eld spots,
short nose, short neck, dysplastic ears, clinodactyly, a large
protruding tongue, and a pronounced heart murmur. What is
the most common cause of this developmental birth disease?

Answer 29

29. Nondisjunction.

Question 30

As an adult, the brain of the patient described in Question 29
will show histopathologic changes that are seen in patients
with which of the following neurologic diseases?

Answer 30

30. Alzheimer disease.

Question 31

50-year-old man with a history of type 2 diabetes mellitus
asks about the chances that his children will inherit this metabolic
disorder. The patient is told that he has a genetic disease that
shows which of the following patterns of inheritance?

Answer 31

31. Multifactorial

Question 32

A 25-year-old man with a history of autism and mental
retardation is seen by a genetic counselor. The man has
coarse facial features, an increased head circumference, and
macro-orchidism. His maternal uncle is similarly affected.
After further evaluation, a diagnosis of fragile X syndrome
is rendered. What is the most likely underlying cause of this
patient’s genetic disease?

Answer 32

32. Expansion of trinucleotide repeat.

Question 33

A 28-year-old man presents to the emergency room 1 hour
after experiencing crushing substernal chest pain. Laboratory
studies and ECG confi rm the diagnosis of acute myocardial
infarction. The patient dies 24 hours later of cardiac arrhythmia.
This patient most likely had which of the following genetic
diseases?

Answer 33

33. Familial hypercholesterolemia.

Question 34

A 5-year-old boy presents with a maculopapular rash. On
physical examination, the rash affects the palms and soles.
Cracks and fi ssures are noted around the mouth and anus.
There is funduscopic evidence of interstitial keratitis. Mild
hepatosplenomegaly is present. The anterior tibial bones
exhibit an outward curvature. What is the most likely etiology
of these clinicopathologic fi ndings?

Answer 34

34. Syphilis

Question 35

A 3-year-old boy dies in an automobile accident. At autopsy,
the right lung is markedly shrunken. Dissection shows that
the right main stem bronchus ends blindly in nondescript
tissue composed of rudimentary ducts and connective tissue.
This fi nding represents an example of which of the following
errors of morphogenesis?

Answer 35

35. Aplasia.

Question 36

The mother of a newborn boy is alarmed that her baby
regurgitates at every feeding. An endoscopic examination
reveals that the child’s esophagus is almost completely
occluded. This fi nding represents an example of which of the
following errors of morphogenesis?

Answer 36

36. Atresia.

Question 37

An 87-year-old woman dies peacefully in her sleep. At autopsy,
a rest of pancreatic tissue is identifi ed in the wall of the lower
esophagus. This fi nding represents an example of which of the
following congenital tumor-like conditions?

Answer 37

37. Choristoma

Question 38

A 30-year-old pregnant woman visits her obstetrician for prenatal
care and eventual delivery. The patient volunteers that two of
her three children had “yellow jaundice” at birth. Her youngest
girl had been severely jaundiced and had been given two blood
transfusions. Prenatal laboratory tests indicate that the mother is
blood type O, Rh negative, whereas her husband is blood type A,
Rh positive. The obstetrician samples amniotic fl uid at 36 weeks
of gestation to ascertain whether the fetus is mature enough for
preterm delivery. Quantitative analysis of which of the following
was most likely used as an indicator of fetal lung maturity?

Answer 38

38. Lecithin

Question 39

The patient described in Question 38 delivers a female at 37
weeks of gestation with evidence of severe generalized edema
(neonate shown in the image). The baby is given exchange
transfusions with Rh-negative cells but subsequently dies.
Which of the following best describes the pathogenesis of
anasarca in this baby?

Answer 39

39. Congestive heart failure

Question 40

An 18-year-old woman delivers a male neonate following a
diffi cult labor and delivery (dystocia). The baby appears
vigorous at birth (Apgar score = 9), but a cephalohematoma
is apparent 2 hours later. A CT scan of the baby’s head shows
subperiosteal hemorrhage over one of the calvarial bones.
What is the most likely outcome of this complication of labor
and delivery?

Answer 40

40. Spontaneous resolution.

Question 41

A 42-year-old woman in her third pregnancy delivers a female
neonate at 30 weeks of gestation. The baby develops jaundice
within 2 days. The unconjugated serum bilirubin is 15 mg/dL.
Which of the following is the most serious complication of
untreated hyperbilirubinemia in this neonate?

Answer 41

41. Encephalopathy.

Question 42

A 27-year-old woman presents for a pregnancy test. She
recalls drinking heavily during the week in which she may
have conceived. What is the most likely consequence of toxic
exposure to the conceptus during early (preimplantation)
development?

Answer 42

42. Embryonic lethality.